Small Cell Lung Cancers Form Chemotherapy-Resistant Circulating Tumor Spheres

MedicalResearch.com Interview with:

Prof. Gerhard Hamilton Department of Obstetrics and Gynecology Medical University of Vienna 

Prof. Hamilton

Prof. Gerhard Hamilton
Department of Obstetrics and Gynecology
Medical University of Vienna

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

Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the
low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness.

Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs – if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.

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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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Precision Therapy In Early Stages For Triple Negative Breast Cancer

MedicalResearch.com Interview with:
Eran Andrechek, PhD

Eran Andrechek, PhD Associate Professor Department of Physiology Michigan State University East Lansing, MI

Associate Professor
Department of Physiology
Michigan State University
East Lansing, MI 

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

Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment.  Other types can be treated with personalized medicine, resulting in better outcome.  For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself.  The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy.

The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options.  Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer.  Continue reading

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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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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Image-Guided Biopsies May Reduce Need For Surgery in Breast Cancer Patients Who Respond to Chemotherapy

MedicalResearch.com Interview with:

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

Dr. Henry M. Kuerer

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

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

Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation.

We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed?

The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not.

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Breast Cancer: 21-gene assay Can Help Choose Neoadjuvant Therapy

MedicalResearch.com Interview with:

Harry D. Bear, MD, PhD Walter Lawrence, Jr. Distinguished Professor of Oncology; Chair, Division of Surgical Oncology, Department of Surgery; Professor, Departments of Surgery, Microbiology & Immunology, VCU School of Medicine; Director, Breast Health Center, VCU Massey Cancer Center; Medical Director Massey Cancer Center Clinical Trials Office Virginia Commonwealth University

Dr. Harry Bear

Harry D. Bear, MD, PhD
Walter Lawrence, Jr. Distinguished Professor of Oncology;
Chair, Division of Surgical Oncology, Department of Surgery;
Professor, Departments of Surgery, Microbiology & Immunology,
VCU School of Medicine; Director, Breast Health Center,
VCU Massey Cancer Center; Medical Director
Massey Cancer Center Clinical Trials Office
Virginia Commonwealth University

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

Response: This was based on the utility of using the 21-gene assay of breast cancers to guide the decision to add chemotherapy to the adjuvant therapy for patients with hormone-responsive breast cancer.

We hypothesized that the Recurrence Score could be used to guide the choice of neoadjuvant therapy for women with hormone responsive breast cancer who needed pre-operative treatment to shrink the tumor and make breast conservation feasible.

The main findings were:
1) Using the 21-gene RS assay to guide  neoadjuvant therapy is feasible.
2) Clinical and pathologic responses were not negatively impacted by using neoadjuvant hormonal therapy in patients with RS<25.
3) Patients whose tumors have a low recurrence score can be safely and effectively treated with hormone therapy alone.

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

Response: These results support the use of the recurrence score to choose hormonal vs. chemotherapy, enabling more personalized care and optimizing outcomes for patients with ER+ early breast cancerwho are candidates for NST.

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

Response: I would like to see a larger prospective trial to build on the evidence from this pilot study that would provide definitive evidence for the use of genomic profiling of breast cancers to guide neoadjuvant therapy.

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

Disclosure:  Study supported by Genomic Health Inc.

Citation:
39th Annual SABCS 2016
Abstract: P2-10-04
Poster: “Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial”
Authors: Bear HD, Wan W, Robidoux A, Rubin P, Limentani S, White, Jr. RL, Granfortuna J, Hopkins JO, Oldham D, Rodriguez A, Sing AP.
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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MARIANNE Study of HER2+ Metastatic Breast Cancer: Trastuzumab Emtansine With or Without Pertuzumab vs Trastuzumab Plus Taxane

MedicalResearch.com Interview with:

Edith Perez, MD Vice President and Head of U.S. Medical Affairs Genentech BioOncology

Dr. Edith Perez

Edith Perez, MD
Vice President and Head of U.S. Medical Affairs
Genentech BioOncology

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

Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy.

