Multiple Myeloma: Phase 3 Study of DARZALEX + VMP Reduced Risk of Disease Progression and Mortality

MedicalResearch.com Interview with:

Dr. Meletios A. Dimopoulos MD Professor and Chairman Department of Clinical Therapeutics University Athens School of Medicine Athens, Greece

Dr. Dimopoulos

DrMeletios A. Dimopoulos MD
Professor and Chairman
Department of Clinical Therapeutics
University Athens School of Medicine
Athens, Greece

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Updated data from the Phase 3 POLLUX trials showed DARZALEX, in combination with lenalidomide and dexamethasone, reduced the risk of disease progression or death by 56 percent, compared to lenalidomide and dexamethasone alone (Hazard Ratio [HR]=0.44; 95 percent CI [0.34-0.55], p<0.0001). After a median follow-up of 32.9 months, the median progression-free survival (PFS) in the DARZALEX arm has not been reached, compared with a median PFS of 17.5 months for patients who received lenalidomide and dexamethasone alone.

DARZALEX in combination with lenalidomide and dexamethasone also significantly increased the overall response rate (ORR) compared to lenalidomide and dexamethasone alone (93 percent vs. 76 percent, p<0.0001), including rates of complete response (CR) or better (55 percent vs. 23 percent, p<0.0001). DARZALEX also showed significantly higher (>3-fold) MRD-negative rates compared to lenalidomide and dexamethasone alone. These data were featured as an oral presentation (Abstract #739) at the 59th American Society of Hematology (ASH) Annual Meeting in early December.

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Older Diabetes Drug Metformin May Resensitize Tumors to Chemotherapy

MedicalResearch.com Interview with:

Terra G Arnason, MD PhD, Associate Professor, Division of Endocrinology, Department of Medicine University of Saskatchewan Saskatoon, SK, Canada 

Dr. Arnason

Terra G Arnason, MD PhD, Associate Professor,
Division of Endocrinology,
Department of Medicine
University of Saskatchewan
Saskatoon, SK, Canada

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Response: Metformin has been used worldwide for decades to treat Type diabetes.

Metformin is a cheap non-toxic compound that was originally plant derived. In the past decade a number of meta-analyses have demonstrated that Type 2 individuals taking
metformin have a reduced risk of developing many different cancers and do better
longterm. The molecular events facilitating metformin’s activity remain obscure and
it is unknown whether metformin can help cancer patients avoid the development of
drug resistant cancers years after successful treatment.

In our study we asked whether metformin can not only restore sensitivity of multiple drug resistant tumors to chemotherapy once again, but whether metformin can prevent the development of multiple drug resistance in the “rst place. We demonstrate that metformin can sensitize drug resistant cells to chemotherapy once again, which supports recent
studies, but we also show for the “first time that Metformin can prevent the
progression of cancer cells towards drug resistance using cell culture experiments.

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Thinking Abilities May Decline After Treatment For Head and Neck Cancers

MedicalResearch.com Interview with:

Lori J Bernstein, PhD, CPsych Neuropsychologist, Dept. of Supportive Care Core Member, Cancer Rehabilitation & Survivorship Program ELLICSR Centre for Health Wellness and Cancer Survivorship Princess Margaret Cancer Centre, UHN Clinical Research Unit Member, Princess Margaret Research Institute Assistant Professor, Dept. of Psychiatry, Faculty of Medicine University of Toronto Adjunct Faculty, Graduate Program in Psychology, York University

Dr. Bernstein

Lori J Bernstein, PhD, CPsych
Neuropsychologist, Dept. of Supportive Care
Core Member, Cancer Rehabilitation & Survivorship Program
ELLICSR Centre for Health Wellness and Cancer Survivorship
Princess Margaret Cancer Centre, UHN
Clinical Research Unit Member,
Princess Margaret Research Institute
Assistant Professor, Dept. of Psychiatry, Faculty of Medicine
University of Toronto
 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Despite the increasing role of (chemo-)radiation treatment for head and neck cancer (HNC), and involvement of central nervous system structures in the radiation field, we don’t know a lot about whether there are short or long term consequences in thinking abilities in survivors. So our question was this: Do people treated for head and neck cancer with radiation or chemoradiation have short or long term neurocognitive deficits after treatment?

We assessed head and neck cancer patients and healthy non-cancer controls four times, first at baseline (after diagnosis but before treatment), and then again 6, 12, and 24 months later. We found that compared to the controls, patients decline over time in several different neurocognitive domains, including concentration, verbal memory, and executive function. We found that as many as 38% of patients suffered from impaired global neurocognitive functioning by two years after treatment compared to none of the controls.

MedicalResearch.com: What should clinicians and patients take away from your report?

Response: The findings indicate that some (but not all) head and neck cancer survivors are at risk of suffering from declines in thinking abilities such as attention and memory. These changes can be subtle and increase gradually. We didn’t follow people beyond 2 years after treatment, so we don’t know whether these deficits would improve, worsen, or stabilize after that.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: Longer longitudinal follow-up is needed to determine if symptoms change after 2 years. More investigation of the relationships between treatment variables such as radiation dosing and long term neurocognitive function is important. Further research is also needed to find ways to avoid, reduce and compensate for declines.

MedicalResearch.com: Is there anything else you would like to add?

Response: We are extremely grateful to the people who participated in this study. We plan to reassess participants for several more years, so we hope to know more about even longer term cognitive function in people treated for head and neck cancer. In addition, I want to acknowledge that we could not have done this work without the support of the Princess Margaret Cancer Foundation and The Canadian Institutes of Health Research.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Alona Zer, Gregory R. Pond, Albiruni R. Abdul Razak, Kattleya Tirona, Hui K. Gan, Eric X. Chen, Brian O’Sullivan, John Waldron, David P. Goldstein, Ilan Weinreb, Andrew J. Hope, John J. Kim, Kelvin K. W. Chan, Andrew K. Chan, Lillian L. Siu, Lori J. Bernstein. Association of Neurocognitive Deficits With Radiotherapy or Chemoradiotherapy for Patients With Head and Neck Cancer. JAMA Otolaryngol Head Neck Surg. Published online November 22, 2017. doi:10.1001/jamaoto.2017.2235

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

 

 

 

 

 

 

Medical Tetrahydrocannabinol May Be Beneficial For Seizures and Chemotherapy Side Effects

MedicalResearch.com Interview with:

Dr. Wong

Dr. Wong

Shane Shucheng Wong, MD
Massachusetts General Hospital
Boston, Massachusetts 

MedicalResearch.com: What is the background for this study?

Response: Medical cannabis is now legal in 29 states and the District of Columbia, and in those areas with active programs, children and adolescents can legally access medical cannabis with certification from their doctor and consent from a parent. This means that doctors and families need to understand what we know and what we don’t yet know about medical cannabis in order to make the best decision for the health of the individual child. Two synthetic cannabinoids – compounds that act on specific receptors in the brain – have been approved for medical use in the U.S., both of which mimic a form of THC (tetrahydrocannabinol), the compound responsible for the “high” of recreational cannabis use. Dronabinol (Marinol) is approved to treat chemotherapy-induced nausea and vomiting in both children and adults, while the pediatric use of nabilone (Cesamet) carries a caution. A third cannabinoid, cannabidiol, is currently in phase 3 trials for treatment of seizures.

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Patients With Dementia Less Likely To Receive Chemotherapy for Colon Cancer

MedicalResearch.com Interview with:

Yingjia Chen, M.Sc, MPH, Ph.D. Postdoctoral Fellow University of California, San Francisco

Dr. Chen

Yingjia Chen, M.Sc, MPH, Ph.D.
Postdoctoral Fellow
University of California, San Francisco 

MedicalResearch.com: What is the background for this study?

Response: Both colon cancer and dementia are prevalent among the elderly and have a high risk of co-occurrence. Previous studies found that patients with dementia were treated less aggressively. In this study, we hypothesized that presence of pre-existing dementia was associated with worse survival for stage III colon cancer patients, and that post-operative chemotherapy was on the causal pathway.

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Some Breast Cancer Patients With Complete Response To Neoadjuvant Therapy Can Avoid Further Surgery

MedicalResearch.com Interview with:

Audree Tadros, MD, MPH Chief Administrative Fellow, Breast Surgical Oncology Training Program Department of Breast Surgical Oncology MD Anderson Cancer Center and

Dr. Tadros

Audree Tadros, MD, MPH
Chief Administrative Fellow, Breast Surgical Oncology Training Program
Department of Breast Surgical Oncology
MD Anderson Cancer Center and

Henry M. Kuerer, MD, PhD, FACS Executive Director, Breast Programs MD Anderson Cancer Network PH and Fay Etta Robinson Distinguished Professor in Cancer Research Department of Breast Surgical Oncology Director, Breast Surgical Oncology Training Program

Dr. Kuerer

Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Cancer Research
Dept of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program

MedicalResearch.com: What is the background for this study?

