Chemotherapy
18 Oct Abraxane Demonstrates Benefit Over Paclitaxel in Metastatic Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_28991" align="alignleft" width="200"]
Dr. Corey Pelletier[/caption]
Corey Pelletier PhD
Director, Health Economics & Outcomes Research
Celgene Corporation
Summit, NJ
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In a phase III clinical trial, ABRAXANE demonstrated significant improvement in ORR vs paclitaxel in patients with metastatic breast cancer. Celgene initiated this study because limited data exist on the comparative effectiveness of ABRAXANE vs paclitaxel for patients with metastatic breast cancer, including HR+/HER2- and triple negative (TN) metastatic breast cancer (MBC), in a real-world setting. This study used a U.S. based electronic medical record (EMR) dataset to evaluate the real-world comparative effectiveness of second-line ABRAXANE vs paclitaxel in patients with MBC and included patients with HR+/HER2- or TN MBC. This study also assessed adverse events and use of supportive care in this patient population.
The median time to treatment discontinuation (TTD) for ABRAXANE vs paclitaxel was 4.50 vs 2.83 months (adjusted P<0.0001*) in all patients. Patients with HR+/HER2- or TN MBC had similar TTD. The median time to next treatment (TTNT) in all patients was 5.9 vs 4.2 months (adjusted P=0.2140*) for ABRAXANE vs paclitaxel, respectively. Patients receiving ABRAXANE had less fatigue, neuropathy, and anemia compared to patients receiving paclitaxel. Patients treated with ABRAXANE also used less antiemetics, and had fewer treatments for hydration or allergic reaction compared to those treated with paclitaxel. Patients treated with paclitaxel used less GCSF and had fewer treatments for bone loss compared to those treated with ABRAXANE.
*TTD and TTNT were adjusted for age, number of metastases, targeted agent use, adjunctive chemotherapy, HER2 status, TN status, and CCI score without age.
13 Sep Lung Cancer: Adjusting Afatinib Dose Reduced Side Effects With No Impact on Efficacy
MedicalResearch.com Interview with: [caption id="attachment_27869" align="alignleft" width="95"]
Dr. Chih-Hsin Yang[/caption]
Chih-Hsin Yang MD PhD
Department of Oncology
National Taiwan University Hospital
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: LUX-Lung 3 and LUX-Lung 6 are multicenter, randomized, open-label, Phase III trials of afatinib versus chemotherapy (pemetrexed / cisplatin and gemcitabine / cisplatin, respectively) as first-line treatment for patients with EGFR mutation-positive, advanced and metastatic non-small-cell lung cancer (NSCLC). Both trials met their primary endpoint of PFS with afatinib significantly delaying tumor growth when compared to standard chemotherapy.
A post-hoc analysis of the studies was conducted to look at the incidence and severity of common adverse events (AEs) before and after afatinib dose reduction and the PFS was compared between patients who dose reduced within the first 6 months of treatment and those who did not.
The results showed dose reductions were associated with decreases in the incidence and severity of treatment-related AEs, while median progression-free survival (PFS) was similar in patients who dose-reduced within the first six months of treatment versus those who did not (LUX-Lung 3, 11.3 vs 11 months; LUX-Lung 6, 12.3 vs 11 months).
30 Aug Docetaxel Adds To Overall Survival in Metastatic Castration-Resistant Prostate Cancer
MedicalResearch.com Interview with: Prof. Ronald de Wit, MD, PhD Medical Oncologist Medical Oncology Erasmus MC University Medical Center, Rotterdam MedicalResearch.com: What is the background for this study? What are the main findings? Response: Mainsail is one of the largest phase 3 trials in the setting of Metastatic Castration-Resistant Prostate Cancer (mCRPC) in the past decade that investigated the addition of a second active biological drug to standard docetaxel every 3 weeks plus prednisone. In Mainsail the greater myelotoxicity caused by the addition of lenalidomide to docetaxel resulted in a reduction of the number of cycles of docetaxel that patients were able to tolerate – median of 6 cycles in the DPL arm vs. 8 in the DP arm. Median overall survival (OS) was shorter in patients receiving lenalidomide, which could have attributed to either a direct adverse effect of lenalidomide on OS, or, alternatively because of the reduction in the number of docetaxel treatment cycles. In this study we investigated the impact of the cumulative dose of docetaxel as reflected by the total number of cycles of docetaxel on median OS, in Univariate and Multivariate analyses on the ITT Population, both dependent upon the treatment arm, as well as irrespective of the treatment arm. In subsequent sensitivity analyses we addressed potential confounding factors on the eventual survival outcome.26 Aug 70-Gene Signature Can Help Identify Early-Stage Breast Cancer Patients Who Do Not Need Chemotherapy
MedicalResearch.com Interview with: [caption id="attachment_27366" align="alignleft" width="150"]
Dr. Laura Van't Leer[/caption]
Prof. Laura van ’t Veer, PhD
Leader, Breast Oncology Program, and Director, Applied Genomics, UCSF Helen Diller Family Comprehensive Cancer Center
Angela and Shu Kai Chan Endowed Chair in Cancer Research
UCSF Helen Diller Family Comprehensive Cancer Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: MINDACT was designed to involve only patients with node negative and 1 to 3 positive lymph node breast cancer. Node negative breast cancer is a cancer that has not spread to the surrounding lymph nodes and therefore has a lower risk of recurrence. Scientists have also demonstrated that breast cancer which has spread to 1 to 3 lymph nodes may behave like node negative breast cancer. Patients with either node negative cancer or with a cancer that involves 1-3 lymph nodes are often prescribed chemotherapy, although physicians believe that approximately 15% of them do not require such treatment.