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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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Abraxane Demonstrates Benefit Over Paclitaxel in Metastatic Breast Cancer

MedicalResearch.com Interview with:

Corey Pelletier PhD Director, Health Economics & Outcomes Research at Celgene Celgene Corporation Summit, NJ

Dr. Corey Pelletier

Corey Pelletier PhD
Director, Health Economics & Outcomes Research
Celgene Corporation
Summit, NJ

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

Response: In a phase III clinical trial, ABRAXANE demonstrated significant improvement in ORR vs paclitaxel in patients with metastatic breast cancer. Celgene initiated this study because limited data exist on the comparative effectiveness of ABRAXANE vs paclitaxel for patients with metastatic breast cancer, including HR+/HER2- and triple negative (TN) metastatic breast cancer (MBC), in a real-world setting. This study used a U.S. based electronic medical record (EMR) dataset to evaluate the real-world comparative effectiveness of second-line ABRAXANE vs paclitaxel in patients with MBC and included patients with HR+/HER2- or TN MBC. This study also assessed adverse events and use of supportive care in this patient population.

The median time to treatment discontinuation (TTD) for ABRAXANE vs paclitaxel was 4.50 vs 2.83 months (adjusted P<0.0001*) in all patients. Patients with HR+/HER2- or TN MBC had similar TTD. The median time to next treatment (TTNT) in all patients was 5.9 vs 4.2 months (adjusted P=0.2140*) for ABRAXANE vs paclitaxel, respectively. Patients receiving ABRAXANE had less fatigue, neuropathy, and anemia compared to patients receiving paclitaxel. Patients treated with ABRAXANE also used less antiemetics, and had fewer treatments for hydration or allergic reaction compared to those treated with paclitaxel. Patients treated with paclitaxel used less GCSF and had fewer treatments for bone loss compared to those treated with ABRAXANE.

*TTD and TTNT were adjusted for age, number of metastases, targeted agent use, adjunctive chemotherapy, HER2 status, TN status, and CCI score without age.

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Lung Cancer: Adjusting Afatinib Dose Reduced Side Effects With No Impact on Efficacy

MedicalResearch.com Interview with:

Chih-Hsin Yang MD PhD Department of Oncology National Taiwan University Hospital

Dr. Chih-Hsin Yang

Chih-Hsin Yang MD PhD
Department of Oncology
National Taiwan University Hospital

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

Response: LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, Phase III trials of afatinib versus chemotherapy (pemetrexed / cisplatin and gemcitabine / cisplatin, respectively) as first-line treatment for patients with EGFR mutation-positive, advanced and metastatic non-small-cell lung cancer (NSCLC). Both trials met their primary endpoint of PFS with afatinib significantly delaying tumor growth when compared to standard chemotherapy.

A post-hoc analysis of the studies was conducted to look at the incidence and severity of common adverse events (AEs) before and after afatinib dose reduction and the PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not.

The results showed dose reductions were associated with decreases in the incidence and severity of treatment-related AEs, while median progression-free survival (PFS) was similar in patients who dose-reduced within the first six months of treatment versus those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).

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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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70-Gene Signature Can Help Identify Early-Stage Breast Cancer Patients Who Do Not Need Chemotherapy

MedicalResearch.com Interview with:

Prof. Laura van ’t Veer, PhD Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center Angela and Shu Kai Chan Endowed Chair in Cancer Research UCSF Helen Diller Family Comprehensive Cancer Center

Dr. Laura Van’t Leer

Prof. Laura van ’t Veer, PhD
Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center
Angela and Shu Kai Chan Endowed Chair in Cancer Research
UCSF Helen Diller Family Comprehensive Cancer Center

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

Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment.

MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit.

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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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Sticky Hydrogel Can Deliver Triple Therapy Directly To A Tumor

MedicalResearch.com Interview with:

Natalie Artzi PhD Assistant Professor at Brigham and Women’s Hospital, Harvard Medical School Associate member of the Broad Institute of Harvard and MIT.

Dr. Natalie Artzi

Natalie Artzi PhD
Assistant Professor at Brigham and Women’s Hospital, Harvard Medical School
Associate member of the Broad Institute of Harvard and MIT.