Response: Neoadjuvant chemotherapy (NCT) has the ability to confer a pCR (pathologic complete response-when no residual cancer is found) in both the breast and axillary lymph nodes. We know that this is most likely to occur in women with HER2 positive and triple negative disease. The high rate of pCR among these patients raises the question of whether surgery is still required, particularly among those who will receive adjuvant radiation therapy.

Until recently, we lacked the ability to pre-operatively predict patients who achieved a breast pCR. Recently, we completed a clinical feasibility trial examining the ability of image-guided biopsy to predict a pCR after neoadjuvant chemotherapy. Our biopsy technique was able to accurately predict a pCR in 98% of patients with only a 5% false negative rate. Based upon these findings, we believe we can accurately determine which patients achieve a breast pCR. This led us to develop a clinical trial to see if breast surgery is redundant in patients who achieve a pCR. An important question that remained was if we are going to omit breast surgery in these exceptional responders, can we also omit axillary surgery?

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For African American Women, Breast Cancer Symptoms Worsen During Initial Treatments

MedicalResearch.com Interview with::

Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN Acute and Tertiary Care Department University of Pittsburgh School of Nursing

Margaret Rosenzweig

Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN
Acute and Tertiary Care Department
University of Pittsburgh School of Nursing

MedicalResearch.com: What is the background for this study?

Response: A significant survival disparity still exists between African American and non-Hispanic white women diagnosed with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The current study was a secondary, exploratory aim from the Attitudes, Communication, Treatment, and Support (ACTS) Intervention to Reduce Breast Cancer Treatment Disparity study, which is a randomized controlled trial of a psychoeducational intervention to encourage acceptance and adherence to chemotherapy compared with usual care for  African American women with breast cancer. The purpose of the current study was to:

1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and

2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe.

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Diabetes Drug May Enhance Melanoma Chemotherapy

MedicalResearch.com Interview with:

Bin Zheng, PhD Assistant Professor Cutaneous Biology Research Center Massachusetts General Hospital Harvard Medical School Charlestown, MA 02129

Dr. Bin Zheng

Bin Zheng, PhD
Assistant Professor
Cutaneous Biology Research Center
Massachusetts General Hospital
Harvard Medical School
Charlestown, MA 02129 

MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Melanoma is the most deadly form of skin cancer with more than 75,000 newly diagnosed cases in the US each year. Over the years, various genetic driver mutations have been identified that cause melanoma, including mutations in the genes BRAF and NRAS. Recent genetic insights into the development of melanoma showed that also mutations in NF1 can lead to melanoma. While there are targeted therapies available for BRAF-mutant melanoma, thus far no such therapies are available for NF1-mutant melanoma. We identified that using a combination of an ERK inhibitor, SCH772984, and the antidiabetic drug phenformin could provide a novel therapeutic strategy for NF1-mutatnt melanomas.

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ER-beta May Identify Breast Cancer Patients For Whom Chemotherapy is Sufficient

MedicalResearch.com Interview with:
Helena Jernström, PhD
Associate Professor in Experimental Oncology
Study Coordinator for Graduate studies Division of Oncology and Pathology
Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University
Division of Oncology and Pathology, Department of Clinical Sciences, Lund
Lund University Cancer Center/Kamprad
Lund, Sweden

MedicalResearch.com: What is the background for this study?

Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated.

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Predictors of Chemosensitivity in Triple Negative Breast Cancer

MedicalResearch.com Interview with:

Christos Hatzis, PhD Assistant Professor of Medicine Director of Bioinformatics, Breast Medical Oncology Yale Comprehensive Cancer Center Yale School of Medicine New Haven, CT

Dr. Christos Hatzis,

Christos Hatzis, PhD
Assistant Professor of Medicine
Director of Bioinformatics, Breast Medical Oncology
Yale Comprehensive Cancer Center
Yale School of Medicine
New Haven, CT

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Triple negative breast cancer (TNBC) is a highly heterogeneous and aggressive disease, and although no effective targeted therapies are available to date, about one-third of patients with TNBC achieve pathologic complete response (pCR) from standard-of-care anthracycline/taxane (ACT) chemotherapy. The heterogeneity of these tumors, however, has hindered the discovery of effective biomarkers to identify such patients.

Identifying chemosensitive triple negative breast cancers could significantly impact
the survival of patients with these difficult to treat cancers until novel targeted
therapies become available. We hypothesized that genomic somatic aberrations may
provide important molecular clues about chemosensitivity in TNBC. Our study used
a carefully selected cohort of 29 uniformly treated TNBC patients who either achieved
pathologic complete response (pCR) or had extensive residual disease after neoadjuvant
anthracycline/taxane chemotherapy.

MedicalResearch.com: What are the main findings?

Response: We sequenced the coding genomic DNA of TNBC tumors and compared the somatic mutations found in the two groups at the two extremes of the chemosensitivity spectrum.

Our analysis revealed that, although mutations in single genes were not individually predictive, TNBC tumors bearing mutations in genes involved in the androgen receptor
(AR) and FOXA1 pathways were much more sensitive to chemotherapy.
We also found that mutations that lowered the levels of functional BRCA1 or BRCA2 RNA
were associated with significantly better survival outcomes; we derived a BRCA
deficiency signature to define this new, highly chemosensitive subtype of TNBC.
BRCA-deficient TNBC tumors have a higher rate of clonal mutation burden, defined as
more clonal tumors with a higher number of mutations per clone, and are also associated
with a higher level of immune activation, which may explain their greater chemosensitivity.

MedicalResearch.com: What should readers take away from your report?

Response: Mutations in the AR/FOXA1 pathway provide a novel marker for identifying chemosensitive TNBC patients who may benefit from current standard-of-care chemotherapy regimens.

The newly defined RNA-based BRCA-deficient subtype includes up to 50% of the
Triple negative breast cancer tumors that appear to be immune primed, and it would be of interest to investigate combinations of chemotherapy with immunotherapies, which could provide clinical benefit for these patients. Although our study showed concordant results in three different datasets, our key findings need to be further validated in a larger, prospectively designed study with archival samples.

MedicalResearch.com: What recommendations do you have for future research as a result of this study?

Response: The comprehensive molecular analysis presented in this study directly links BRCA deficiency with increased clonal mutation burden and significantly enhanced chemosensitivity in Triple negative breast cancer and suggests that functional RNA-based BRCA deficiency needs to be further examined in TNBC. Our results suggest that the combination of immunotherapies with ACT chemotherapy or PARP inhibitors might be an effective strategy for treating BRCA-D tumors.

The strong connection of ACT chemosensitivity and immune activity with a new transcriptionally defined BRCA-D phenotype could help inform future therapeutic strategies for TNBC patients.

MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.

Citation:

Predictors of Chemosensitivity in Triple Negative Breast Cancer: An Integrated Genomic AnalysisTingting Jiang,Weiwei Shi,Vikram B. Wali,Lőrinc S. Pongor,Charles Li,Rosanna Lau,Balázs Győrffy,Richard P. Lifton,William F. Symmans,Lajos Pusztai,Christos Hatzis

PLOS Medicine Published: December 13, 2016http://dx.doi.org/10.1371/journal.pmed.1002193

Note: Content is Not intended as medical advice. Please consult your health care provider regarding your specific medical condition and questions.

More Medical Research Interviews on MedicalResearch.com

Breast Cancer: PARP Inhibitor Veliparib Has Potential To Enhance Platinum Chemotherapy in Recurrent or Metastatic Disease

MedicalResearch.com Interview with:
Vince Giranda, M.D., PH.D.
Project Director
AbbVie Oncology Development

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: In this Phase 2 study, called BROCADE 2, veliparib combined with the platinum chemotherapy regimen carboplatin and paclitaxel showed positive trends in overall survival (OS) and progression-free survival (PFS), although these were not statistically significant. Importantly there were no meaningful increase in side effects with the addition of veliparib to carboplatin and paclitaxel. The veliparib combination regimen also demonstrated a significantly higher objective response rate.

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Low-Dose Regularly Timed Chemotherapy May Keep Some Resistant Cancers in Check

MedicalResearch.com Interview with:

Kelvin K. Tsai, MD, PhD Associate Investigator and Attending Physician Laboratories for Tumor Aggressiveness and Stemness National Institute of Cancer Research, National Health Research Institutes Associate Professor and Principal Investigator Laboratories of Advanced Molecular Therapeutics Graduate Institute of Clinical Medicine College of Medicine, Taipei Medical University, Taiwan

Dr. Kelvin K. Tsai

Kelvin K. Tsai, MD, PhD
Associate Investigator and Attending Physician
Laboratories for Tumor Aggressiveness and Stemness
National Institute of Cancer Research, National Health Research Institutes
Associate Professor and Principal Investigator
Laboratories of Advanced Molecular Therapeutics
Graduate Institute of Clinical Medicine
College of Medicine, Taipei Medical University, Taiwan

MedicalResearch.com: What is the background for this study?

Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers.

We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated.

