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, Chemotherapy, Lung Cancer, NEJM, UT Southwestern / 11.10.2015

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. (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, Chemotherapy, Genetic Research, Melanoma / 04.09.2015

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. (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, Biomarkers, Brain Cancer - Brain Tumors, Chemotherapy, Neurology, Radiation Therapy / 20.08.2015

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. (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, Chemotherapy / 03.06.2015

Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, BelgiumMedicalResearch.com Interview with: Professor Patrick Schöffski Head, Department of General Medical Oncology and the Laboratory of Experimental Oncology at the University Hospital Leuven, KU Leuven, Belgium MedicalResearch: What are the key points of the study? Professor Schöffski: This is the first and only randomised controlled trial of a single agent systemic therapy to demonstrate an improvement in overall survival in people previously treated for advanced soft tissue sarcomas. The study met its primary objective for overall survival benefit (OS) for investigational use in patients treated with eribulin compared to dacarbazine. Median OS for eribulin was 13.5 months versus 11.5 months for dacarbazine representing a significant benefit, meaning that patients treated with eribulin may have a 23% reduction in the risk of death. Furthermore, an additional study endpoint included progression-free survival (PFS) at 12 weeks.  While there was a numerical difference between arms favouring eribulin versus dacarbazine (33% vs 29%) this was not statistically significant. Median PFS was 2.6 months in both arms. (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, Cancer Research, Chemotherapy, JNCI, MD Anderson, Ovarian Cancer / 26.05.2015

Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030MedicalResearch.com Interview with: Wei Zhang, Ph.D., Professor Department of Pathology Director, Cancer Genomics Core Lab University of Texas MD Anderson Cancer Center Houston, Texas 77030 Medical Research: What is the background for this study? What are the main findings? Dr. Zhang: Epithelial ovarian cancer remains the most lethal gynecological malignancy. The 5-year survival rate for patients with advanced ovarian cancer is only 30-40%, and acquired resistance to platinum is considered a major factor in disease relapse. A major challenge in cancer treatment is the resilient ability of cancer cells to repair DNA damage caused by chemotherapy agents.  In this study, we found that adding a molecule called miR-506 to standard chemotherapy can help cells overcome drug resistance, so that the chemotherapy drugs remain effective against ovarian cancer. This research supports a new combination approach, which may substantially benefit patients with this deadly disease. (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, 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, Chemotherapy, Colon Cancer / 13.11.2014

MedicalResearch.com Interview with: Xianglin L. Du, MB, MS, Ph.D.  Professor of Epidemiology, Department of Epidemiology, Human Genetics, and Environmental Sciences, The University of Texas School of Public Health, Houston, TX 77030, USA. Medical Research: What is the background for this study? Dr. Du: Widespread use of screening and advances in screening strategies played a key role in colorectal cancer survival improvement. With the increasing evidence on the benefit of fecal occult blood test and sigmoidoscopy during 1990s, the U.S. Preventive Service Task Force for the first time in 1996 recommended the annual use of fecal occult blood test, periodic use of sigmoidoscopy, or routine use of both modalities for all persons aged 50 or older. Because colonoscopy is able to detect lesions in the entire colon and has a high sensitivity for lesions of over 10mm in size, Medicare began to cover colonoscopy since 2001 for individuals with average-risk of colorectal cancer. Advances in chemotherapy, particularly some new therapeutic regimens approved by Food and Drug Administration (FDA) over the past decades also played a key role in survival improvement for patients with colorectal cancer. However, the overall impact of newly approved chemotherapy regimens on survival in population-based elderly patients remains unclear. It is also unknown what proportion of survival improvement was attributable to changes in tumor stage and size due to screening, and what proportion was attributable to more effective chemotherapy regimens. Hence, we studied a large nationwide and population-based cohort of elderly colorectal cancer patients to examine the changes in tumor stage and tumor size from 1992 to 2009, and to further quantify the effects of changes in stage/size and chemotherapy regimens on improved survival over the two decades. (more…)
Author Interviews, Breast Cancer, Case Western, Chemotherapy / 10.11.2014

Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center Case Western Reserve UniversityMedicalResearch.com Interview with: Ruth Keri, PhD, Professor and Vice Chair Department of Pharmacology Case Western Reserve University School of Medicine, and Associate Director for Basic Research in the Case Comprehensive Cancer Center  Case Western Reserve University Medical Research: What is the background for this study? Dr. Keri: Over the last several decades, the discovery of targeted therapies for certain types of breast cancer, and their use in the clinic, have greatly improved the long-term outcome of patients. Yet some breast cancers don’t respond to these therapies, and ones that do often become resistant over time, resulting in patient relapse and metastatic disease. Why does resistance occur? There are many tricks a tumor employs to evade death. When a drug targets a certain protein or pathway the cancer cell relies on for survival, one potential route of resistance is the cancer cell’s ability to adapt and find another pathway to maintain growth. We reasoned that targeting two separate proteins or pathways important for cancer cell growth may be more effective at preventing or delaying this adaptation. (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, Chemotherapy / 30.10.2014