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

Response: We have shown in the last years that dendrimer:dextran adhesive hydrogels represent a platform with ahuge potential for delivery. In 2015, we were able to report that these gels doped with smart nanoparticles could sense and differentially react with the disease microenvironment (e.g. can sense the tissue microenvironment by detecting the expression of specific genes related with multidrug resistance, Conde et al. PNAS 2015), potentiating targeted drug release and uptake in certain disease settings.

Later, these hydrogels prove to be incredibly useful for miRNA delivery by using the self-assembly of a triple-helix forming miRNA structure that lead to nearly 90% levels of tumor shrinkage two weeks post-gel implantation (Conde et al. Nature Materials 2016a).

Here, we took a step-forward, and used these hydrogels to develop a prophylactic patch for gene, chemo and phototherapy in a triple-combination approach to achieve complete tumor resection when applied to non-resected tumors and to the absence of tumor recurrence when applied following tumor resection (Conde et al. Nature Materials 2016b). This study also identifies the molecular and genetic pathways triggered in response to the three therapeutic modalities − photo-, gene- and chemo-therapy − by tumor gene expression profiling in treated mice.

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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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Immunotherapy After Chemotherapy May Boost Cancer Treatment Response

MedicalResearch.com Interview with:

Professor Frances Balkwill OBE, FMedSci Lead, Centre for Cancer and Inflammation Barts Cancer Institute - a Cancer Research UK Centre of Excellence Queen Mary University of London London

Prof. Frances Balkwill

Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London

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

Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.

We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.

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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

Synergy Between Radiation and Chemotherapy Enhances Melanoma Treatment

MedicalResearch.com Interview with:

James S. Welsh, MS, MD, FACRO President, American College of Radiation Oncology Professor and Medical Director Director of Clinical & Translational Research Department of Radiation Oncology Stritch School of Medicine Loyola University- Chicago Cardinal Bernardin Cancer Center Maguire Center, Rm 2932 Maywood, IL 60153 Chief of Radiation Oncology Hines VA Medical Center

Dr. James Welsh

James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center

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

Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.

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Aromatase Inhibitors Do Not Increase Risk of the Most Fatal Cardiovascular Events in Breast Cancer Patients

MedicalResearch.com Interview with:

Reina Haque, PhD, MPH Research scientist Department of Research & Evaluation Kaiser Permanente Southern California Pasadena Calif

Dr. Reina Haque

Reina Haque, PhD MPH
Research scientist
Kaiser Permanente Southern California Department of Research & Evaluation

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

Dr. Haque: The study fills an important knowledge gap about the long-term association of aromatase inhibitors on cardiovascular disease risk in breast cancer survivors.

This was a retrospective cohort study that included a cohort of 13,273 postmenopausal breast cancer survivors who were diagnosed with breast cancer, either estrogen or progesterone receptor positive, from 1991 to 2010. The patients were followed through 2011, or a maximum of 21 years. The study participants were divided into four groups based on the drugs they received: 31.7 percent were treated only with tamoxifen; 28.6 percent only with aromatase inhibitors; 20.2 percent used both; and 19.4 percent did not use any of these drugs. These oral drugs are used to combat breast cancer recurrence, but may have long-term side effects on other organs.

The study determined that the risk of cardiac ischemia (which can lead to a heart attack) and stroke were not elevated in patients who only took aromatase inhibitors compared to those who only took tamoxifen. These results provide reassurance that aromatase inhibitors may not increase risk of the potentially fatal cardiovascular outcomes compared to tamoxifen.

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Ponatinib Currently Not Indicated As First Line CML Chronic Phase Therapy

MedicalResearch.com Interview with:

Prof Jeffrey H Lipton, PhD, MD, FRCPC  Princess Margaret Cancer Centre Toronto, ON Canada

Prof. Jeffrey Lipton

Prof Jeffrey H Lipton, PhD, MD, FRCPC
Princess Margaret Cancer Centre
Toronto, ON Canada

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

Dr. Lipton: Ponatinib is a third generation tyrosine kinase inhibitor that has been shown to be extremely effective in treating patients with chronic myeloid leukemia resistant to other drugs.  Because of this, it was decided to look at it in newly diagnosed patients in a randomized study against imatinib.  The study was terminated prematurely because of evidence of vascular toxicity that became evident in the phase 1 and 2 studies of ponatinib in previously treated patients with resistant disease.   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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Adjuvant Chemotherapy Improves Survival After Pancreatic Cancer Resection