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How Does Tailoring Chemotherapy Affect Breast Cancer Survival?

MedicalResearch.com Interview with:
Jonas Bergh M.D, Ph.D. F.R.C.P. (London, UK)
Professor of Oncology (Mimi Althainz´donation)
Director Strategic Research Program in Cancer
Karolinska Institutet
Radiumhemmet, Karolinska University Hospital
Stockholm, Swede

MedicalResearch.com: What is the background for this study?

Response: Present standard dosing of chemotherapy is aiming at a similar dose for each individual (similar effects and side-effects) , by calculating the dose per mg/m2 based on a formula originally established by du Bois (1916), based on body surface calculations by measuring height and weight. As I recall it, this was done on nine individuals…
However, the body surface has very little to do with how you cytotoxic drugs are metabolized and excreted… in practice this means that chemotherapy dosing based on body surface area will result in under- or overdosing of quite a proposition of the patients… Please Google/run a PubMed research on H. Gurney in Australia, he and other have really expressed their concerns with our present chemotherapy dosing strategies.

In our prospective adjuvant chemotherapy study of high risk breast cancer patients we tested a very well established standard chemotherapy regimen given every third week (FEC100 mg/m2 x 3+ docetaxel 100 mg/m2 x3) vs. our experimental arm given very second week in a dose dense fashion. We also tried to optimize the dosing, aiming at avoiding overdosing some patients at the first course and increase the dose for those without predefined toxicities. Therapy duration was similar in both groups, 15 weeks. Please see the end of the discussion in JAMA for the shortcomings with our study.

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Antiemetic Drugs Can Be Overprescribed To Chemotherapy Patients

MedicalResearch.com Interview with:
Ayako Okuyama, RN, PHN, MW, PhD
Center for Cancer Control and Information Services
National Cancer Center, Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Chemotherapy-induced nausea and vomiting (CINV) is a major concern for chemotherapy patients. Despite widespread concern, not all chemotherapeutic drugs cause severe CINV. Our study illustrated that the potential for overuse of prophylactic antiemetics for chemotherapy with minimal and low emetic risks according to the antiemetic guidelines.

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Localized Prostate Cancer: Patient-Reported Outcomes after Monitoring, Surgery, or Radiotherapy

MedicalResearch.com Interview with:

Professor Jenny Donovan  PhD   OBE FMedSci NIHR-SI AcSS FFPHM Director, NIHR CLAHRC West (National Institute for Health Research Collaboration for  Leadership in Applied Health Research and Care West) at University Hospitals Bristol NHS Trust Bristol, UK

Prof. Jenny Donovan

Professor Jenny Donovan  PhD
OBE FMedSci NIHR-SI AcSS FFPHM
Director, NIHR CLAHRC West
(National Institute for Health Research Collaboration for
Leadership in Applied Health Research and Care West)
at University Hospitals Bristol NHS Trust
Bristol, UK

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: PSA testing identifies many men with prostate cancer, but they do not all benefit from treatment. Surgery, radiation therapy and various programs of active monitoring/surveillance can be given as treatments for fit men with clinically localized prostate cancer. Previous studies have not compared the most commonly used treatments in terms of mortality, disease progression and patient-reported outcomes. In the ProtecT study, we used a comprehensive set of validated measures, completed by the men at baseline (before diagnosis), at six and 12 months and then annually for six years.

The main finding is that each treatment has a particular pattern of side-effects and recovery which needs to be balanced against the findings from the paper reporting the clinical outcomes (Hamdy et al).

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One Size Fits All Strategy No Longer Works For Treatment of Ovarian Cancer

MedicalResearch.com Interview with:

Larissa A. Meyer, MD MPH F.A.C.O.G. Assistant Professor Dept of Gynecologic Oncology and Reproductive Medicine Houston, TX 77030-1362

Dr. Larissa Meyer

Larissa A. Meyer, MD MPH F.A.C.O.G.
Assistant Professor
Dept of Gynecologic Oncology and Reproductive Medicine
Houston, TX 77030-1362

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Despite the completion of two randomized controlled trials, controversy regarding the optimal approach for the treatment of advanced ovarian cancer remains. Our observational study highlights the importance of thoughtful selection of individuals for primary cytoreductive surgery for advanced ovarian cancer. Our results suggest that primary cytoreductive surgery may improve survival for patients with stage IIIC ovarian cancer who are likely to achieve an optimal cytoreduction, while neoadjuvant chemotherapy may be the preferred option for many women with stage IV ovarian cancer.

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Adolescent Girls Not Adequately Screened For Pregnancy Before Chemo or CT Scans

MedicalResearch.com Interview with:

Pooja Rao, MD, MSCE Assistant Professor Division of Pediatric Hematology/Oncology Milton S. Hershey Medical Center Penn State College of Medicine

Dr. Pooja Rao

Pooja Rao, MD, MSCE
Assistant Professor
Division of Pediatric Hematology/Oncology
Milton S. Hershey Medical Center
Penn State College of Medicine

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Although many chemotherapy drugs can cause birth defects, no standardized guidelines exist for pregnancy screening in adolescent female patients with cancer. Additionally, little is known about how often they are screened prior to receiving treatment.

Our study found that adolescent girls are not adequately screened for pregnancy prior to receiving chemotherapy or CT scans that could potentially harm a developing fetus. Adolescents with acute lymphoblastic leukemia, the most common childhood cancer, had the lowest pregnancy screening rates of the patients studied.

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Liquid Biopsies Hold Promise of Diagnosing Response to Chemotherapy

MedicalResearch.com Interview with:

Karen L. Reckamp, M.D. Associate Professor City of Hope Comprehensive Cancer Center Duarte, CA 91010

Dr. Karen Reckamp

Karen L. Reckamp, M.D.
Associate Professor
City of Hope Comprehensive Cancer Center
Duarte, CA 91010

MedicalResearch.com: What is the background for this study? What are the main findings?
Response:
• Approximately 60% of patients with non-small cell lung cancer (NSCLC) receiving EGFR tyrosine kinase inhibitors (TKIs) will develop TKI resistance through the acquisition of the EGFR T790M mutation.
• A major challenge for assessing EGFR mutation status in advanced NSCLC is the availability of suitable biopsy tissue for molecular testing, specifically for determination of the emergence of T790M following progression on initial EGFR TKI therapy.
• The objective of this study was to demonstrate that a highly sensitive and quantitative next-generation sequencing analysis of EGFR mutations is feasible from urine and plasma, providing comparable clinical information while potentially mitigating the issues associated with tissue biopsies.
• This blinded, retrospective study was conducted on matched tissue, urine and plasma specimens collected from 63 patients with Stage IIIB-IV NSCLC enrolled in the TIGER-X trial of rociletinib, an investigational 3rd generation tyrosine kinase inhibitor (TKI), targeting T790M.

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Scientists Develop Nanocarrier To Deliver Personalized Cocktail of Medications Directly to Tumor

MedicalResearch.com Interview with:

Adam G Alani, PhD Associate Professor of Pharmaceutical Sciences Department of Pharmaceutical Sciences College of Pharmacy Oregon State University-Oregon Health & Science University Affiliate Assistant Professor Department of Biomedical Engineering School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon

Dr. Adam Alani

Adam G Alani, PhD
Associate Professor of Pharmaceutical Sciences
Department of Pharmaceutical Sciences
College of Pharmacy
Oregon State University-Oregon Health & Science University
Affiliate Assistant Professor
Department of Biomedical Engineering
School of Medicine at Oregon Health & Science University
Oregon State University-Portland Campus at OHSU
Portland Oregon

MedicalResearch.com: What is the background for this study?

Response: Current chemotherapeutic regimens while effective are difficult for patients and affect their quality of life. Our research tackles this issue by designing a nanotherapy that can deliver multiple chemotherapeutic agents by targeting the entire tumor microenvironment and not just the cancer cells and by reducing drug resistance. This, then is intended to simplify the treatment regimen, reduce drug related side effects and extends the life of the drugs by preventing resistance should the patient need it in the future. Thus, the ultimate underlying goal is to improve the patient’s quality of life by not just maximizing the drug’s efficacy but also trying to decrease its impact on the overall lifestyle of the individual.

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Docetaxel Adds To Overall Survival in Metastatic Castration-Resistant Prostate Cancer

MedicalResearch.com Interview with:
Prof. Ronald de Wit, MD, PhD
Medical Oncologist
Medical Oncology
Erasmus MC
University Medical Center, Rotterdam

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Mainsail is one of the largest phase 3 trials in the setting of  Metastatic Castration-Resistant Prostate Cancer (mCRPC)  in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome.

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Capecitabine Cancer Treatment Can Result in Loss of Fingerprints

MedicalResearch.com Interview with:

Leni van Doorn, MSc Department of Medical Oncology Erasmus MC Cancer Institute Rotterdam, the Netherlands

Leni van Doorn

Leni van Doorn, MSc
Department of Medical Oncology
Erasmus MC Cancer Institute
Rotterdam, the Netherlands

MedicalResearch.com: What is the background for this study?