MINDACT provides the highest level of evidence to show that using MammaPrint® can substantially reduce the use of chemotherapy in patients with node-negative and 1-to-3 node positive breast cancer – in other words, it can identify patients with these types of breast cancer who can safely be spared a treatment that may cause significant side effects, and will offer no to very little benefit.
25 Aug Capecitabine Cancer Treatment Can Result in Loss of Fingerprints
MedicalResearch.com Interview with: [caption id="attachment_27352" align="alignleft" width="96"]
Leni van Doorn[/caption]
Leni van Doorn, MSc
Department of Medical Oncology
Erasmus MC Cancer Institute
Rotterdam, the Netherlands
MedicalResearch.com: What is the background for this study?
Response: The common cancer treatment capecitabine, a regular treatment for patients mostly diagnosed with breast-, colon- or gastic cancer, induces hand foot syndrome (HFS). HFS is a cutaneous condition that may lead to red palms and blisters in approximately 50% to 60% of the patients and is believed to result in the loss of fingerprints. This fingerprint loss has been described sporadically in the literature.
The main aim of our prospective study was to have a closer look of the association between hand foot syndrome and the loss of fingerprints.
25 Aug Breast Cancer Cells Can Switch HER2 On and Off, Requiring Combination Treatment
Posted at 01:29h
in Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Chemotherapy, Nature
MedicalResearch.com Interview with:
[caption id="attachment_27306" align="alignleft" width="125"]
Dr. Shyamala Maheswaran[/caption]
Shyamala Maheswaran, PhD
Associate Professor of Surgery
Harvard Medical School
Assistant Molecular Biologist
Center for Cancer Research
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: About 85% hormone receptor positive HER2 negative metastatic breast cancer patients show that cancer cells acquire HER2 expression during disease progression. These HER2 positive cells coexist with HER2 negative cancer cells, and these two populations are able to spontaneously oscillate between these two states; in culture and in cancers established in mice. Both HER2 positive and HER2 negative cells form tumors when injected into mice, but HER2 positive cancer cells form tumors more rapidly than HER2 negative tumors. At a molecular level, several growth factor pathways are activated in HER2 positive cancer cells, while activation of the Notch pathway, an embryonic signaling event, is observed in HER2 negative cells. Thus the HER2 positive and HER2 negative cancer cells exhibit differential sensitive to drugs: the HER2 positive cells, which are more proliferative and non-responsive to HER2-targeting agents, are responsive to chemotherapy drugs whereas the HER2 negative tumor cells are sensitive to Notch inhibitors. A combination of chemotherapeutic drugs and notch inhibitors effectively eliminate tumors formed by a mixture of these two population of cancer cells compared to either drug alone. These findings highlight the importance of tumor heterogeneity in cancer progression and drug responses and suggest that targeting all the different populations within cancers is necessary to effectively manage cancer progression.
11 Aug Pancreatic Cancer Study Finds Abraxane Superior to Paclitaxel
MedicalResearch.com Interview with: [caption id="attachment_26931" align="alignleft" width="200"]
Dr. Rajesh Kumar NV[/caption]
Rajesh Kumar NV, Ph.D.
Instructor of Oncology and Pathology
Johns Hopkins University School of Medicine
Baltimore, MD, USA
Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA
MedicalResearch.com: What is the background for this study?
