Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Cognitive Issues / 03.11.2015

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. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research, NEJM / 29.09.2015

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%. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer / 28.09.2015

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, 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. (more…)
Author Interviews, Biomarkers, Cancer Research / 03.09.2015

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. (more…)
Author Interviews, Chemotherapy, Journal Clinical Oncology / 25.08.2015

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. (more…)
Author Interviews, Chemotherapy, Lancet / 17.08.2015

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. (more…)
Author Interviews, Chemotherapy / 24.07.2015

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. (more…)
Author Interviews, Cancer, Cancer Research, Chemotherapy / 10.07.2015

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. (more…)
Author Interviews, Biomarkers, Chemotherapy, Nature, Pancreatic / 01.07.2015

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. (more…)
Author Interviews, Biomarkers, Chemotherapy, JAMA, Johns Hopkins, Prostate Cancer / 08.06.2015

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. (more…)
ASCO, Author Interviews, Biomarkers, Cancer Research / 06.06.2015

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. (more…)
ASCO, Author Interviews, Cancer Research, Chemotherapy, Genetic Research / 03.06.2015

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. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Journal Clinical Oncology, Stanford / 13.05.2015

MedicalResearch.com Interview with: Melinda L. Telli, M.D. Assistant Professor of Medicine Stanford University Division of Medical Oncology Stanford, CAMelinda 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. (more…)
Author Interviews, Cancer Research, UCSF / 03.04.2015

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. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 31.03.2015

Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, ChinaMedicalResearch.com Interview with: Prof Xi-Chun Hu, Department of Oncology Shanghai Medical College Fudan University, Shanghai 200032, China MedicalResearch: What is the background for this study? What are the main findings? Prof. Hu: Triple-negative breast cancer (TNBC) is associated with higher rates of recurrence, shorter disease free survival, and poorer overall survival. Molecular targeting agents tried against Triple-negative breast cancer have nearly all failed. TNBC, concordant with BRCA-associated and basal-like breast cancer, has abnormal DNA repair and genome-wide instability, supporting the use of DNA-damaging agents such as platinum. However, platinum monotherapy is not very potent, combination with other agents, such as gemcitabine has a synergistic effect. The GP regimen could be an alternative or even preferential first-line doublet chemotherapy strategy for patients with mTNBC. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Cleveland Clinic, NEJM / 04.03.2015

Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195MedicalResearch.com Interview with: Halle C.F. Moore, M.D. Cleveland Clinic Foundation Taussig Cancer Institute Cleveland, OH 44195 Medical Research: What is the background for this study? What are the main findings? Dr. Moore: Ovarian failure is a common long-term side effect of chemotherapy. Previous studies investigating whether suppressing ovarian function during chemotherapy treatment will preserve ovarian function following chemotherapy have had mixed results. Our study found that suppressing the ovaries with the GnRH analog goserelin during chemotherapy treatment for early stage ER-negative breast cancer resulted in a reduced risk of ovarian failure two years after initiation of treatment. Also, more women who received the goserelin with chemotherapy became pregnant than women who received chemotherapy without goserelin. In addition, there was an apparent improvement in survival among the goserelin group, confirming the safety of this approach in this patient population. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Lancet / 04.03.2015

MedicalResearch.com Interview with: Dr. Lucia Del Mastro MD Department of Medical Oncology Istituto Nazionale per la Ricerca sul Cancro Genova, Italy Medical Research: What is the background for this study? What are the main findings? Response: Adjuvant chemotherapy regimens with anthracyclines and taxanes improve the outcome of patients with early breast cancer. Among the most widely used anthracycline-based chemotherapy in sequential combinations with the taxane paclitaxel (P) there are epirubicin and cyclophosphamide (EC) and fluorouracil, epirubicin, and cyclophosphamide (FEC). The contribution of fluorouracil to the anthracycline-cyclophosphamide regimen (EC) was unclear until now. Various randomized trials attempted to assess the role of a more intense schedule of chemotherapy (i.e. dose-dense chemotherapy with cycles administered every 2 weeks instead of every 3 weeks) in patients with early breast cancer. However, most of these trials compared dose-dense chemotherapy with regimens that use standard intervals but with different drugs or dose in the treatment groups, thus making difficult to extrapolate the true role of the dose-dense strategy. The results of GIM2 study show that the addition of fluorouracil to  a sequential regimen with epirubicin, cyclophosphamide and paclitaxel increases the toxicity, in terms of neutropenia, fever, nausea, and vomiting, and is not associated with an improved outcome compared with the same treatment without fluorouracil. (more…)
Author Interviews, Chemotherapy, JAMA, Leukemia, Neurological Disorders / 25.02.2015