Response: The common cancer treatment capecitabine, a regular treatment for patients mostly diagnosed with breast-, colon- or gastic cancer, induces hand foot syndrome (HFS). HFS is a cutaneous condition that may lead to red palms and blisters in approximately 50% to 60% of the patients and is believed to result in the loss of fingerprints. This fingerprint loss has been described sporadically in the literature.

The main aim of our prospective study was to have a closer look of the association between  hand foot syndrome and the loss of fingerprints.

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Breast Cancer Cells Can Switch HER2 On and Off, Requiring Combination Treatment

MedicalResearch.com Interview with:

Shyamala Maheswaran, PhD Associate Professor of Surgery Harvard Medical School Assistant Molecular Biologist Center for Cancer Research

Dr. Shyamala Maheswaran

Shyamala Maheswaran, PhD
Associate Professor of Surgery
Harvard Medical School
Assistant Molecular Biologist
Center for Cancer Research

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: About 85% hormone receptor positive HER2 negative metastatic breast cancer patients show that cancer cells acquire HER2 expression during disease progression. These HER2 positive cells coexist with HER2 negative cancer cells, and these two populations are able to spontaneously oscillate between these two states; in culture and in cancers established in mice. Both HER2 positive and HER2 negative cells form tumors when injected into mice, but HER2 positive cancer cells form tumors more rapidly than HER2 negative tumors. At a molecular level, several growth factor pathways are activated in HER2 positive cancer cells, while activation of the Notch pathway, an embryonic signaling event, is observed in HER2 negative cells. Thus the HER2 positive and HER2 negative cancer cells exhibit differential sensitive to drugs: the HER2 positive cells, which are more proliferative and non-responsive to HER2-targeting agents, are responsive to chemotherapy drugs whereas the HER2 negative tumor cells are sensitive to Notch inhibitors. A combination of chemotherapeutic drugs and notch inhibitors effectively eliminate tumors formed by a mixture of these two population of cancer cells compared to either drug alone. These findings highlight the importance of tumor heterogeneity in cancer progression and drug responses and suggest that targeting all the different populations within cancers is necessary to effectively manage cancer progression.

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Pancreatic Cancer Study Finds Abraxane Superior to Paclitaxel

MedicalResearch.com Interview with:

Rajesh Kumar NV, Ph.D. Instructor of Oncology and Pathology Johns Hopkins University School of Medicine Baltimore, MD, USA Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA

Dr. Rajesh Kumar NV

Rajesh Kumar NV, Ph.D.
Instructor of Oncology and Pathology
Johns Hopkins University School of Medicine
Baltimore, MD, USA
Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA

MedicalResearch.com: What is the background for this study?

Response: Pancreatic cancer remains as one of the most deadly malignancies in the world. Recently, a cremophor-free and albumin-bound formulation of paclitaxel (nab-PTX, Abraxane) in combination with gemcitabine (GEM, Gemzar) is recently approved as a standard of care treatment option for patients with metastatic pancreatic cancer. Majority of the newly diagnosed pancreatic cancer patients use the nab-PTX plus GEM regimen. Currently there are over 100 clinical trials at various stages with this regimen as a backbone to approved medicines or investigational agents. Since widely available cremophor-based paclitaxel (PTX, Taxol) is a key chemotherapy component for the treatment of several human malignancies and the treatment cost of nab-PTX is relatively higher than PTX, patients, clinicians, third party payers and regulatory agencies have a substantial interest in understanding whether these two drugs provide a similar level of therapeutic efficacy in pancreatic cancer.

We utilized orthotopic models of human pancreatic cancer, which were shown to better recapitulate the histologic and metastatic characteristics of disease, and compared the anticancer efficacy, effect on tumor stroma modulation, metastatic spreading to distant organs and survival following GEM, PTX, nab-PTX and combinations of GEM plus PTX or nab-PTX. The preclinical trial used a total of 300 mice with established orthotopic pancreatic tumors. The tumors used for implantation were originally resected from the primary tumors of patients with moderately differentiated and poorly differentiated pancreatic cancer.

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Promising Study Evaluates Chemotherapy for Parkinson’s and Lewy Body Dementia

MedicalResearch.com Interview with:

Charbel Moussa MD. PhD Assistant Professor of Neurology Director- Laboratory for Dementia and Parkinsonism Clinical Research Director- National Parkinson's Foundation Center for Excellence Translational Neurotherapeutics Program Department of Neurology Georgetown University Medical Center Washington DC.

Dr. Charbel Moussa

Charbel Moussa MD. PhD
Assistant Professor of Neurology
Director- Laboratory for Dementia and Parkinsonism
Clinical Research Director- National Parkinson’s Foundation Center for Excellence
Translational Neurotherapeutics Program
Department of Neurology
Georgetown University Medical Center
Washington DC.

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated.

Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer’s Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau).

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Adding Plinabulin To Chemotherapy Reduces Toxicity, Improves Efficacy

MedicalResearch.com Interview with:

Dr. Lan Huang PhD Co-founder and Chief Executive Officer BeyondSpring Pharmaceuticals, Inc

Dr. Lan Huang

Dr. Lan Huang PhD
Co-founder, Chairman and CEO
BeyondSpring Pharmaceuticals, Inc

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The background for this study is the toxicity of Docetaxel chemotherapy causes inadequate dosing with Docetaxel due to dose delay, reduction or discontinuation, thus leaving the patient with inadequate chemotherapy treatment.

A main finding is a statistically significant p value of 0.002 in lower rates of grade 3 and 4 Neutropenia for patients dosed with a combination of BeyondSpring’s Plinabulin and Docetaxel compared to those patients dosed with Docetaxel alone. As a result, approximately 14 percent more patients stayed on the adequate (dense) dose of Docetaxel in the Docetaxel + Plinabulin arm as compared to Docetaxel alone.

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Cardiovascular Risks More Common With Newer TKI Chemotherapeutics for CML

MedicalResearch.com Interview with:
Torsten Dahlén MD
Centre for Hematology
Karolinska University Hospital Solna
Stockholm Sweden

MedicalResearch.com: What is the background for this study? 

Dr. Dahlén: Patients diagnosed with CML have had a dramatic increase in life-expectancy since the widespread introduction of tyrosine kinase inhibitors (TKI) in 2001. However, treatment is today regarded as life-long. We thus need to observe for late-effects of continuous TKI exposure. Recent reports have demonstrated a linkage between TKI treatment, especially more potent 2nd and 3rd generation drugs, and to the occurrence of peripheral arterial occlusive disease (PAOD). This study aimed to use real-world data utilizing Swedish population based registries together with the dedicated Swedish CML registry which contains data and follow-up on more than 98% of all CML patients diagnosed in Sweden since 2002.

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Risk Factors of Chemotherapy Induced Peripheral Neuropathy Identified

MedicalResearch.com Interview with:

Dawn L. Hershman, MD MS Professor of Medicine and Epidemiology Leader, Breast Cancer Program Herbert Irving Comprehensive Cancer Center Columbia University NY NY

Dr. Dawn Hershman

Dawn L. Hershman, MD MS
Professor of Medicine and Epidemiology
Leader, Breast Cancer Program
Herbert Irving Comprehensive Cancer Center
Columbia University
NY NY

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Hershman: Chemotherapy induced peripheral neuropathy is a common side effect of anti cancer therapy and there are currently no ways to prevent it. We used a large clinical trials database, SWOG, and linked it to Medicare claims for patients over the age of 65. We found that age and type of taxane were associated with the development of CIPN. We also found a significant increase when a taxane was given along with a platinum agent. We found a doubling of risk among patients with a prior history of diabetes. No other chronic condition was associated with an increased risk of CIPN. We found a suggestion of a decreased risk among patients with a prior history of auto-immune disease.

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ChemoBrain Linked to Decreased Dopamine Release

MedicalResearch.com Interview with:

Michael A. Johnson Ph.D Associate Professor Department of Chemistry University of Kansas

Dr. Michael Johnson

Michael A. Johnson Ph.D
Associate Professor
Department of Chemistry
University of Kansas

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Johnson: We undertook these studies because chemotherapy induced cognitive dysfunction, also known as ‘chemobrain’, has become a major health issue in recent years. For example, up to a third of patients who have undergone chemotherapy treatment for breast cancer have reported symptoms of chemobrain. These symptoms may include loss of verbal and visual memory as well as decreased mental flexibility and difficulty focusing.

For this study, we wanted to understand how treatment with chemotherapeutic agents affects the ability of neurons to communicate. An impairment of neurotransmitter release would imply that communication is hindered. This inability to communicate normally could contribute to cognitive dysfunction.
We initially measured the release of dopamine in a region of the brain called the striatum. Our measurement of dopamine in this region was motivated by two key issues: its importance in cognitive function and our ability to measure it with high temporal resolution. From a cognitive standpoint, dopamine is important because the striatum helps translate signals, received from the cortex, into plans by forwarding wanted signals to other parts of the brain and suppressing unwanted signals. Fortunately, we can easily measure dopamine release using an electrochemical technique called fast-scan cyclic voltammetry. This method allows us to not only measure how much dopamine is released from a living brain slice, but also it affords us the capability to measure how quickly dopamine is taken back up. We also measured serotonin release using this method.