MedicalResearch.com Interview with:

Alexander A. Parikh, M.D., M.P.H. Associate Professor of Surgery Director of Hepatobiliary, Pancreatic and GI Surgical Oncology Director, Vanderbilt Pancreas Center Vanderbilt University Medical Center Nashville, TN

Dr. Alexander Parikh

Alexander A. Parikh, M.D., M.P.H.
Associate Professor of Surgery
Director of Hepatobiliary, Pancreatic and GI Surgical Oncology
Director, Vanderbilt Pancreas Center
Vanderbilt University Medical Center
Nashville, TN

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

Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease.

The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival.

MedicalResearch.com: What are the main findings?

Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival.

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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

Genetic Assay Oncotype Dx Helps Clarify Chemotherapy Decisions in HER2 Negative Breast Cancer

MedicalResearch.com Interview with:

Oleg Gluz, MD West German Study Group Breast Center Niederrhein Evangelical Hospital Bethesda Moenchengladbach, Germany

Dr. Oleg Gluz

Oleg Gluz, MD
West German Study Group
Breast Center Niederrhein
Evangelical Hospital Bethesda
Moenchengladbach, Germany

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

Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients.

For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk.

MedicalResearch.com: What are the main findings?

Dr. Gluz: The study has two major findings:

We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67).

Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up.

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Breast Cancer Patients Report More Treatment Side Effects Than Their Physicians Recognize

MedicalResearch.com Interview with:
Filippo Montemurro, M.D.

Director, Investigative Clinical Oncology (INCO)
Fondazione del Piemonte per l’Oncologia
Candiolo Cancer Institute (IRCCS)
Torino, Italy

Medical Research: What is the background for this study?

Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The “indirectness” of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended.

Based on these premises, we designed a study to pursue two aims;

  • the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
  • the second was to compare doctors and patients reports of toxicities at corresponding time-points.

Medical Research: What are the main findings?

Dr. Montemurro: We administered the 10-item questionnaire after the first and third cycle of adjuvant chemotherapy to 601 women who had undergone surgery for breast cancer. To develop this questionnaire, CTCAE definitions of severity for each item (nausea, vomiting, constipation, anorexia, dysgeusia, diarrhea, fatigue, pain, paresthesia, and dyspnea) were translated into Italian and rephrased into statements. Patients were asked to choose the statement that best represented the worst experience with that side effect after the reference cycle of chemotherapy. At the same time-points, research nurses extracted information from the medical charts and reported them in paired doctor questionnaires. A total of 99% and 97% of the patient returned filled in questionnaires. Pairwise comparisons showed that doctors systematically underestimated both incidence and severity for all the side effects. Interestingly, comparison of the two patient questionnaires revealed temporal changes that were possibly related to the effect of prophylactic measures taken after the first cycle (i.e. reduction in vomiting, diarrhea and pain) or to cumulative toxicties (i.e. worsening dysgeusia and dyspnea). No such changes except for worsening dyspnea were observed comparing the two doctors questionnaires. Finally, we found a direct relationship between number of patients and magnitude of discrepancy in side effects reporting was observed, suggesting that the workload could be a factor influencing this phenomenon.

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Delaying Chemotherapy After Breast Cancer Surgery Can Decrease Survival

Mariana Chavez Mac Gregor, MD, MSC Assistant Professor, Tenure track Department of Health Services Research Division of Cancer Prevention The University of Texas MD Anderson Cancer Center Houston, TX

Dr. Chavez-MacGregor

MedicalResearch.com Interview with:
Mariana Chavez Mac Gregor, MD, MSC
Assistant Professor
Breast Medical Oncology Department
Health Services Research Department
The University of Texas MD Anderson Cancer Center