William E. Evans, Pharm.D. Member, Pharmaceutical Sciences St. Jude Children’s Research HospitalMedicalResearch.com Interview with: William E. Evans, Pharm.D. Member, Pharmaceutical Sciences St. Jude Children’s Research Hospital MedicalResearch: What is the background for this study? What are the main findings? Dr. Evans: We are currently curing over 85 percent of children with acute lymphoblastic leukemia (ALL), the most common cancer in children. While we continue to focus on pushing cure rates closer to 100 percent through the development of new treatments, we are also increasingly focused on reducing the acute and chronic side effects of treatment. This is important to improve the quality of life for patients during treatment and as they become adults after being cured, because some side effects can persist for decades after treatment is completed. One of the medications that every child with acute lymphoblastic leukemia received 30-40 times during their 2+ years of treatment is vincristine. The major side effect of vincristine is peripheral neuropathy (about 25 percent of patients develop this side effect), which can cause loss of sensation, numbness, neuropathic pain and alter their motor skills including manual dexterity, balance and ability to walk properly. This can have very practical consequences, such as writing, using a smart phone, and the use of eating utensils. It can also alter their gait. Our main finding is we discovered that an inherited variant of the CEP72 gene enhanced the risk and severity of vincristine neuropathy in two groups of patients we studied. Those children who inherited two copies of the high-risk CEP72 gene (one from each parent, about 16 percent of patients) had a significantly higher likelihood (about 3.5-fold) of developing vincristine neuropathy and had a more severe form of neuropathy (about 2.5-fold higher severity). The CEP72 gene encodes a protein essential for normal microtubule formation in cells—a critical process for cell division. Vincristine inhibits this same cellular process. The inherited form of CEP72 that increases the risk and severity of vincristine neuropathy is associated with lower expression of the CEP72 protein. When coupled with vincristine treatment, CEP72 increases a cell’s sensitivity to vincristine. We were able to reproduce this in the laboratory by lowering CEP72 expression in human neurons made from induced pluripotent stem cells and in human leukemia cells, increasing the sensitivity of both to vincristine. We also showed that the leukemia cells from patients who inherited two copies of the CEP72 risk allele were more sensitive to vincristine, suggesting it may be possible to treat these patients with a lower dose of vincristine to reduce their neuropathy without compromising the treatment of their leukemia—a possibility we plan to test in our next clinical trial at St. Jude. (more…)
Author Interviews, Cancer Research / 11.02.2015

MedicalResearch.com Interview with: Dr. Dixie-Lee Esseltine MD, FRCPC Vice President, Oncology Clinical Research Takeda. MedicalResearch: What is Ixazomib? Dr. Dixie-Lee Esseltine: Ixazomib is an investigational, oral, once-weekly proteasome inhibitor (PI) that is being investigated in multiple Phase 3 trials in multiple myeloma (MM) and systemic light-chain (AL) amyloidosis. It is the first oral  proteasome inhibitor to enter Phase 3 clinical trials. Proteasome inhibition is a mechanism underpinning an established standard of care in the treatment of multiple myeloma. However, the current biweekly parenteral administration of proteasome inhibitors may pose challenges to patients. The ability to demonstrate that an oral, once-weekly PI can extend PFS would be a remarkably important finding in the effort to address these challenges. Early studies suggest ixazomib, has activity in MM patients, both as a single agent in relapsed patients and in combination in frontline patients. Ixazomib was granted orphan drug designation in multiple myeloma in both the U.S. and Europe in 2011, and for AL amyloidosis in both the U.S. and Europe in 2012. It was granted Breakthrough Therapy Designation for AL amyloidosis in the U.S. in 2014. MedicalResearch: What is the design for this study? Dr. Dixie-Lee Esseltine: The TOURMALINE MM-1 study (C16010) is a phase 3, randomized, double-blind study comparing ixazomib plus lenalidomide and dexamethasone versus placebo plus lenalidomide and dexamethasone in patients with relapsed and/or refractory multiple myeloma. Patients were randomized to receive ixazomib 4.0mg days 1,8 and 15 or placebo with  lenalidomide 25mg days 1-21 and dexamethasone 40mg days 1,8,15 and 22. Treatment was given every 28 days until disease progression or unacceptable toxicity. Evaluation was based on the International Myeloma Working Group (IMWG) Uniform Response Criteria. (more…)
Author Interviews, General Medicine, Journal Clinical Oncology, Leukemia, Pediatrics / 29.01.2015