Our main finding was that the ability of neurons to release dopamine was impaired after carboplatin treatment. We also found that serotonin release was similarly impaired. These release impairments corresponded to a decrease in cognitive ability of the treated rats.

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Heating Chemotherapy For Bladder Cancer Treatment May Increase Efficacy

MedicalResearch.com Interview with:

Alejandro Sousa, MD, PhD Department of Urology, Comarcal Hospital Monforte, Spain

Dr. Alejandro Sousa

Alejandro Sousa, MD, PhD
Department of Urology, Comarcal Hospital
Monforte, Spain

MedicalResearch.com: What is the background for this study?

Dr. Sousa: Bladder Cancer management has remained stable over the past 25 years, with very little in the way of new therapies or approaches being developed. Traditional treatment using intravesical Mitomycin C for Non Muscle Invasive Bladder Cancer (NMIBC) patients is limited due it’s low absorption levels. Device assisted therapies that deliver Chemo-hyperthermia offer a new hope, with the potential for improved outcomes and better disease management due the the increased drug activity and better efficacy. We wanted to investigate the optimal treatment regime for this new therapy and whether it provides a safe and effective alternative to current standard treatment. Continue reading

Fosaprepitant reduces chemoradiotherapy-induced emesis in patients treated for cervical cancer

MedicalResearch.com Interview with:
Dr Christina H Ruhlmann PhD

Department of Oncology
Odense University Hospital, Denmark 

MedicalResearch.com: What is the background for this study?

Response: The background for the GAND-emesis study is the result of a phase II study in patients with gynecological cancer receiving fractionated radiotherapy and concomitant weekly cisplatin 40 mg/m2. In that study, patients received weekly antiemetic prophylaxis with palonosetron and prednisolone, and we found that 57% of patients were continuously free from emesis (sustained no emesis) during 5 weeks of treatment. We hypothesized that the addition of a NK1 receptor antagonist could increase the number of patients with sustained no emesis, and we therefore planned the GAND-emesis study: a multinational, randomised, placebo-controlled, double-blind study that has recently been published.

MedicalResearch.com: What are the main findings?

Response: In the GAND-emesis study we compared efficacy of weekly antiemetic prophylaxis with fosaprepitant, palonosetron, and dexamethasone to placebo, palonosetron, and dexamethasone during 5 weeks of radiotherapy and concomitant weekly cisplatin 40 mg/m2 for cervical cancer. The primary endpoint was sustained no emesis during 5 weeks of treatment (competing risk analysis). We found that the proportion of patients with sustained no emesis was 48.7% for the placebo group compared with 65.7% for the fosaprepitant group, and the treatments were well tolerated. To our knowledge, this is the first study to investigate the efficacy of a NK1 receptor antagonist during 5 weeks of chemoradiotherapy.

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Patients May Benefit From New Combination Therapy For HER2-Negative Metastatic Breast Cancer

MedicalResearch.com Interview with:

Massimo Cristofanilli, MD, FACP Professor of Medicine Associate Director of Translational Research and Precision Medicine Department of Medicine-Hematology and Oncology Robert H Lurie Comprehensive Cancer Center Feinberg School of Medicine Chicago, IL 60611

Dr. Massimo Cristofanilli

Massimo Cristofanilli, MD, FACP
Professor of Medicine
Associate Director of Translational Research and Precision Medicine
Department of Medicine-Hematology and Oncology
Robert H Lurie Comprehensive Cancer Center
Feinberg School of Medicine
Chicago, IL 60611 

MedicalResearch.com: What is the background for this study? What are the main findings?

Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.  Continue reading

AML: Kinase Inhibitor Plus Standard Chemotherapy Reduces Relapse Risk

Dr. Christoph Röllig Medizinische Klinik und Poliklinik I Universitätsklinikum der Technischen Universitä Dresden, Germany

Dr. Röllig

MedicalResearch.com Interview with:
Dr. Christoph Röllig
Medizinische Klinik und Poliklinik I
Universitätsklinikum der Technischen Universitä
Dresden, Germany

Medical Research: What is the background for this study? What are the main findings?

Dr. Röllig: When this trial began in 2009, standard treatment for Acute Myelogenous Leukemia (AML) consisted of a combination of cytarabine plus anthracyclin/anthracendion and the need for improvement was obvious in the light of only around 50% long-term survivors even amongst younger patients. Although a promising approach, the use of kinase inhibitors in AML had not been shown to be beneficial and was not widely used. Sorafenib had been shown to be tolerable as single agent and in combination with commonly used chemotherapeutic agents. The results of the trial show that the addition of sorafenib to standard chemotherapy for newly diagnosed AML patients up to the age of 60 years is associated with significant prolongation of event-free survival and relapse-free survival compared to placebo plus standard chemotherapy. That means that patient who took sorafenib had less AML relapses.

To our knowledge, this is the first randomized-controlled showing that integrating a kinase inhibitor into standard intensive chemotherapy of younger patients with AML is associated with significant improvement of relapse-free survival, with no increase in treatment-related mortality. After a decade of evaluating the potential of kinase inhibitors in AML, their use in combination with standard treatment is becoming an important option for newly diagnosed younger patients.

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Hodgkin Lymphoma: Combining Targeted Drug with Immunotherapy Shows Promise

Dr. Catherine S. M. Diefenbach MD Assistant Professor of Medicine NYU Cancer Center New York, NY 10016

Dr. Diefenbach

MedicalResearch.com Interview with:
Dr. Catherine S. M. Diefenbach MD

Assistant Professor of Medicine
NYU Langone
Laura and Isaac Perlmutter Cancer Center
New York, NY 10016 

Medical Research: What is the background for this study? What are the main findings?

Dr. Diefenbach: The background of the study is that through an understanding of the unique immunobiology of Hodgkin lymphoma we can derive rational treatment strategies which may heighten the efficacy of existing therapies, and improve the outcomes for patients with relapsed disease.  In E4412 which is a national study sponsored by the Eastern Cooperative Oncology Group (ECOG-ACRIN) we explore the safety and efficacy of combination of the antibody drug conjugate brentuximab vedotin which targets CD30 on the surface of the Hodgkin lymphoma tumor cells, and immune stimulation of the T cells in the tumor microenvironment using checkpoint inhibitors.  We reported the data from the first arm of the study Brentuximab Vedotin and Ipilimumab.  To date 23 patients with relapsed Hodgkin lymphoma have been treated; the combination of brentuximab and ipilimumab was safe and well tolerated with primarily grade 1 and 2 toxicities.  In 18 patients evaluable for response the ORR was 72% with a complete response rate of 50%.

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Most Women Not Willing To Take Medications To Prevent Breast Cancer

Sam Smith, PhD CPsychol Cancer Research UK Postdoctoral Fellow Centre for Cancer Prevention Queen Mary University of London Wolfson Institute of Preventive Medicine London

Sam Smith, PhD CPsychol

MedicalResearch.com Interview with:
Sam Smith, PhD CPsychol

Cancer Research UK Postdoctoral Fellow
Centre for Cancer Prevention
Queen Mary University of London
Wolfson Institute of Preventive Medicine
London

Medical Research: What is the background for this study? What are the main findings?

Dr. Smith:  Several trials have demonstrated that agents (e.g. tamoxifen) can be used to prevent breast cancer among women at increased risk. However, their effectiveness is dependent upon their appropriate use by this patient group. Several studies have suggested that uptake is low, and that women are not taking the medications for the full 5 year course. We attempted to synthesize the evidence investigating these topics, as well as identify the factors affecting these behaviours.

The main findings are that only 1 in 6 women (16.3%) were willing to start taking oral medications to prevent breast cancer.

Furthermore, uptake rates were lower in routine clinical practice (9%) compared with trial enrollment rates (25%), suggesting that there may be problems with implementing chemoprevention within routine clinical care. We noted that day to day adherence and persistence over a short period (e.g. 1 year) was adequate, but when looking at the longer term studies only 1 in 10 reported that >80% of women were still taking their medications at the 5 year end point. Women may not be experiencing the full preventive effect of these medications.

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Chemotherapy-induced Peripheral Neuropathy Linked To Cognitive Dysfunction In Breast Cancer Patients

MedicalResearch.com Interview with:
Kelly N. H. Nudelman, Ph.D.
Department of Radiology and Imaging Sciences
Indiana University-Purdue University Indianapolis (IUPUI)
Indianapolis, IN 46202

Medical Research: What is the background for this study?