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

Dr. Chavez Mac Gregor: Adjuvant chemotherapy has proven to significantly decrease the risk of recurrence among breast cancer patients, however the optimal time to start adjuvant chemotherpay remains unknown. There are biological resasons to believe that a delay in the initiation of systemic therapy can be associated with adverse outcomes. In this large study we evaluated the impact of a delay in the initiation of time to chemotherapy (TTC).  We analyzed data from 24,843 patients with invasive breast cancer (stages I to III) from the California Cancer Registry and observed that compared with patients who received chemotherapy within 31 days of surgery,  no adverse outcomes were associated with time to chemotherapy of 31 to 90 days of surgery. However, there was  a 34 % increase in the risk of death and a 27% increase in the risk of breast cancer specific death  among patients who started  chemotherapy 91 or more days after surgery. In a stratified analysis according to breast cancer subtype, patients with triple-negative breast cancer, a TTC greater than 91 days  was  significantly  associated with worse overall and breast cancer-specific survival.

In addition we evaluated factors associated with delays in  time to chemotherapy (defined as > or = 91 days) and observed that many of the factors are sociodemographic in nature including low socioeconomic status, non-private insurance, and being Hispanic or African American.

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More Nail Inflammation With Second Generation Cancer Treatment with EGFR TKIs

Chia-Yu Chu, MD, PhD Associate Professor, Department of Dermatology National Taiwan University Hospital

Dr. Chia-Yu Chu

MedicalResearch.com Interview with:
Chia-Yu Chu, MD, PhD

Associate Professor, Department of Dermatology
National Taiwan University Hospital

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

Dr. Chia-Yu Chu: It has been well known that EGFR TKIs could cause skin toxicities (acneiform eruptions, pruritus, xerosis and paronychia). However, incidences of these skin toxicities have varied according to the different clinical trials, some of which even simply use “skin rash” instead of specific cutaneous findings in the reports.

Afatinib, in contrast to first generation EGFR TKIs like gefitinib and erlotinib, is a second generation EGFR TKI with irreversible inhibition to not only EGFR, but also HER2 and ErbB4. Whether afatinib cause more skin toxicities remained unknown.

Many of our patients received 2 or even 3 different EGFR TKIs with adequate drug exposure and washout period. Therefore, we had an opportunity to compare skin toxicities in “same patients” receiving different EGFR TKIs, and we found that around 30% of patients receiving afatinib developed paronychia whereas only 10% in gefetinib or erlotinib. This was the only significant difference between the 3 drugs. We also found afatinib treated patients needed significantly more dermatologic visits within 180 days of treatments and the reason was due to higher incidence of afatinib-related paronychia. Interestingly, regardless of causative agents, once skin toxicities developed they could be managed effectively in the same manners.

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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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Denosumab Improves Disease Free Survival in Hormone Receptor Positive Breast Cancer

Director and Chairman Department of Surgery President, Austrian Breast&Colorectal Cancer Study Group Head, Breast Health Center Vienna Comprehensive Cancer Center Vienna Medical University of Vienna - Department of Surgery Austria

Prof. Michael Gnant

MedicalResearch.com Interview with:
Professor Michael Gnant, M.D., FASC

Director and Chairman
Department of Surgery
President, Austrian Breast&Colorectal Cancer Study Group
Head, Breast Health Center Vienna
Comprehensive Cancer Center Vienna
Medical University of Vienna – Department of Surgery
Austria

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

Response: The background of this presentation is as follows: For many years, we have seen intriguing – but also sometimes conflicting – results of trials using adjuvant bone-targeted therapy.

ABCSG-18 is a placebo-controlled trial of adjuvant denosumab 60mg twice yearly, and I have been able to present to you at this year’s ASCO meeting the dramatic reduction in clinical fractures which was the primary end point of the trial. We have also showed that twice yearly denosumab can be administered without added toxicity in this double-blind placebo-controlled trial. These results were as well published in the Lancet earlier this year.

The obvious question remaining now is whether adjuvant treatment with the anti-RANK ligand antibody also improves outcomes in a way similar to what bisphosphonates do.

Main findings of ABCSG-18: disease-free survival results of the intention-to-treat analysis: In the placebo group, we observed 203 DFS events. In the denosumab group, there were 167 DFS events, resulting in a hazard ratio of 0.816, indicating an 18% relative DFS improvement by denosumab. In terms of absolute differences, the benefit was 1.2% at 3 years, 2.1% at 5 years, and 3.1% at 7 years.