Response: Pancreatic cancer remains as one of the most deadly malignancies in the world. Recently, a cremophor-free and albumin-bound formulation of paclitaxel (nab-PTX, Abraxane) in combination with gemcitabine (GEM, Gemzar) is recently approved as a standard of care treatment option for patients with metastatic pancreatic cancer. Majority of the newly diagnosed pancreatic cancer patients use the nab-PTX plus GEM regimen. Currently there are over 100 clinical trials at various stages with this regimen as a backbone to approved medicines or investigational agents. Since widely available cremophor-based paclitaxel (PTX, Taxol) is a key chemotherapy component for the treatment of several human malignancies and the treatment cost of nab-PTX is relatively higher than PTX, patients, clinicians, third party payers and regulatory agencies have a substantial interest in understanding whether these two drugs provide a similar level of therapeutic efficacy in pancreatic cancer.
We utilized orthotopic models of human pancreatic cancer, which were shown to better recapitulate the histologic and metastatic characteristics of disease, and compared the anticancer efficacy, effect on tumor stroma modulation, metastatic spreading to distant organs and survival following GEM, PTX, nab-PTX and combinations of GEM plus PTX or nab-PTX. The preclinical trial used a total of 300 mice with established orthotopic pancreatic tumors. The tumors used for implantation were originally resected from the primary tumors of patients with moderately differentiated and poorly differentiated pancreatic cancer.
27 Jul Sticky Hydrogel Can Deliver Triple Therapy Directly To A Tumor
MedicalResearch.com Interview with: [caption id="attachment_26504" align="alignleft" width="157"]
Dr. Natalie Artzi[/caption]
Natalie Artzi PhD
Assistant Professor at Brigham and Women’s Hospital, Harvard Medical School
Associate member of the Broad Institute of Harvard and MIT.
MedicalResearch.com: What is the background for this study?
Response: We have shown in the last years that dendrimer:dextran adhesive hydrogels represent a platform with ahuge potential for delivery. In 2015, we were able to report that these gels doped with smart nanoparticles could sense and differentially react with the disease microenvironment (e.g. can sense the tissue microenvironment by detecting the expression of specific genes related with multidrug resistance, Conde et al. PNAS 2015), potentiating targeted drug release and uptake in certain disease settings.
Later, these hydrogels prove to be incredibly useful for miRNA delivery by using the self-assembly of a triple-helix forming miRNA structure that lead to nearly 90% levels of tumor shrinkage two weeks post-gel implantation (Conde et al. Nature Materials 2016a).
Here, we took a step-forward, and used these hydrogels to develop a prophylactic patch for gene, chemo and phototherapy in a triple-combination approach to achieve complete tumor resection when applied to non-resected tumors and to the absence of tumor recurrence when applied following tumor resection (Conde et al. Nature Materials 2016b). This study also identifies the molecular and genetic pathways triggered in response to the three therapeutic modalities − photo-, gene- and chemo-therapy − by tumor gene expression profiling in treated mice.
13 Jul Promising Study Evaluates Chemotherapy for Parkinson’s and Lewy Body Dementia
MedicalResearch.com Interview with: [caption id="attachment_26087" align="alignleft" width="133"]
Dr. Charbel Moussa[/caption]
Charbel Moussa MD. PhD
Assistant Professor of Neurology
Director- Laboratory for Dementia and Parkinsonism
Clinical Research Director- National Parkinson's Foundation Center for Excellence
Translational Neurotherapeutics Program
Department of Neurology
Georgetown University Medical Center
Washington DC.
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We conducted a pilot open label proof-of-concept study to evaluate the safety and tolerability of Nilotinib in participants with advanced Parkinson’s disease (PD) with dementia (PDD) or dementia with Lewy bodies (DLB). Our primary objective is to demonstrate that low oral daily doses of 150mg or 300mg Nilotinib (compared to 600-800mg in cancer) are safe and tolerated.
Our secondary objectives are that Nilotinib will cross the blood brain barier and may inhibit cerebral spinal fluid Abl. Based on preclinical data we also hypothesized that Nilotinib will increase DA levels. Motor and cognitive functions were also measured as exploratory clinical outcomes. Other exploratory outcomes are that Nilotinib may alter PD-related CSF biomarkers DJ-1 and α-synuclein. As most participants in this study had dementia we also explored the effects of Nilotinib on Alzheimer's Disease-related CSF biomarkers, including Aβ40 and Aβ42, total tau and phosphorylated tau (p-tau).
22 Jun Adding Plinabulin To Chemotherapy Reduces Toxicity, Improves Efficacy
MedicalResearch.com Interview with: [caption id="attachment_25414" align="alignleft" width="133"]
Dr. Lan Huang[/caption]
Dr. Lan Huang PhD
Co-founder, Chairman and CEO
BeyondSpring Pharmaceuticals, Inc
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The background for this study is the toxicity of Docetaxel chemotherapy causes inadequate dosing with Docetaxel due to dose delay, reduction or discontinuation, thus leaving the patient with inadequate chemotherapy treatment.