Dr. Nudelman: Varying levels of cognitive problems and related changes in brain structure and function have been reported in breast cancer patients treated with chemotherapy. Pain has also been associated with altered brain structure and function. However, the association of chemotherapy-induced peripheral neuropathy (CIPN), a side-effect of chemotherapy treatment characterized by nerve damage primarily in the extremities, has not been specifically investigated for association with cognitive symptoms in breast cancer. We used data from a prospective, longitudinal breast cancer cohort to investigate the relationship of CIPN and neuroimaging measures of cognitive dysfunction. 

Medical Research: What are the main findings?

Dr. Nudelman: We found that increased chemotherapy-induced peripheral neuropathy symptoms were associated with resting brain blood flow increase in regions known to be involved in pain processing. We also found that decreased frontal lobe gray matter density was correlated with these changes, suggesting a link between chemotherapy-induced peripheral neuropathy and cognitive dysfunction.

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Gene Score Identified Breast Cancer Patients Who Don’t Benefit From Chemotherapy

Dr. Kathy D. Miller, MD Indiana University Melvin and Bren Simon Cancer CenterMedicalResearch.com Interview with:
Dr. Kathy D. Miller, MD
Indiana University Melvin and Bren Simon Cancer Center

Medical Research: What is the background for this study? What are the main findings?

Dr. Miller: Previous studies had found a small but real benefit with the addition of chemotherapy to anti-estrogen treatment in patients with hormone sensitive disease. The challenge for patients and clinicians has always been that the benefit of chemotherapy is quite small and the toxicity can be substantial. The Oncotype Dx recurrence score assay was developed to identify patients who could safely be treated with anti-estrogen therapy alone (and conversely those who truly need and would derive a much larger benefit from chemotherapy). When the Oncotype Dx RS was applied to samples stored from a previous randomized trial, patients with low risk scores didn’t seem to benefit from chemotherapy. While those initial results had some impact on treatment, many were concerned about eliminating chemotherapy on the basis of one small retrospective trial.

The overall trial enrolled 10,253 women. 1626 (15.9%) had a Recurrence Score of 0-10 and were assigned to receive antiestrogen therapy alone without chemotherapy. After five years 99.3% (98.7, 99.6%) for were free of distant relapse (that is to say, 99.3% of women had NOT had recurrence of breast cancer at distant sites in the body). Overall survival was 98%.

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Many Patients Require Hospitalization During Chemotherapy

Dr. Rebecca Prince Clinical Research Fellow and first author

Dr. Rebecca Prince

MedicalResearch.com Interview with:
Dr. Rebecca Prince MBBS
Clinical Research Fellow and first author and

Monika K. Krzyzanowska, MD MPH FRCPC Medical Oncologist, Princess Margaret Cancer Centre Associate Professor, Dept of Medicine and Institute of Health Policy, Management & Evaluation, University of Toronto Senior Adjunct Scientist, Institute for Clinical Evaluative Sciences Clinical Lead, Quality Care & Access, Systemic Treatment Program,

Dr Monika Krzyzanowska

Monika K. Krzyzanowska, MD MPH FRCPC
Medical Oncologist, Princess Margaret Cancer Centre, Associate Professor, Dept of Medicine and Institute of Health Policy, Management & Evaluation, University of Toronto
Senior Adjunct Scientist, Institute for Clinical Evaluative Sciences
Clinical Lead, Quality Care & Access, Systemic Treatment Program, Cancer Care Ontario Toronto, ON 

Medical Research: What is the background for this study? What are the main findings?

Response: This study was inspired by our previous work using administrative data in which we found that a large proportion of patients receiving chemotherapy in routine practice were visiting the emergency department and being admitted to hospital. Our perception was that the frequency of these events was higher than expected but when we went to look what was expected, ie. how often were people ending up in hospital during treatment in clinic trials, this data was not readily available. This led us to perform a systematic review of the literature including a comparison of hospitalization rates between patients treated in clinical trials and patients in similar clinical scenarios treated in routine practice. We ended up focusing on metastatic lung cancer as that was one of the clinical scenarios where we were able to identify published data from both clinical trials and routine practice.

The main finding of our study is that hospitalizations are very common during chemotherapy. We compared patients with metastatic lung cancer being treated in routine practice and clinical trials and found that that approximately half (51%) of patients treated in routine practice were hospitalized during chemotherapy, compared to 16% of trial patients. We also found that very few clinical trials reported this information which is routinely collected during the trial.

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Protein Keratin Promotes Cancer Growth and Chemotherapy Resistance

Kenneth R. Shroyer, MD, PhD The Marvin Kuschner Professor and Chair Department of Pathology Stony Brook Medicine Stony Brook, NY

MedicalResearch.com Interview with:
Kenneth R. Shroyer, MD, PhD
The Marvin Kuschner Professor and Chair
Department of Pathology
Stony Brook Medicine
Stony Brook, NY

 

 

Medical Research: What is the background for this study? What are the main findings?

Dr. Shroyer: Patients that appear to have the same type of cancer often respond very differently to treatment; while some patients appear to go into long-term regression or are cured, others follow a rapid downhill course and ultimately die of their disease. This suggests that there are fundamental differences between tumors at the biologic level that are not detected by current clinical measures.

In this study, we report the unexpected finding that cancer patients that have high levels of a protein called Keratin 17 (K17) have decreased long-term survival when compared to patients that express little to no K17 in their tumors. In addition, we found that K17 enters the nucleus of tumor cells to mediate the degradation of the master regulator of cell division and tumor growth key tumor suppressor protein, p27. Furthermore, we identified that K17 increases the resistance of tumor cells to chemotherapy.

These are critical findings because this is the first report that a keratin is an oncoprotein that can enter the nucleus to promote the development of cancer and resistance to chemotherapy.

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Distance, Insurance and Number of Oncologists Limit Access To Chemotherapy

Anna Lin, MBA, PHD Senior Epidemiologist, Health Services Research American Cancer Society, Inc. 250 Williams St. Atlanta, GA 30303MedicalResearch.com Interview with:
Anna Lin, MBA, PHD
Senior Epidemiologist, Health Services Research
American Cancer Society, Inc.
250 Williams St.
Atlanta, GA 30303

Medical Research: What is the background for this study?

Dr. Lin: Evidence-based guidelines recommend the use of adjuvant chemotherapy in patients with Stage III colon cancer within 90 days of colectomy to improve disease-free and overall survival; however, a substantial proportion of patients do not receive this treatment.  Geographic access to care may be associated with receipt of chemotherapy but has not been fully examined.

Medical Research: What are the main findings?

Dr. Lin: The main findings of this study indicate that patients traveling more than 50 miles were less likely to receive adjuvant chemotherapy for Stage III node-positive colon cancer.  In addition, patients who had either no insurance or public (non-private) insurance and resided in areas with low density of oncologists were less likely to receive adjuvant chemotherapy.

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Next Generation Drug Rolapitant Helps Prevent Chemotherapy-induced Nausea and Vomiting

Bernardo L. Rapoport M. D. The Medical Oncology Centre of Rosebank Johannesburg, South AfricaMedicalResearch.com Interview with:
Bernardo L. Rapoport M. D.
The Medical Oncology Centre of Rosebank
Johannesburg, South Africa

Medical Research: What is the background for this study? What are the main findings?

Dr. Rapoport: Chemotherapy-induced nausea and vomiting (CINV) is one of the most feared side effects of chemotherapy, and can lead to dose reductions or discontinuations of life-extending anti-cancer therapy. In the past, the serotonin (5-HT3) receptor antagonists, such as granisetron, palonosetron , and ondansetron, have shown effectiveness in preventing acute CINV (0-24 hours after chemotherapy administration), but many chemotherapies, such as cisplatin, carboplatin, and anthracycline/cyclophosphamide combinations, can cause delayed chemotherapy-induced nausea and vomiting that occurs from >24 hours to 5 days or more after chemotherapy. Neurokinin-1 receptor antagonists (NK-1 RAs) work though the substance P signaling pathway and are effective at preventing the delayed phase of chemotherapy-induced nausea and vomiting. Aprepitant was the first NK-1 RA to come to market in 2003, followed by a fixed dose of netupitant plus palonosetron late last year.

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Chemotherapy At End Of Life May Bring More Harm Than Good

Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Director, Center for Research on End of Life Care Weill Cornell Medical College New York Presbyterian Hospital New York City, New York MedicalResearch.com Interview with:
Holly G. Prigerson, Ph.D.

Irving Sherwood Wright Professor in Geriatrics
Professor of Sociology in Medicine
Director, Center for Research on End of Life Care
Weill Cornell Medical College
New York Presbyterian Hospital
New York City, New York

Medical Research: What is the background for this study? What are the main findings?

Dr. Prigerson: End-stage cancer patients are often offered “palliative chemotherapy” so we wanted to know if it, indeed, palliated their symptoms. ASCO guidelines recommend chemotherapy only be given to those with good performance status
(e.g. ecog scores < 3).