MedicalResearch.com Interview with: Jun J. Yang  Ph.D. Assistant Member Dept. of Pharm. Sci. St. Jude Children's Research Hospital Memphis, TN 38105 Medical Research: What is the background for this study? What are the main findings? Dr. Yang: Mercaptopurine is highly effective in acute lymphoblastic leukemia (ALL) and essential for the cure of this aggressive cancer. However, it also has a narrow therapeutic index with common toxicities. Identifying genetic risk factors for mercaptopurine toxicity will help us better understand how this drug works and also potentially enable clinicians to individualize therapy based on patients’ genetic make-up (precision medicine). In addition to confirming the role of TPMT, we have identified another important genetic risk factor (a genetic variation in a gene called NUDT15) for mercaptopurine intolerance. Patients carrying the variant version of NUDT15 are exquisitely sensitive and required up to 90% reduction of the normal dose of this drug. TPMT variants are more common in individuals of African and European ancestry, whereas NUDT15 variants are important in East Asians and Hispanics. (more…)
Author Interviews, Chemotherapy, Dermatology / 04.11.2014

N. T. Georgopoulos, PhD Senior Lecturer in Biological Sciences Department of Biological Sciences School of Applied Sciences University of HuddersfieldMedicalResearch.com Interview with: N. T. Georgopoulos, PhD Senior Lecturer in Biological Sciences Department of Biological Sciences School of Applied Sciences University of Huddersfield Medical Research: What is the background for this study? What are the main findings? Dr. Georgopoulos: Chemotherapy-induced alopecia (CIA) is one of the most distressing side effect of chemotherapy and the anxiety caused by the prospect of Chemotherapy-induced alopecia can cause some cancer patients to even refuse treatment. Various classes of chemotherapeutic drugs such as taxanes (e.g. docetaxel), alkylating agents (e.g. cyclophosphamide) and anthracyclines/DNA intercalating agents (e.g. doxorubicin) target tumour cells due to their rapid division rate; however, these drugs also target the hair matrix keratinocytes, the most rapidly dividing cell subset in the hair follicle, thus resulting in follicle damage and ultimately hair loss. The only currently available preventative treatment for Chemotherapy-induced alopecia is head (scalp) cooling; scalp cooling during chemotherapy drug administration can substantially reduce hair loss and has been used since the 1970s. However, until recently there was inadequate biological data to support the cyto-protective capacity of cooling; yet such experimental evidence would be important to convince clinicians and patients of the efficacy of cooling. Moreover, it is not clear why in some patients scalp cooling fully protects from Chemotherapy-induced alopecia whereas in other patients it is less efficient. Finally, although scalp cooling can substantially reduce the incidence of hair loss in response to individual drugs, for some combined treatment regimens scalp cooling has much lower (and often quite limited) reported efficacy. Collectively, the need to answer these questions, and to provide ‘real’ experimental data that will support the ability of cooling to ‘rescue’ cells from the cytotoxic effects of chemotherapy drugs, led us to carry out the study. Using several cell culture models (including human hair follicular keratinocytes), we showed for the first time that cooling dramatically reduces or completely prevents the cytotoxic capacity of drugs such as docetaxel, doxorubicin and the active metabolite of cyclophosphamide (4-OH-CP), whilst combinatorial treatment showed relatively poor response to cooling. Our experimental, in vitro findings are in close agreement with clinical observations. Moreover, we have provided evidence that the minimum temperature achieved may be critical in determining the efficacy of cooling; as the lowest temperature achieved by scalp cooling can differ between patients (our unpublished observations), our findings may also explain why cooling protects from Chemotherapy-induced alopecia better in some patients but not others. (more…)
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy / 27.10.2014