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Triplet Therapy Induces Durable Response In Refractory Myeloma

MedicalResearch.com Interview with:
Dr. Ajai Chari MD
Associate Professor
Medicine, Hematology and Medical Oncology
Tisch Cancer Institute
Mount Sinai School of Medicine
New York, NY

Medical Research: What is the background for this study?

Dr. Chari: This is a heavily pretreated population where the median progression free survival (PFS) of the pomalidomide dexamethasone is only 4 months and ORR is only 31%. While the anti CD38 monoclonal antibody daratumumab has single agent has activity in this setting, patients with rapidly progressive disease need combination therapy to achieve rapid and deep responses. Pomalidomide also upregulates CD38 on MM cells and like daratumumab, increases the effector cell activity against myeloma. Thus, there is a strong preclinical and clinical rationale for combining daratumumab with pomalidomide and dexamethasone.

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Patient Specific Drug Combinations Improve AML Treatment

MedicalResearch.com Interview with:
Jeffrey Tyner, Ph.D.
Assistant Professor in Cell, Developmental and Cancer Biology at the Oregon Health & Science University School of Medicine and researcher and OHSU Knight Cancer Institute
Stephen Kurtz, Ph.D.
Research Assistant Professor at the Oregon Health & Science University School of Medicine Leukemia Center and researcher
OHSU Knight Cancer Institute

What is the background for this study? What are the main findings? 

Dr. Tyner: This study was one of many resulting from the ‘Beat AML’ initiative. Acute myeloid leukemia (AML) is a complex form of leukemia; less than 25 percent of newly diagnosed AML patients survive beyond five years. Led by the Knight Cancer Institute at Oregon Health & Science University and The Leukemia & Lymphoma Society (LLS), Beat AML brings together academic health centers and biopharmaceutical companies to accelerate discoveries to improve outcomes for patients with acute myeloid leukemia.

In this study, by using a unique method to test drugs used together, we identified drug combinations that are active against leukemia cells in a patient-specific manner.

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MRI Screening and Treatment Options Improve Survival for Triple Negative Breast Cancer

Dr. Franca Podo, Dr Sci Former Director of the Molecular and Cellular Imaging Unit Department of Cell Biology and Neurosciences Istituto Superiore di Sanità Rome, Italy

Dr. Podo

MedicalResearch.com Interview with:
Dr. Franca Podo, Dr Sci
Former Director of the Molecular and Cellular Imaging Unit
Department of Cell Biology and Neurosciences
Istituto Superiore di Sanità
Rome, Italy

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

Dr. Podo: Population-based studies showed that triple negative breast cancers (TNBCs), i.e. those which are negative for estrogen and progesterone receptors without HER-2/neu overexpression, have a more aggressive clinical course and a 2-to-3 fold higher likelihood of distant recurrence and death from breast cancer within 5 years from diagnosis, compared with non-TNBCs.

In a study published in Clinical Cancer Research (Online First 26 October 2015) Dr. F. Podo and Dr. F. Santoro (Istituto Superiore di Sanità, Rome) and Prof. F. Sardanelli (Università degli Studi di Milano, IRCCS Policlinico San Donato) in collaboration with other Italian co-authors, compared phenotype features and survival rates of invasive TNBCs versus non-TNBCs detected during the HIBCRIT-1 screening study of 501 asymptomatic women at high genetic-familial risk for breast cancer. The screening included BRCA1 and BRCA2 mutation carriers, as well as women with a strong family history of breast and/or ovarian cancer, enrolled between 2000 and 2008 in 18 centers. Data analysis from a median 9.7-year follow-up until June 2015 showed that, combining an annual screening including magnetic resonance imaging (MRI) with adequate treatment options, the mean 5-year overall survival of triple negative breast cancers was not significantly different from that of non-TNBCs (86% vs 93%), in spite of a 3-fold higher rate of cases of grade 3 invasive ductal carcinoma in the former subgroup (71% in TNBCs vs 23% in non-TNBCs). The mean disease-free survival rates were also very similar (77% vs 76%, respectively).