A main finding is a statistically significant p value of 0.002 in lower rates of grade 3 and 4 Neutropenia for patients dosed with a combination of BeyondSpring’s Plinabulin and Docetaxel compared to those patients dosed with Docetaxel alone. As a result, approximately 14 percent more patients stayed on the adequate (dense) dose of Docetaxel in the Docetaxel + Plinabulin arm as compared to Docetaxel alone.
15 Jun Cardiovascular Risks More Common With Newer TKI Chemotherapeutics for CML
Posted at 15:54h
in Annals Internal Medicine, Author Interviews, Chemotherapy, Heart Disease, Karolinski Institute, Leukemia
MedicalResearch.com Interview with:
Torsten Dahlén MD
Centre for Hematology
Karolinska University Hospital Solna
Stockholm Sweden
MedicalResearch.com: What is the background for this study?
Dr. Dahlén: Patients diagnosed with CML have had a dramatic increase in life-expectancy since the widespread introduction of tyrosine kinase inhibitors (TKI) in 2001. However, treatment is today regarded as life-long. We thus need to observe for late-effects of continuous TKI exposure. Recent reports have demonstrated a linkage between TKI treatment, especially more potent 2nd and 3rd generation drugs, and to the occurrence of peripheral arterial occlusive disease (PAOD). This study aimed to use real-world data utilizing Swedish population based registries together with the dedicated Swedish CML registry which contains data and follow-up on more than 98% of all CML patients diagnosed in Sweden since 2002.
15 Jun Immunotherapy After Chemotherapy May Boost Cancer Treatment Response
MedicalResearch.com Interview with: [caption id="attachment_25195" align="alignleft" width="138"]
Prof. Frances Balkwill[/caption]
Professor Frances Balkwill OBE, FMedSci
Lead, Centre for Cancer and Inflammation
Barts Cancer Institute
Queen Mary University of London
London
MedicalResearch.com: What is the background for this study?
Prof. Balkwill: We wanted to find out if chemotherapy altered patients immune system especially the immune cells that co-exist with cancer cells in tumors.
We studied women with ovarian cancer who often receive chemotherapy after diagnosis but before surgery. This meant, at least in some of them, we could study a biopsy taken before treatment began and also a biopsy taken during the operation.
06 Jun Risk Factors of Chemotherapy Induced Peripheral Neuropathy Identified
MedicalResearch.com Interview with: [caption id="attachment_24778" align="alignleft" width="130"]
Dr. Dawn Hershman[/caption]
Dawn L. Hershman, MD MS
Professor of Medicine and Epidemiology
Leader, Breast Cancer Program
Herbert Irving Comprehensive Cancer Center
Columbia University
NY NY
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Hershman: Chemotherapy induced peripheral neuropathy is a common side effect of anti cancer therapy and there are currently no ways to prevent it. We used a large clinical trials database, SWOG, and linked it to Medicare claims for patients over the age of 65. We found that age and type of taxane were associated with the development of CIPN. We also found a significant increase when a taxane was given along with a platinum agent. We found a doubling of risk among patients with a prior history of diabetes. No other chronic condition was associated with an increased risk of CIPN. We found a suggestion of a decreased risk among patients with a prior history of auto-immune disease.
27 May ChemoBrain Linked to Decreased Dopamine Release
MedicalResearch.com Interview with: [caption id="attachment_24738" align="alignleft" width="160"]
Dr. Michael Johnson[/caption]
Michael A. Johnson Ph.D
Associate Professor
Department of Chemistry
University of Kansas
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Johnson: We undertook these studies because chemotherapy induced cognitive dysfunction, also known as ‘chemobrain’, has become a major health issue in recent years. For example, up to a third of patients who have undergone chemotherapy treatment for breast cancer have reported symptoms of chemobrain. These symptoms may include loss of verbal and visual memory as well as decreased mental flexibility and difficulty focusing.
For this study, we wanted to understand how treatment with chemotherapeutic agents affects the ability of neurons to communicate. An impairment of neurotransmitter release would imply that communication is hindered. This inability to communicate normally could contribute to cognitive dysfunction.
We initially measured the release of dopamine in a region of the brain called the striatum. Our measurement of dopamine in this region was motivated by two key issues: its importance in cognitive function and our ability to measure it with high temporal resolution. From a cognitive standpoint, dopamine is important because the striatum helps translate signals, received from the cortex, into plans by forwarding wanted signals to other parts of the brain and suppressing unwanted signals. Fortunately, we can easily measure dopamine release using an electrochemical technique called fast-scan cyclic voltammetry. This method allows us to not only measure how much dopamine is released from a living brain slice, but also it affords us the capability to measure how quickly dopamine is taken back up. We also measured serotonin release using this method.