MedicalResearch.com Interview with: Shidong Jiang Associate professor of Engineering Thayer School of Engineering at Dartmouth Medical Research: What is the background for this study? What are the main findings? Dr. Jiang: Breast cancer is the most common non-skin cancer in women worldwide, and the second leading cause of women’s cancer mortality in the United States. A common treatment strategy after diagnosis is to shrink breast cancer tumors larger than 3 centimeters with a 6 to 8 month course of Neoadjuvant Chemotherapy prior to surgery. Clinical studies have shown that patients who respond to Neoadjuvant Chemotherapy have longer disease-free survival rates, but only 20 to 30 percent of patients who receive Neoadjuvant Chemotherapy fit this profile. Our work represents the first clinical evidence that tumor total hemoglobin estimated from DOST images differentiates women with locally advanced breast cancer who have a complete pathological response with Neoadjuvant Chemotherapy from those who do not with predictive significance based on image data acquired before the initiation of therapy. The implication of this prognostic information is that certain tumors are pre-disposed to responding to Neoadjuvant Chemotherapy, and that this predisposition should be known prior to choosing the therapy.  The study also demonstrates the potential of dramatically accelerating the validation of optimal Neoadjuvant Chemotherapy regimes through future randomized clinical trials by reducing the number of patients required and the length of time they need to be followed by using a validated imaging surrogate as an outcome measure. (more…)
Author Interviews, Breast Cancer, Chemotherapy, Journal Clinical Oncology, Mayo Clinic / 21.10.2014

dr_edith_perezMedicalResearch.com Interview with: Edith A. Perez, MD Mayo Clinic Jacksonville, FL 32224 Medical Research: What are the main findings of the study? Dr. Perez: Our joint analysis of two large prospective trials showed that adding one year of Trastuzumab to otherwise standard adjuvant chemotherapy significantly improved long term survival in women with resected HER2+ breast cancer. (more…)
Author Interviews, Cancer Research, Herpes Viruses, Vaccine Studies / 06.08.2014

Sara Tartof, PhD, MPH Post-doctoral research fellow Kaiser Permanente Southern California Department of Research & Evaluation.MedicalResearch.com Interview with: Sara Tartof, PhD, MPH Post-doctoral research fellow Kaiser Permanente Southern California Department of Research & Evaluation. Medical Research: What are the main findings of the study? Dr. Tartof: Our study found that the herpes zoster vaccine continues to be effective in protecting older adults against shingles, even after they undergo chemotherapy. In particular, we found that those patients who were previously vaccinated with the vaccine were 42 percent less likely to develop shingles following chemotherapy treatment. We also found that none of our vaccinated patients underwent hospitalization for shingles, while six unvaccinated patients were hospitalized with the disease. (more…)
Pancreatic / 10.07.2014

Andrea Wang-GillamMD, PhD Assistant Professor, Department of Medicine Oncology Division, Medical Oncology Section Washington University School of Medicine in St. LouisMedicalResearch.com Interview with: Andrea Wang-GillamMD, PhD Assistant Professor, Department of Medicine Oncology Division, Medical Oncology Section Washington University School of Medicine in St. Louis Medical Research: What are the main findings of the study? Dr. Wang-Gillam: This is a global randomized phase III trial of MM398 plus 5FU/LV vs. MM398 vs. 5FU/LV in patients with metastatic pancreatic cancer who had received prior gemcitabine-based therapy. The primary endpoint was overall survival (OS). The secondary endpoints included progression-free survival (PFS), response rate (RR), biochemical response and safety. The trial achieved its primary endpoint. The median overall survival was statistically longer with the combination of MM398 plus 5FU/LV compared with 5FU/LV alone (6.1 months vs 4.2 months; HR of 0.67; p=0.0122). A superior progression-free survival was also seen in the MM398 plus 5FU/LV group compared with the 5FU/LV alone group (3.1 months vs 1.5 months; HR of 0.56; p=0.0001). A higher response rate was observed in the combination regimen compared with the 5FU/LV group (16% vs 1%). There were no differences in overall survival or PFS between the MM 398 monotherapy and 5FU/LV groups. (more…)
Author Interviews, BMJ, Cancer Research, Chemotherapy, End of Life Care / 05.03.2014

Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Co-Director, Center for End-of-Life Research Weill Cornell Medical College New York Presbyterian Hospital New York City, New York 10065MedicalResearch.com Interview with: Holly G. Prigerson, Ph.D. Irving Sherwood Wright Professor in Geriatrics Professor of Sociology in Medicine Co-Director, Center for End-of-Life Research Weill Cornell Medical College New York Presbyterian Hospital New York City, New York 10065 MedicalResearch.com: What are the main findings of the study? Dr. Prigerson: The main outcome of the research was end-of-life treatment and location of death with secondary outcomes being length of survival, late hospice referrals and attainment of preferred place of death. We found that 56 percent of patients receiving palliative chemotherapy in their final months.  Patients treated with palliative chemotherapy were five to 10 times more likely to receive intensive medical care and to die in an intensive care unit (ICU). Fewer than half died at home as compared with two-thirds of patients with metastatic cancer not treated with palliative chemotherapy. More specifically, we found that palliative chemotherapy was associated with:
  • Increased use of CPR and mechanical ventilation: 14% versus 2%
  • Late hospice referral: 54% versus 37%
  • Death in an ICU: 11% versus 2%
  • Death away from home: 47% versus 66%
  • Death away from their preferred place: 65% versus 80%
Survival did not differ significantly between patients who received palliative chemotherapy and those who did not (hazard ratio 1.11, 95% CI 0.90-1.38). Additionally, patients receiving palliative chemotherapy were less likely to acknowledge their illness as terminal (35% versus 49%, P=0.04), to have discussed end-of-life wishes with a physician (37% versus 48%, P=0.03), and to have completed a do-not-resuscitate order (36% versus 49%, P<0.05). (more…)
Author Interviews, Cancer Research, Chemotherapy, NEJM / 20.02.2014

Krishnansu S. Tewari, MD, FACOG, FACS| Professor & Director of Research Principal Investigator - The Gynecologic Oncology Group at UC Irvine The Division of Gynecologic Oncology University of California, Irvine Medical Center Orange, CA 92868MedicalResearch.com Interview with: Krishnansu S. Tewari, MD, FACOG, FACS| Professor & Director of Research Principal Investigator - The Gynecologic Oncology Group at UC Irvine, Division of Gynecologic Oncology University of California, Irvine Medical Center Orange, CA 92868 MedicalResearch.com: What are the main findings of the study? Dr. Tewari: The main findings of this study were that the addition of bevacizumab to chemotherapy resulted in a significantly improved survival of 3.7 months in a population of patients that have very limited options. This improvement in overall survival was not accompanied by any significant deterioration in quality of life and serious side effects were limited to 3% to 8% of the study population. (more…)
Author Interviews, Chemotherapy, Compliance / 16.12.2013

Dawn L. Hershman, MD MS Associate Professor of Medicine and MedicalResearch.com Interview with: Dawn L. Hershman, MD MS Associate Professor of Medicine and Epidemiology Leader, Breast Cancer Program Herbert Irving Comprehensive Cancer Center Columbia University Medical Center MedicalResearch.com: What are the main findings of the study? Dr. Hershman: We have found in the past that compliance to 5 years of hormone therapy for the adjuvant treatment of breast cancer is low. While toxicity is a main reason, other factors are also important. Recent studies suggest out of pocket costs are high among cancer patients. We evaluated the change in adherence to hormone therapy after the introduction of generic Aromatase inhibitors. We found that discontinuation decreased and adherence increased with generic aromatase inhibitors compared to brand name. we found that higher co-payments were associated with decreased adherence and increased discontinuation. We also found that patients in the highest income group were more likely to be adherent to hormone therapy. (more…)