Melissa Skala, Ph.D. Assistant Professor of Biomedical Engineering Assistant Professor of Cancer Biology Vanderbilt University Nashville, TN 372MedicalResearch Interview with: Melissa Skala, Ph.D. Assistant Professor of Biomedical Engineering Assistant Professor of Cancer Biology Vanderbilt University Nashville, TN 37235 Medical Research: What is the background for this study? What are the main findings? Dr. Skala: We developed a new metabolic imaging technique that is highly sensitive to tumor cell response to anti-cancer drug treatment. We coupled this imaging technique with new, three-dimensional cultures that can be grown from breast tumor biopsies. Together, our data indicate that this approach could be used to perform rapid, low-cost, and accurate drug screens for individualized treatment of cancer patients. (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…)
Chemotherapy / 29.09.2014

Giuseppe Curigliano M.D. Ph.D. Medico Direttore, Director Divisione Sviluppo Nuovi Farmaci per Terapie Innovative Early Drug Development for Innovative Therapies Division Via Ripamonti, MilanoMedicalResearch.com Interview with: Giuseppe Curigliano M.D. Ph.D. Medico Direttore, Director Divisione Sviluppo Nuovi Farmaci per Terapie Innovative Early Drug Development for Innovative Therapies Division Via Ripamonti,  Milano Medical Research: What are the main findings of the study? Dr. Curigliano: In the CLEOPATRA study, 808 patients from 25 countries with HER2-positive metastatic breast cancer were randomised to receive first-line placebo/trastuzumab/docetaxel or pertuzumab/trastuzumab/docetaxel. Randomisation was stratified by geographic region and neo/adjuvant chemotherapy. At ESMO 2014 the CLEOPATRA researchers reported results of a final prespecified OS analysis (February 2014). This overall survival (OS) analysis was planned when ≥385 deaths were reported. The log-rank test, stratified by prior treatment status and geographic region, was used to compare OS between arms, applying the threshold of p ≤ 0.0456. Subgroup analyses of OS were performed for stratification factors and other key baseline characteristics.At median follow-up of 50 months (range 0 to 70 months), the statistically significant improvement in OS in favour of pertuzumab/trastuzumab/docetaxel arm was maintained (HR = 0.68, p = 0.0002). Median OS was 40.8 months in the placebo arm and 56.5 months in the pertuzumab arm, with difference of 15.7 months. The PFS in pertuzumab arm was 18.7 vs 12.4 months in placebo arm, HR 0.68 (p < 0.0001). (more…)
Chemotherapy, Lung Cancer / 06.04.2014

Dr. Heather Wakalee MD Associate Professor of Medicine (Oncology) Stanford University Medical CenterMedicalResearch.com Interview with: Dr. Heather Wakalee MD Associate Professor of Medicine (Oncology) Stanford University Medical Center   MedicalResearch.com: What are the main findings of the study? Dr. Wakalee: CO-1686, with the new hydrobromide formulation, has been active at multiple dose levels (500, 750 or 1000 mg orally twice daily). The response rate in patients with EGFR mutant (non-small-cell Lung Cancer) NSCLC that has progressed after therapy with EGFR TKI, and has centrally confirmed T790M, is 64% per RECIST.  The majority of responses are ongoing at the time of this report.  The drug has been overall very well tolerated. (more…)
Aging, Author Interviews, Breast Cancer, Chemotherapy, JNCI / 30.03.2014

Hanna Sanoff MD, MPH Lineberger Comprehensive Cancer Center Department of Medicine University of North Carolina, Chapel Hill, NCMedicalResearch.com Interview with: Hanna Sanoff MD, MPH Lineberger Comprehensive Cancer Center Department of Medicine University of North Carolina, Chapel Hill, NC MedicalResearch.com: What are the main findings of the study? Dr. Sanoff: We measured p16, a protein that increases with cellular aging, in blood cells of women receiving chemotherapy for breast cancer. We found that a standard course of chemotherapy led to an increase in p16 expression equivalent to what we have previous seen in people over the course of 10-15 years of chronological aging. This increase persisted in cancer survivors an average of three and half years after treatment. (more…)