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Plasma cfDNA Can Monitor Response To Metastatic Colon Cancer Treatment

Van K. Morris, M.D. Assistant Professor, GI Medical Oncology University of Texas – M.D. Anderson Cancer Center Houston, TX 77030

Dr. Morris

MedicalResearch.com Interview with:
Van K. Morris,  M.D.
Assistant Professor, GI Medical Oncology
University of Texas – M.D. Anderson Cancer Center
Houston, TX 77030 

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

Dr. Van K Morris: BRAF V600E mutations are associated with poor clinical outcomes for patients with metastatic colorectal cancer.  Patients were enrolled in a phase I clinical trial with the BRAF inhibitor vemurafenib, the anti-EGFR antibody cetuximab, and irinotecan.  Blood  samples were collected every two weeks with each dose, and plasma was analyzed for changes in the fraction of mutant BRAF V600E allele relative to wild-type BRAF allele with time.  Trends in circulating free DNA (cfDNA) changes were compared with radiographic changes by RECIST 1.1 criteria to examine this technique as a marker for response to therapy.

For patients who had a response radiographically, drastic reductions in the BRAF V600E allele fraction were observed even after two weeks of starting therapy, well before the first restaging scan.  Patients who did not have responses radiographically had less  dramatic changes relative to baseline in the BRAF V600E allele fraction.  This technique analyzing cfDNA from plasma was validated using two different approaches – digital droplet PCR and next-generation sequencing by Guardant Health.  Sequencing of cfDNA was also compared in pretreatment and post-progression samples, and novel mutations in MEK1 and GNAS were observed uniquely in post-progression samples.

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Combination Therapy Effective Against Mantle Cell Lymphoma

Jia Ruan, M.D., Ph.D. Associate Professor of Clinical Medicine Weill Cornell Medicine Lymphoma Program Division of Hematology & Medical Oncology New York, NY 10021MedicalResearch.com Interview with:
Jia Ruan, M.D., Ph.D.
Associate Professor of Clinical Medicine
Weill Cornell Medicine
Lymphoma Program
Division of Hematology & Medical Oncology
New York, NY 10021

 

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

Dr. Ruan: Mantle cell lymphoma is an uncommon subtype of non-Hodgkin lymphoma that primarily affects elderly populations. Conventional chemotherapy regimens are generally not curative, and may not be tolerated by many patients, underscoring the need for treatment alternatives.  Previous experience with immunomodulatory compound lenalidomide has shown favorable activity and was well tolerated in patients with relapsedMantle cell lymphoma.  We evaluated the efficacy and safety of the biologic combination with lenalidomide plus rituximab as initial treatment for mantle-cell lymphoma (MCL).

The main findings of the study showed that the combination was effective and generally well tolerated when given as induction and maintenance treatment. The overall response rate was 92%, with complete response rate of 64% in the 36 evaluable patients. Median duration of response has not been reached at a median follow up of 30 months.   Treatment was outpatient-based and quality-of-life was preserved for most patients.

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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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PD-1 Blocker Extends Lives in Lung Cancer Patients

David E. Gerber, MD Associate Professor Division of Hematology-Oncology Associate Director for Clinical Research Co-Leader, Experimental Therapeutics Program Co-Director, Lung Disease Oriented Team Harold C. Simmons Cancer Center University of Texas Southwestern Medical Center Dallas, TXMedicalResearch.com Interview with:
David E. Gerber, MD

Associate Professor
Division of Hematology-Oncology
Associate Director for Clinical Research
Co-Leader, Experimental Therapeutics Program
Co-Director, Lung Disease Oriented Team
Harold C. Simmons Cancer Center
University of Texas Southwestern Medical Center
Dallas, TX

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

Dr. Gerber: In this trial, we compared an immunotherapy and a chemotherapy drug in patients with non-squamous non-small cell lung cancer (NSCLC) whose disease continued to progress after first-line chemotherapy. We found that nivolumab immunotherapy improved overall survival compared to docetaxel chemotherapy and was generally well tolerated. These results are significant because options for patients whose lung cancer progresses after initial treatment are limited.

