BTK inhibitors have become an important class of targeted therapies for several blood cancers, including CLL, mantle cell lymphoma, and...
Author Interviews, Cancer Research, Chemotherapy, Melanoma, NYU/NYMC / 27.06.2025
NYU Study Finds Genetic Mitochondrial Trait Confers Resistance to Checkpoint Inhibitors in Melanoma
MedicalResearch.com Interview with:
[caption id="attachment_69251" align="alignleft" width="156"] Dr. Kirchhoff[/caption]
Tomas Kirchhoff, PhD (corresponding author)
Associate ProfessorLaura and Isaac Perlmutter Cancer Center
New York University School of Medicine
Robert Ferguson PhD
Senior Scientist at NYU Langone Medical Center
Kelsey Monson, PhD
Immuno-Oncology Postdoctoral Researcher
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? Would you briefly explain how mitochondrial DNA differs from chromosomal DNA?
TK: Immune checkpoint blockade has changed the way we treat several cancers, including advanced melanoma. Before these therapies, the treatment options were very limited, but now more than half of patients experience significant tumor shrinkage or disease control.
KRM: Despite these advances, many patients still do not respond to treatment. One of the main challenges in cancer medicine today is to find ways to predict which patients will benefit from these therapies before treatment begins. This approach is key to personalizing care and improving outcomes.
RF: Mitochondria are small structures inside our cells that produce the energy needed for cells to function. Unlike most of our DNA, mitochondrial DNA is inherited only from the mother. Scientists can categorize this mitochondrial DNA into groups called haplogroups, based on unique variations in the genetic code. These haplogroups can provide insight into how cells produce energy and may affect a person’s health or response to cancer treatment.
Dr. Kirchhoff[/caption]
Tomas Kirchhoff, PhD (corresponding author)
Associate ProfessorLaura and Isaac Perlmutter Cancer Center
New York University School of Medicine
Robert Ferguson PhD
Senior Scientist at NYU Langone Medical Center
Kelsey Monson, PhD
Immuno-Oncology Postdoctoral Researcher
Icahn School of Medicine at Mount Sinai
MedicalResearch.com: What is the background for this study? Would you briefly explain how mitochondrial DNA differs from chromosomal DNA?
TK: Immune checkpoint blockade has changed the way we treat several cancers, including advanced melanoma. Before these therapies, the treatment options were very limited, but now more than half of patients experience significant tumor shrinkage or disease control.
KRM: Despite these advances, many patients still do not respond to treatment. One of the main challenges in cancer medicine today is to find ways to predict which patients will benefit from these therapies before treatment begins. This approach is key to personalizing care and improving outcomes.
RF: Mitochondria are small structures inside our cells that produce the energy needed for cells to function. Unlike most of our DNA, mitochondrial DNA is inherited only from the mother. Scientists can categorize this mitochondrial DNA into groups called haplogroups, based on unique variations in the genetic code. These haplogroups can provide insight into how cells produce energy and may affect a person’s health or response to cancer treatment.
Cancer Research, Chemotherapy / 26.11.2024
Living With the Unpleasant Side Effects of Cancer Treatment
Cancer treatment has made significant advancements over the years, offering hope and extended lifespans to millions of patients worldwide. However, while these treatments are often life-saving, they can come with a wide range of unpleasant side effects that impact daily living. For many patients, managing these side effects becomes an essential part of the recovery journey. Understanding what to expect, and finding strategies to cope, can help improve quality of life during and after cancer treatment. This article explores common side effects of cancer therapies and offers practical tips for living through these challenges.
[caption id="attachment_65116" align="aligncenter" width="500"] Photo by Thirdman [/caption]
Understanding the Common Side Effects of Cancer Treatment
Cancer treatment can involve various methods, including chemotherapy, radiation therapy, immunotherapy, targeted therapies, and surgery. Each type of treatment comes with its own set of side effects, which can vary in intensity depending on the individual's overall health, type of cancer, and the specific therapy used.
Some of the most common side effects include:
Photo by Thirdman [/caption]
Understanding the Common Side Effects of Cancer Treatment
Cancer treatment can involve various methods, including chemotherapy, radiation therapy, immunotherapy, targeted therapies, and surgery. Each type of treatment comes with its own set of side effects, which can vary in intensity depending on the individual's overall health, type of cancer, and the specific therapy used.
Some of the most common side effects include:
- Fatigue: Fatigue is unfortunately one of the most frequent complaints among cancer patients undergoing treatment. Unlike everyday tiredness, cancer-related fatigue can be severe and persistent, making even simple tasks feel overwhelming.
- Nausea and Vomiting: Chemotherapy and radiation can trigger nausea and vomiting as the body reacts to the aggressive nature of the treatments. While anti-nausea medications can help, these symptoms can still be a significant source of discomfort.
- Hair Loss: Hair loss is a very well-known side effect of many chemotherapy drugs, which target rapidly dividing cells. This can include hair on the scalp as well as eyebrows, eyelashes, and body hair. For many, this physical change can be emotionally challenging.