We found over half of these cancer patients (who died a median of 3.8 months from our baseline assessment), were receiving chemotherapy at our baseline assessment and that it did not improve quality of life in the last week of life for patients with poor baseline performance status and it significantly harmed quality of life in the patient’s final week for those with good performance status.

Medical Research: What should clinicians and patients take away from your report?

Dr. Prigerson: For terminally ill cancer patients, regardless of performance status, more harm than benefit to quality of life appears to result from use of chemotherapy. There is a need for open, honest discussion of the pros and cons of chemo for this group of patients.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Prigerson: We need to examine the factors influencing receipt of palliative chemotherapy and the mechanisms through which it results in worse quality of death. We also need to examine cost effectiveness of such care.

Citation:

Prigerson HG, Bao Y, Shah MA, et al. Chemotherapy Use, Performance Status, and Quality of Life at the End of Life. JAMA Oncol. Published online July 23, 2015. doi:10.1001/jamaoncol.2015.2378.

 

Holly G. Prigerson, Ph.D. (2015). Chemotherapy At End Of Life May Bring More Harm Than Good 

Pairing Doxorubicin with Natural Products May Offer Some Cardiac Protection

Adam G Alani, PhD Assistant Professor of Pharmaceutics Department of Pharmaceutical Sciences College of Pharmacy Oregon State University-Oregon Health & Science University Affiliate Assistant Professor Department of Biomedical Engineering School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon 97201-5042 MedicalResearch.com Interview with:
Adam G Alani, PhD
Assistant Professor of Pharmaceutics
Department of Pharmaceutical Sciences
College of Pharmacy
University Affiliate Assistant Professor
Department of Biomedical Engineering
School of Medicine at Oregon Health & Science University Oregon State University-Portland Campus at OHSU Portland Oregon

Medical Research: What is the background for this study? What are the main findings?

Dr. Alani: Doxorubicin, a potent anticancer agent is being under-utilized in the clinic due to its life threatening cardiotoxicity.  This cardiotoxicity has imposed a life dose limit of 450 -550 mg/m2 which restricts clinicians use of this drug for subsequent relapses when a patient has responded to the drug favorably in the past.  In our lab, we are looking to pair this drug with natural products that have shown both cardioprotective effects and while enhancing the potency of common chemotherapeutics like doxorubicin.  Using this complementary approach with a high dose of doxorubicin known to cause cardiotoxicity, we have fully/ partially mitigated this cardiotoxicity in healthy mice. The goal is not to change the dosing regimen for doxorubicin, but to pair it with our nanoscale drug delivery systems containing these natural products as complementary therapy.

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3-Drug Combination May Better Reduce Nausea-Vomiting During Chemotherapy

MedicalResearch.com Interview with:
Junichi Nishimura MD, PhD
Assistant professor
Osaka University in Japan

Medical Research: What is the background for this study? What are the main findings?

Dr. Nishimura: Oxaliplatin is classified as moderately emetogenic chemotherapy and 2-drug combination antiemetic therapy is recommended for Oxaliplatin based chemotherapy including FOLFOX and XELOX in all guidelines for antiemesis. Nausea and vomiting are still frequent adverse events which decrease the patient’s QOL. However, there was no study investigating whether 3-drug combination antiemetic therapy (5HT3 receptor antagonist+dexamethasone+aprepitant) reduce chemotherapy-induced nausea and vomiting. In this study, we conducted a multicentre, randomized phase III study to evaluate the usefulness of the combined use of aprepitant in colorectal cancer patients treated with Oxaliplatin based chemotherapy. In this phase III study, 3-drug combination therapy significantly increased the inhibition rate of vomiting which was the primary endpoint of this study. Moreover, the inhibition rate of nausea, complete response (no vomiting and no rescue medication use), and complete protection (no vomiting , no rescue medication use and no moderate or worsened nausea) was significantly higher in aprepitant group in overall and delayed phase. We, next, compared the inhibition of vomiting and nausea between males and females in delayed phase. When patients were grouped by sex regardless of the assigned treatment group, females were more affected by nausea and vomiting than males. Finally, in female, aprepitant did significantly prevent nausea and vomiting as well as increased chance of complete protection.

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New Therapeutic Target May Make Chemotherapy More Effective Against Pancreatic Cancer

Dr. Janaiah Kota Assistant Professor, Department of Medical and Molecular Genetics Indiana University School of Medicine Indianapolis, IN,MedicalResearch.com Interview with:
Dr. Janaiah Kota
Assistant Professor, Department of Medical and Molecular Genetics
Indiana University School of Medicine
Indianapolis, IN,


Medical Research: What is the background for this study?

Dr. Kota: Pancreatic cancer tumors are surrounded by a thick fibrotic shell known as “stroma” which protects the cancer cells from anticancer drugs such as chemotherapy. However, complete depletion of tumor stroma leads to more aggressive disease and decreases survival. The stromal abundance needs to be appropriately moderated (i.e. not too much nor too little) in pancreatic tumors. None of the current anti-stromal therapies have been effective enough to resolve this problem. Unless we understand the molecular signatures associated with tumor stroma, it will be challenging to develop an effective therapeutic strategy.

There is a desperate need to develop new therapies for pancreatic cancer as only 7 percent of people with the disease survive more than 5 years after diagnosis. According to the National Cancer Institute, there will be an estimated 48,960 new cases of pancreatic cancer and 40,560 deaths from the disease in 2015.

Medical Research: What are the main findings?

Dr. Kota: We found that the loss of microRNA-29 (miR-29) is a common phenomenon of pancreatic cancer stromal cells, and that by restoring it, the viability and growth of the cancerous cells and stromal accumulation was reduced. The use of miR-29 as a therapeutic agent may be more effective in targeting reactive stroma, as a single miRNA regulates the expression of several genes associated with disease mechanisms. We expect that this novel approach has the potential to overcome the problems associated with current anti-stromal drugs and could lead to improved therapeutic strategies, enhanced drug delivery to the tumor bed, and, in the future, improved patient survival.
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Blood Based Biomarker May Guide Therapy For Advanced Prostate Cancer

Emmanuel S. Antonarakis, M.B.B.CH   Department of Urology and Oncology Johns Hopkins University School of Medicine Baltimore, MarylandMedicalResearch.com Interview with:
Emmanuel S. Antonarakis, M.B.B.CH
Department of Urology and Oncology
Johns Hopkins University School of Medicine
Baltimore, Maryland

Medical Research: What is the background for this study? What are the main findings?

Dr. Antonarakis: In a previous publication, we reported that detection of the androgen receptor splice variant 7 (AR-V7; an abnormal version of the androgen receptor) in circulating tumor cells from patients with advanced prostate cancer was associated with resistance to hormonal therapies such as abiraterone and enzalutamide. Here, we aimed to explore the role of AR-V7 in the context of chemotherapy treatment. We showed that detection of AR-V7 was not associated with resistance to the chemotherapy drugs docetaxel or cabazitaxel, and that AR-V7-positive patients could still derive benefit from these chemotherapies. Continue reading

HRD Score Can Help Predict Response To Some Chemotherapeutic Agents

MedicalResearch.com Interview with:
Dr. Kirsten Timms, PhD
Program Director
VP Biomarker Discovery at Myriad Genetics Inc

Medical Research: What is the background for this study? What are the main findings?

Dr. Timms: The Homologous Recombination Deficiency (HRD) score is a tumor biomarker which quantitates genomic rearrangements associated with defects in DNA damage repair. It has been shown in multiple studies that HRD score can identify tumors sensitive to DNA damaging agents such as platinum salts or PARP inhibitors. Many tumors are spatially heterogeneous: different parts of a tumor show variation at both the genomic level, and in their appearance. This tumor heterogeneity has the potential to negatively impact the accuracy of biomarker tests. This study assessed the consistency of the HRD score in multiple biopsies obtained from the same cancer to understand the impact of tumor heterogeneity on the HRD score. The main finding of this study is that the HRD score is highly conserved between different biopsies of the same tumor.

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Individualized Sunitinib Dosing Improved Response Rate in Renal Cell Cancer

MedicalResearch.com Interview with:
Georg A. Bjarnason, MD, FRCP(C)
The Anna-Liisa Farquharson Chair in Renal Cell Cancer Research
Associate Professor, Faculty of Medicine, University of Toronto
Division of Medical Oncology, Sunnybrook Odette Cancer Centre
Toronto, ONT, Canada

Medical Research: What is the background for this study?

Dr. Bjarnason: Higher sunitinib drug exposure is associated with better response (RR), progression free (PFS) and overall survival (OS). Retrospective data show poorer PFS and OS in patients with minimum toxicity on the 28 day (d)/14 d schedule vs patients needing dose/schedule changes. We hypothesized that toxicity-driven dose/schedule changes would optimize drug exposure.

Medical Research: What are the main findings?