Nivolumab is an immunotherapy drug that works by inhibiting the cellular pathway known as PD-1 protein on cells that block the body’s immune system from attacking cancerous cells.  The idea behind nivolumab and other immunotherapy drugs is to kick-start the body’s natural immune response to a cancer. Cancer develops and grows in part because it has put the brakes on the immune response. These drugs take the foot off the brake, allowing the immune system to accelerate and attack the cancer.

The phase 3 clinical trial followed more than 500 patients who had non-squamous non-small cell lung cancer (NSCLC): 287 received nivolumab and 268 received the chemotherapy drug docetaxel. The one-year survival rate was 51 percent in the nivolumab arm versus 39 percent in the docetaxel arm. The most common reported side effects with nivolumab were fatigue, nausea, decreased appetite, and weakness, and they were less severe than with docetaxel treatment. In a minority of cases, patients treated with nivolumab also developed autoimmune toxicities affecting various organs.

In addition to studying safety and efficacy, the trial examined the protein biomarker PD-L1, which is believed to play a role in suppressing the immune system. The study results suggested that patients with a higher level of PD-L1 in their cancers may experience the greatest benefit from nivolumab, which targets the related molecule PD1. Using a biomarker helps oncologists predict which patients will do best on which treatment, and plan their treatment accordingly. Other promising predictive biomarkers for cancer immunotherapies include the degree of immune cell infiltration within a tumor and the number of mutations a tumor has.

Specifically, the more mutations a cancer has, the more foreign it appears to the body, thus marking it for immune attack. With lung cancer, we see the greatest number of tumor mutations – and perhaps the greatest benefit from immunotherapy – among individuals with the heaviest smoking history.

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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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Gene Mutation May Be Key to Melanoma Chemotherapy Sensitivity

Rutao Cui M. D., Ph. D.  Vice Chair, Professor,  Department of Pharmacology and Experimental Therapeutic Associate Professor of Pharmacology and Dermatology, and Member The Cancer Center Director The Laboratory of Skin Cancer Therapeutics (LSCT) Boston UniversityMedicalResearch.com Interview with:
Rutao Cui M. D., Ph. D. 
Vice Chair, Professor
Department of Pharmacology and Experimental Therapeutic
Associate Professor of Pharmacology and Dermatology, and Member The Cancer Center
Director The Laboratory of Skin Cancer Therapeutics (LSCT)
Boston University

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

Dr. Cui: Recent studies have revealed that the APC/CCdh1 E3 ubiquitin ligase may function as a tumor suppressor. However, the tumor suppressor role of APC/CCdh1 in melanoma remains largely unclear. Here, we report sporadic mutations occurring in APC components, including Cdh1 in human melanoma samples and that loss of APC/CCdh1 may predispose human melanomagenesis.

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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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Chemotherapy and Radiation For Brain Cancer Lead To Brain Shrinkage

Jorg Dietrich, MBA MMSc MD PhD Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program Massachusetts General Hospital Cancer Center Assistant Professor of Neurology Harvard Medical SchoolMedicalResearch.com Interview with:
Jorg Dietrich, MBA MMSc MD PhD 
Director, Cancer & Neurotoxicity Clinic and Brain Repair Research Program
Massachusetts General Hospital Cancer Center
Assistant Professor of Neurology
Harvard Medical School

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

Dr. Dietrich: Understanding the adverse effects associated with cancer therapy is an important issue in oncology. Specifically, management of acute and delayed neurotoxicity of chemotherapy and radiation in brain cancer patients has been challenging. There is an unmet clinical need to better characterize the effects of standard cancer therapy on the normal brain and to identify patients at risk of developing neurotoxicity. In this regard, identifying novel biomarkers of neurotoxicity is essential to develop strategies to protect the brain and promote repair of treatment-induced damage.

In this study, we demonstrate that standard chemotherapy and radiation in patients treated for glioblastoma is associated with progressive brain volume loss and damage to gray matter – the area of the brain that contains most neurons.

A cohort of 14 patients underwent sequential magnetic resonance imaging studies prior to, during and following standard chemoradiation to characterize the pattern of structural changes that occur as a consequence of treatment.

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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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