Our main finding was that the ability of neurons to release dopamine was impaired after carboplatin treatment. We also found that serotonin release was similarly impaired. These release impairments corresponded to a decrease in cognitive ability of the treated rats.
24 May Heating Chemotherapy For Bladder Cancer Treatment May Increase Efficacy
MedicalResearch.com Interview with: [caption id="attachment_24650" align="alignleft" width="198"]
Dr. Alejandro Sousa[/caption]
Alejandro Sousa, MD, PhD
Department of Urology, Comarcal Hospital
Monforte, Spain
MedicalResearch.com: What is the background for this study?
Dr. Sousa: Bladder Cancer management has remained stable over the past 25 years, with very little in the way of new therapies or approaches being developed. Traditional treatment using intravesical Mitomycin C for Non Muscle Invasive Bladder Cancer (NMIBC) patients is limited due it's low absorption levels. Device assisted therapies that deliver Chemo-hyperthermia offer a new hope, with the potential for improved outcomes and better disease management due the the increased drug activity and better efficacy. We wanted to investigate the optimal treatment regime for this new therapy and whether it provides a safe and effective alternative to current standard treatment.
24 May Synergy Between Radiation and Chemotherapy Enhances Melanoma Treatment
MedicalResearch.com Interview with: [caption id="attachment_24628" align="alignleft" width="165"]
Dr. James Welsh[/caption]
James S. Welsh, MS, MD, FACRO
President, American College of Radiation Oncology
Professor and Medical Director
Director of Clinical & Translational Research
Department of Radiation Oncology
Stritch School of Medicine Loyola University- Chicago
Cardinal Bernardin Cancer Center
Maywood, IL 60153
Chief of Radiation Oncology
Hines VA Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Welsh: Cancer immunotherapy could represent a truly powerful means of addressing cancer. Although immunotherapy itself is not new, there are new agents and combinations of older agents (including radiation therapy) that could prove more successful than anything we have seen in many years. The data in melanoma thus far is quite encouraging and this preliminary success could possibly extend to many other malignancies as well.
04 May Aromatase Inhibitors Do Not Increase Risk of the Most Fatal Cardiovascular Events in Breast Cancer Patients
Posted at 18:13h
in Author Interviews, Breast Cancer, Chemotherapy, Heart Disease, Kaiser Permanente
MedicalResearch.com Interview with:
[caption id="attachment_19768" align="alignleft" width="156"]
Dr. Reina Haque[/caption]
Reina Haque, PhD MPH
Research scientist
Kaiser Permanente Southern California Department of Research & Evaluation
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Haque: The study fills an important knowledge gap about the long-term association of aromatase inhibitors on cardiovascular disease risk in breast cancer survivors.
This was a retrospective cohort study that included a cohort of 13,273 postmenopausal breast cancer survivors who were diagnosed with breast cancer, either estrogen or progesterone receptor positive, from 1991 to 2010. The patients were followed through 2011, or a maximum of 21 years. The study participants were divided into four groups based on the drugs they received: 31.7 percent were treated only with tamoxifen; 28.6 percent only with aromatase inhibitors; 20.2 percent used both; and 19.4 percent did not use any of these drugs. These oral drugs are used to combat breast cancer recurrence, but may have long-term side effects on other organs.
The study determined that the risk of cardiac ischemia (which can lead to a heart attack) and stroke were not elevated in patients who only took aromatase inhibitors compared to those who only took tamoxifen. These results provide reassurance that aromatase inhibitors may not increase risk of the potentially fatal cardiovascular outcomes compared to tamoxifen.
13 Apr Ponatinib Currently Not Indicated As First Line CML Chronic Phase Therapy
MedicalResearch.com Interview with: [caption id="attachment_23424" align="alignleft" width="136"]
Prof. Jeffrey Lipton[/caption]
Prof Jeffrey H Lipton, PhD, MD, FRCPC
Princess Margaret Cancer Centre
Toronto, ON Canada
MedicalResearch.com: What is the background and purpose for this study?
Dr. Lipton: Ponatinib is a third generation tyrosine kinase inhibitor that has been shown to be extremely effective in treating patients with chronic myeloid leukemia resistant to other drugs. Because of this, it was decided to look at it in newly diagnosed patients in a randomized study against imatinib. The study was terminated prematurely because of evidence of vascular toxicity that became evident in the phase 1 and 2 studies of ponatinib in previously treated patients with resistant disease.