Dr. Bjarnason: The main findings of this report include:

  1. Individualized Sunitinib therapy is safe and feasible in a multicenter setting (13 study canters).
  2. Response rates (CR+PR+ SD rate of 89.2%) are among the best for any tyrosine-kinase inhibitor (TKI) in renal cell cancer with implications for dosing of sunitinib in other indications and for the dosing of other TKI’s. Only 10% of patients were refractory to Sunitinib. This has been around 20% in other studies.3. Dose intensity was improved in 65% of patients vs. the standard dosing schema for Sunitinib. 20% of patients were dose escalated, and much fewer patients needed dose reductions or stopped due to toxicity.
  3. The primary endpoint is PFS and the data are too early for this but: 37/102 (36.3%) patients have been on therapy longer than the 8.5 Mo PFS in the EFFECT comparator trial and 25/83 (30.1%) of these patients are still on therapy.  For 49 patients with CR+PR the median time on therapy is 14.3 months (29 patients (59%) still on treatment). For 42 patients with standard treatment the median time in therapy is 6.8 months (15 patients (34%) still on treatment).

Medical Research: What should clinicians and patients take away from your report?

Dr. Bjarnason: Many oncologists are already using alternate schedules for sunitinib because of the toxicity associated with the standard 4/2 schedule. These data provide them with an algorithm for individualized sunitinib therapy that is safe and associated with a very good response rate and time on therapy.

Medical Research: What recommendations do you have for future research as a result of this study?

Dr. Bjarnason: The safety and activity of other targeted drugs might be optimized by individualizing therapy based on toxicity.

Citation:

Presented at 2015 ASCO Meeting:

Phase II study of individualized sunitinib as first-line therapy for metastatic renal cell cancer

J Clin Oncol 33, 2015 (suppl; abstr 4555)

Author(s):

Georg A. Bjarnason, Jennifer J. Knox, Christian K. Kollmannsberger, Denis Soulieres, D. Scott Ernst, Christina M. Canil, Eric Winquist, Pawel Zalewski, Sebastien J. Hotte, Scott A. North, Daniel Yick Chin Heng, Robyn Jane Macfarlane, Peter M. Venner, Ian Tannock, Anil Kapoor, Bernhard J. Eigl, Aaron Richard Hansen, Piotr Czaykowski, Ben Boyd, Naveen S. Basappa; Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, ON, Canada; Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, ON, Canada; BC Cancer Agency, Vancouver Cancer Centre, Vancouver, BC, Canada; Centre Hospitalier de l’Université de Montréal, Montreal, QC, Canada; London Regional Cancer Centre, London, ON, Canada; Ottawa Reg Cancer Centre, Manotick, ON, Canada; London Health Sciences Centre, London, ON, Canada; Lakeridge Health, Oshawa, ON, Canada; Juravinski Cancer Centre, Hamilton, ON, Canada; Cross Cancer Institute, Edmonton, AB, Canada; Tom Baker Cancer Center, University of Calgary, Calgary, AB, Canada; Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada; Cross Cancer Inst, Edmonton, AB, Canada; Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada; BC Cancer Agency, Vancouver, BC, Canada; Princess Margaret Hospital, Toronto, ON, Canada; CancerCare Manitoba, Winnipeg, MB, Canada; Ozmosis Research Inc, Toronto, ON, Canada

 

MedicalResearch.com Interview with: Georg A. Bjarnason, MD, FRCP(C) (2015). Individualized Sunitinib Dosing Improved Response Rate in Renal Cell Cancer 

Myriad Presents Data on Expanded Cancer Genetics and Chemotherapy Susceptibility Testing

MedicalResearch.com spoke with Dr. Jonathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago.  Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.MedicalResearch.com spoke with
Dr. Johnathan Lancaster, MD, Ph.D. at the 2015 ASCO meeting in Chicago.
Dr. Lancaster is the new Vice President of Medical Affairs for Oncology, Myriad Genetic Laboratories, at Myriad. Dr. Lancaster jointed Myriad in February 2015 after twelve years at the Moffitt Cancer Center. Prior to Moffitt, Dr. Lancaster was medical director of the Gynecologic Dysplasia Clinic at Duke University Medical Center in Durham, NC, where he also completed his residency and fellowship training.

MedicalResearch.com: Can you tell us a little more about your background? How did you come to work at Myriad?

Dr. Lancaster: My background and interests lie at the intersection of patient care and the molecular and genetic understanding of cancer. I completed my MD and Ph.D. in molecular genetics at the University of Wales, and then came to Duke for a research fellowship and residency training in Obstetrics & Gynecology. I spent twelve years as a gynecology-oncology surgeon.

At the Moffitt Cancer Center, I ran a research lab attempting to understand the molecular and genetic underpinnings of ovarian cancer development and progression. Our translation research attempted to identify markers, or microRNAs, that help predict ovarian tumors’ response to chemotherapeutic agents.

I also have experience in the management and financial issues facing medicine and health care. While at Moffitt, I was president of the 350-member Moffitt Medical Group, deputy physician-in-chief and director of the Center for Women’s Oncology.

The opportunity at Myriad Genetics allows me to utilize my experience in all three interests, clinical care, research and management, to contribute to a broader mission of cancer treatment and prevention.

MedicalResearch.com: What studies are being presented at ASCO this year by Myriad associated researchers?

Dr. Lancaster: There are 19 abstracts presented by Myriad at ASCO 2015, which is a testament to the emphasis Myriad places on basic and translational research (Myriad reinvests $300-400 of the proceeds from every clinical test performed into research). The studies center around two main themes:

1: An enhanced panel of genes, called MyRisk, to test for increased risk of hereditary cancers.

2: The use of Homologous Recombination Deficiency (HRD) testing and score, called MyChoice, which helps clinicians determine which patients may respond best to some chemotherapeutic agents.

MedicalResearch.com: What does the MyRisk panel offer over and above the information learned from BRAC1/2 testing? Why should a patient or clinician want this testing performed?

Dr. Lancaster: The MyRisk panel tests for 25 state-of-the-art genes with the goal of determining who may be at increased risk for certain malignancies even if they are BRAC1/2 negative. The typical patient is one who has a family history of cancer but may have been told she doesn’t have the ‘breast cancer gene’ because she is BRAC1/2 negative. We now know that up to 50% of these patients may carry other genes that make them more susceptible to cancer. Panel testing allows clinicians to identify many more patients at risk for cancer who would have been missed with more traditional BRAC1/2 testing alone.

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Genomic Instability Biomarker May Help Predict Treatment Response In Triple Negative Breast Cancer

MedicalResearch.com Interview with:
Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CA
Melinda L. Telli, M.D.
Assistant Professor of Medicine
Stanford University
Division of Medical Oncology

Stanford, CA 94305-5826

Medical Research: What is the background for this study? What are the main findings?

Response: A major goal of this study was to explore a DNA damaging chemotherapy regimen in patients with newly diagnosed early-stage triple-negative or BRCA1/2 mutation-associated breast cancer. This was based on the hypothesis that these types of tumors are more responsive to DNA damaging therapeutics. A second major goal was to identify predictors of response to this platinum-based therapy among patients with sporadic triple-negative breast cancer (TNBC).

Overall, this study demonstrated that the non-anthracycline and non-taxane neoadjuvant regimen of gemcitabine, carboplatin and iniparib resulted in a 36% pathologic complete response rate (pCR). This compares favorably to pCR rates commonly observed with anthracycline and taxane-based regimens in this group of patients. The response rate was higher among triple-negative breast cancer patients with a germline BRCA1 or BRCA2 mutation (56%).

Given the hypothesis of underlying DNA repair defects in sporadic triple-negative breast cancer, we also evaluated a novel measure of genomic instability to detect the accumulation of changes in the genomic landscape of a tumor attributable to defective homologous recombination DNA repair. Homologous recombination deficiency was assessed by loss of heterozygosity (HRD-LOH) in pretreatment core breast biopsies. Very importantly, we found that the HRD-LOH assay was able to identify patients with sporadic TNBC lacking a BRCA1 or BRCA2 mutation, but with an elevated HRD-LOH score, who achieved a favorable pathologic response. Continue reading

Signal Pathway Allows Lung Cancer Cells To Resist Chemotherapy

Trevor G. Bivona MD PhD Assistant Professor, Hematology and Oncology UCSFMedicalResearch.com Interview with:
Trever G. Bivona MD PhD
Assistant Professor, Hematology and Oncology
UCSF

Medical Research: What is the background for this study? What are the main findings?

Dr. Bivona: Resistance to targeted cancer therapy remains a problem in the treatment of cancer patients.  These targeted drugs are often effective at shrinking the tumor, but do so incompletely.  This incomplete response results in residual disease that is drug resistant and eventually grows to cause relapse that is lethal in patients.  We investigated the mechanisms underlying this residual disease state in lung cancers treated with the EGFR targeted therapy Tarceva.  We discovered that the tumor cells survival initial EGFR targeted therapy treatment by activating a signaling pathway called NF-kappa B.  This NF-kappa B pathway then promotes tumor cell survival, residual disease, and eventual relapse in the lung cancer models we studied.

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