08 Mar Fosaprepitant reduces chemoradiotherapy-induced emesis in patients treated for cervical cancer
MedicalResearch.com Interview with: Dr Christina H Ruhlmann PhD Department of Oncology Odense University Hospital, Denmark MedicalResearch.com: What is the background for this study? Response: The background for the GAND-emesis study is the result of a phase II study in patients with gynecological cancer receiving fractionated radiotherapy and concomitant weekly cisplatin 40 mg/m2. In that study, patients received weekly antiemetic prophylaxis with palonosetron and prednisolone, and we found that 57% of patients were continuously free from emesis (sustained no emesis) during 5 weeks of treatment. We hypothesized that the addition of a NK1 receptor antagonist could increase the number of patients with sustained no emesis, and we therefore planned the GAND-emesis study: a multinational, randomised, placebo-controlled, double-blind study that has recently been published. MedicalResearch.com: What are the main findings? Response: In the GAND-emesis study we compared efficacy of weekly antiemetic prophylaxis with fosaprepitant, palonosetron, and dexamethasone to placebo, palonosetron, and dexamethasone during 5 weeks of radiotherapy and concomitant weekly cisplatin 40 mg/m2 for cervical cancer. The primary endpoint was sustained no emesis during 5 weeks of treatment (competing risk analysis). We found that the proportion of patients with sustained no emesis was 48.7% for the placebo group compared with 65.7% for the fosaprepitant group, and the treatments were well tolerated. To our knowledge, this is the first study to investigate the efficacy of a NK1 receptor antagonist during 5 weeks of chemoradiotherapy.07 Mar Adjuvant Chemotherapy Improves Survival After Pancreatic Cancer Resection
MedicalResearch.com Interview with: [caption id="attachment_22400" align="alignleft" width="129"]
Dr. Alexander Parikh[/caption]
Alexander A. Parikh, M.D., M.P.H.
Associate Professor of Surgery
Director of Hepatobiliary, Pancreatic and GI Surgical Oncology
Director, Vanderbilt Pancreas Center
Vanderbilt University Medical Center
Nashville, TN
MedicalResearch.com: What is the background for this study?
Dr. Parikh: Although adjuvant chemotherapy has been proven to increase survival after successful resection of pancreatic cancer and has become the standard of care worldwide, the use of adjuvant chemoradiation is more controversial. The vast majority of randomized trials have failed to show a significant improvement in survival with the use of chemoradiation after pancreatic cancer resection. Furthermore, our own report from the multi-institutional Central Pancreatic Consortium (CPC) published several years ago failed to show a benefit in the use of chemoradiation except in high-risk groups such as lymph node positive disease.
The purpose of the current study was to investigate the patterns of recurrence with the use of adjuvant chemotherapy or chemoradiation in hopes of explaining some of these differences. It was our hypothesis that systemic chemotherapy would prevent distant recurrence (and perhaps local) while chemoradiation would only prevent local recurrence and thereby have less impact on overall survival.
MedicalResearch.com: What are the main findings?
Dr. Parikh: The main findings demonstrated that adjuvant chemotherapy led to an improvement in both local and distant recurrence with a corresponding improvement in overall survival while chemoradiation only led to an improvement in local recurrence but not distant nor overall survival.
04 Mar Patients May Benefit From New Combination Therapy For HER2-Negative Metastatic Breast Cancer
MedicalResearch.com Interview with: [caption id="attachment_22319" align="alignleft" width="200"]
Dr. Massimo Cristofanilli[/caption]
Massimo Cristofanilli, MD, FACP
Professor of Medicine
Associate Director of Translational Research and Precision Medicine
Department of Medicine-Hematology and Oncology
Robert H Lurie Comprehensive Cancer Center
Feinberg School of Medicine
Chicago, IL 60611
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Cristofanilli: The majority of breast cancer are estrogen-receptor positive and therefore candidate for treatment with endocrine therapy in the adjuvant and advanced settings. The most significant issue in the management of estrogen-receptor positive metastatic breast cancer is the development of drug resistance. Very few effective options are available for patients that demonstrate progression of disease while on standard endocrine therapy, particularly in premenopausal women and/or women that have even progressed on chemotherapy. The study demonstrated that the combination of fulvestrant with palbociclib, a novel inhibitor of CDK4/6 kinases, significantly improve response to treatment and delays disease progression with minimal toxicity.
03 Mar Genetic Assay Oncotype Dx Helps Clarify Chemotherapy Decisions in HER2 Negative Breast Cancer
Posted at 12:18h
in ASCO, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy, Genetic Research, Journal Clinical Oncology
MedicalResearch.com Interview with:
[caption id="attachment_22296" align="alignleft" width="200"]
Dr. Oleg Gluz[/caption]
Oleg Gluz, MD
West German Study Group
Breast Center Niederrhein
Evangelical Hospital Bethesda
Moenchengladbach, Germany
MedicalResearch.com: What is the background for this study?
Dr. Gluz: PlanB trial is a Phase III chemotherapy study performed in patients with clinically high risk HER2 negative breast cancer. After early amendement, Recurrence Score (Oncotype Dx) as a selection criterion for or against chemotherapy together with central pathology review were included into the study. Patients with very low RS of below 12 and up to 3 positive lymph nodes were recommended to omit chemotherapy based on the low genomic recurrence risk. Chemotherapy was omitted in about 15% of all patients.
For the first time we present prospective data comparing a genomical tool (Oncotype Dx) and an independent central pathology review for grade, ER, PR, and Ki-67 from a large phase III study combined with an exploratory analysis on early relapse risk.
MedicalResearch.com: What are the main findings?
Dr. Gluz: The study has two major findings:
We have found a significant discordance in risk assessment between prognostic tools (grade by local and central lab, Oncotype Dx, Ki-67).
Patients treated by endocrine therapy alone based on very low Recurrence Score had an excellent disease free survival of 97% after 3 years of follow up.
24 Dec Breast Cancer Patients Report More Treatment Side Effects Than Their Physicians Recognize
MedicalResearch.com Interview with: Filippo Montemurro, M.D. Director, Investigative Clinical Oncology (INCO) Fondazione del Piemonte per l'Oncologia Candiolo Cancer Institute (IRCCS) Torino, Italy Medical Research: What is the background for this study? Dr. Montemurro: The evaluation of treatment-related side effects is a critical step in cancer patient management. It is important in the clinical practice, where the decision to modify doses, omit administrations or establish supportive care measures is based on treatment tolerance and side effects severity and duration. It is also important in the context of clinical trials. In the latter setting, the mere information of the antitumor activity of a new drug or regimen under investigation is worth little if it not accompanied by an accurate reporting of the side effect profile. For this reason, over the years reference protocols to standardize the process of toxicity reporting in clinical trials have been established. The most recent and widespread is the Common Terminology Criteria for Adverse Events (CTCAE), that is issued and constantly updated by the National Cancer Institute. The CTCAE allows the description of the incidence and on the grade of severity on a scale ranging from 0 (no toxicity) to 5 (death due to that toxicity). Normally, the medical or nursing staff data collects information to fill in the CTCAE reports either by interviewing patients or extracting data from the clinical notes taken by physicians. The "indirectness" of this process has consequences that are becoming acknowledged for their potential implications. The incidence and severity of toxicities results often underestimated by doctors when their reports are compared with corresponding reports provided directly by patients without intermediaries (so called Patient reported outcomes-PRO). If this phenomenon is described in the context of clinical trials, it might occur to a greater extent also in the clinical practice, where the process of toxicity reporting is not mandated by a protocol and no reference standard is recommended. Based on these premises, we designed a study to pursue two aims;- the first was to assess whether a 10-item questionnaire derived by the CTCAE could be used by breast cancer patients receiving adjuvant chemotherapy after surgery in the daily clinical practice;
- the second was to compare doctors and patients reports of toxicities at corresponding time-points.
14 Dec Delaying Chemotherapy After Breast Cancer Surgery Can Decrease Survival
[caption id="attachment_19898" align="alignleft" width="200"]
Dr. Chavez-MacGregor[/caption]
MedicalResearch.com Interview with:
Mariana Chavez Mac Gregor, MD, MSC
Assistant Professor
Breast Medical Oncology Department
Health Services Research Department
The University of Texas MD Anderson Cancer Center
Medical Research: What is the background for this study? What are the main findings?
Dr. Chavez Mac Gregor: Adjuvant chemotherapy has proven to significantly decrease the risk of recurrence among breast cancer patients, however the optimal time to start adjuvant chemotherpay remains unknown. There are biological resasons to believe that a delay in the initiation of systemic therapy can be associated with adverse outcomes. In this large study we evaluated the impact of a delay in the initiation of time to chemotherapy (TTC). We analyzed data from 24,843 patients with invasive breast cancer (stages I to III) from the California Cancer Registry and observed that compared with patients who received chemotherapy within 31 days of surgery, no adverse outcomes were associated with time to chemotherapy of 31 to 90 days of surgery. However, there was a 34 % increase in the risk of death and a 27% increase in the risk of breast cancer specific death among patients who started chemotherapy 91 or more days after surgery. In a stratified analysis according to breast cancer subtype, patients with triple-negative breast cancer, a TTC greater than 91 days was significantly associated with worse overall and breast cancer-specific survival.
In addition we evaluated factors associated with delays in time to chemotherapy (defined as > or = 91 days) and observed that many of the factors are sociodemographic in nature including low socioeconomic status, non-private insurance, and being Hispanic or African American.
11 Dec More Nail Inflammation With Second Generation Cancer Treatment with EGFR TKIs
[caption id="attachment_20007" align="alignleft" width="124"]
Dr. Chia-Yu Chu[/caption]
MedicalResearch.com Interview with:
Chia-Yu Chu, MD, PhD
Associate Professor, Department of Dermatology
National Taiwan University Hospital
Medical Research: What is the background for this study? What are the main findings?
Dr. Chia-Yu Chu: It has been well known that EGFR TKIs could cause skin toxicities (acneiform eruptions, pruritus, xerosis and paronychia). However, incidences of these skin toxicities have varied according to the different clinical trials, some of which even simply use “skin rash” instead of specific cutaneous findings in the reports.
Afatinib, in contrast to first generation EGFR TKIs like gefitinib and erlotinib, is a second generation EGFR TKI with irreversible inhibition to not only EGFR, but also HER2 and ErbB4. Whether afatinib cause more skin toxicities remained unknown.
Many of our patients received 2 or even 3 different EGFR TKIs with adequate drug exposure and washout period. Therefore, we had an opportunity to compare skin toxicities in “same patients” receiving different EGFR TKIs, and we found that around 30% of patients receiving afatinib developed paronychia whereas only 10% in gefetinib or erlotinib. This was the only significant difference between the 3 drugs. We also found afatinib treated patients needed significantly more dermatologic visits within 180 days of treatments and the reason was due to higher incidence of afatinib-related paronychia. Interestingly, regardless of causative agents, once skin toxicities developed they could be managed effectively in the same manners.
10 Dec Most Women Not Willing To Take Medications To Prevent Breast Cancer
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Sam Smith, PhD CPsychol[/caption]
MedicalResearch.com Interview with:
Sam Smith, PhD CPsychol
Cancer Research UK Postdoctoral Fellow
Centre for Cancer Prevention
Queen Mary University of London
Wolfson Institute of Preventive Medicine
London
Medical Research: What is the background for this study? What are the main findings?
Dr. Smith: Several trials have demonstrated that agents (e.g. ) can be used to prevent breast cancer among women at increased risk. However, their effectiveness is dependent upon their appropriate use by this patient group. Several studies have suggested that uptake is low, and that women are not taking the medications for the full 5 year course. We attempted to synthesize the evidence investigating these topics, as well as identify the factors affecting these behaviours.
The main findings are that only 1 in 6 women (16.3%) were willing to start taking oral medications to prevent breast cancer.
Furthermore, uptake rates were lower in routine clinical practice (9%) compared with trial enrollment rates (25%), suggesting that there may be problems with implementing chemoprevention within routine clinical care. We noted that day to day adherence and persistence over a short period (e.g. 1 year) was adequate, but when looking at the longer term studies only 1 in 10 reported that >80% of women were still taking their medications at the 5 year end point. Women may not be experiencing the full preventive effect of these medications.
09 Dec Denosumab Improves Disease Free Survival in Hormone Receptor Positive Breast Cancer
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Prof. Michael Gnant[/caption]
MedicalResearch.com Interview with:
Professor Michael Gnant, M.D., FASC
Director and Chairman
Department of Surgery
President, Austrian Breast&Colorectal Cancer Study Group
Head, Breast Health Center Vienna
Comprehensive Cancer Center Vienna
Medical University of Vienna - Department of Surgery
Austria
Medical Research: What is the background for this study? What are the main findings?
Response: The background of this presentation is as follows: For many years, we have seen intriguing - but also sometimes conflicting - results of trials using adjuvant bone-targeted therapy.
ABCSG-18 is a placebo-controlled trial of adjuvant denosumab 60mg twice yearly, and I have been able to present to you at this year’s ASCO meeting the dramatic reduction in clinical fractures which was the primary end point of the trial. We have also showed that twice yearly denosumab can be administered without added toxicity in this double-blind placebo-controlled trial. These results were as well published in the Lancet earlier this year.
The obvious question remaining now is whether adjuvant treatment with the anti-RANK ligand antibody also improves outcomes in a way similar to what bisphosphonates do.
Main findings of ABCSG-18: disease-free survival results of the intention-to-treat analysis: In the placebo group, we observed 203 DFS events. In the denosumab group, there were 167 DFS events, resulting in a hazard ratio of 0.816, indicating an 18% relative DFS improvement by denosumab. In terms of absolute differences, the benefit was 1.2% at 3 years, 2.1% at 5 years, and 3.1% at 7 years.