- Mouth Sores and Dryness: Treatments like chemotherapy and radiation can cause sores in the mouth, making it painful to eat, drink, and even speak. Dry mouth, caused by damage to salivary glands, is another common issue that can interfere with taste and oral comfort.
- Skin Changes: Radiation therapy can lead to skin reactions, including redness, peeling, or darkening of the treated area. Some patients may also experience sensitivity to the sun and a tendency to bruise easily.
- Cognitive Changes ("Chemo Brain"): Many patients experience difficulties with memory, concentration, and mental clarity during and after chemotherapy, a phenomenon often referred to as "chemo brain." This can make it harder to focus on tasks or remember details.
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, JAMA, Yale / 26.11.2020
Breast Cancer: Cost-Effectiveness of Neoadjuvant-Adjuvant Treatment Strategies
MedicalResearch.com Interview with:
[caption id="attachment_56014" align="alignleft" width="191"] Dr. Pusztai[/caption]
Lajos Pusztai, M.D, D.Phil.
Professor of Medicine
Director, Breast Cancer Translational Research
Co-Director, Yale Cancer Center Genetics and Genomics Program
Yale Cancer Center
Yale School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In HER2-positive early stage (stage I-II) breast cancer, several different preoperative (also called neoadjuvant) chemotherapy options exist, each of these is associated with a different rate of complete eradication of cancer from the breast and lymph nodes (called pathologic complete response or pCR). Patients who experience pCR have excellent long term survival. The complete response rates range from 20% to 80%, the rates are higher with regimens that include several different chemotherapy drugs and dual HER2 blockade. Unfortunately, these highly effective multi-drug treatment regimens are also more toxic and more expensive. We also learned that patients who do not achieve pCR after preoperative therapy, have high rates of recurrence, but the recurrence rate can be improved by administering postoperative adjuvant therapy.
These two observations together, (1) different regimens with different toxicities and costs resulting in different pCR rates, and (2) existence of effective postoperative therapies for patients with residual cancer after preoperative therapy, sets the stage for combining various pre- and post-operative treatment strategies. Starting with a shorter, less toxic and less expensive neoadjuvant regimen would allow a substantial minority (20-45%) of patients who archive pCR to be spared of longer and more toxic regimens, whereas those with residual disease could receive the remaining part of the currently most effective regimens post-operatively as adjuvant therapy.
In this study we examined the cost effectiveness of different neoadjuvant followed by adjuvant treatment strategies from a healthcare payer perspective.
Dr. Pusztai[/caption]
Lajos Pusztai, M.D, D.Phil.
Professor of Medicine
Director, Breast Cancer Translational Research
Co-Director, Yale Cancer Center Genetics and Genomics Program
Yale Cancer Center
Yale School of Medicine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In HER2-positive early stage (stage I-II) breast cancer, several different preoperative (also called neoadjuvant) chemotherapy options exist, each of these is associated with a different rate of complete eradication of cancer from the breast and lymph nodes (called pathologic complete response or pCR). Patients who experience pCR have excellent long term survival. The complete response rates range from 20% to 80%, the rates are higher with regimens that include several different chemotherapy drugs and dual HER2 blockade. Unfortunately, these highly effective multi-drug treatment regimens are also more toxic and more expensive. We also learned that patients who do not achieve pCR after preoperative therapy, have high rates of recurrence, but the recurrence rate can be improved by administering postoperative adjuvant therapy.
These two observations together, (1) different regimens with different toxicities and costs resulting in different pCR rates, and (2) existence of effective postoperative therapies for patients with residual cancer after preoperative therapy, sets the stage for combining various pre- and post-operative treatment strategies. Starting with a shorter, less toxic and less expensive neoadjuvant regimen would allow a substantial minority (20-45%) of patients who archive pCR to be spared of longer and more toxic regimens, whereas those with residual disease could receive the remaining part of the currently most effective regimens post-operatively as adjuvant therapy.
In this study we examined the cost effectiveness of different neoadjuvant followed by adjuvant treatment strategies from a healthcare payer perspective.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 04.09.2019
More Cancer Drugs Approved Using Non-Inferiority Trials: What Are the Problems with This Approach?
MedicalResearch.com Interview with:
[caption id="attachment_42572" align="alignleft" width="200"] Dr. Bishal Gyawali[/caption]
Bishal Gyawali, MD, PhD
Department of Medicine
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: Cancer drugs are prescribed to the patients based on results from trials. Usually, these are superiority trials meaning the cancer drugs prove that they are better than the treatment we already have.
Recently, more and more cancer drugs are approved on the basis of non-inferiority trials. In these trials, the cancer drugs only prove that they are not worse than the treatment we already have ( instead of proving they are better). Such an approach is considered justified if the new drug provides any other benefit such as lower cost, easy to administer or improved quality of life.
Dr. Bishal Gyawali[/caption]
Bishal Gyawali, MD, PhD
Department of Medicine
Brigham and Women’s Hospital
MedicalResearch.com: What is the background for this study?
Response: Cancer drugs are prescribed to the patients based on results from trials. Usually, these are superiority trials meaning the cancer drugs prove that they are better than the treatment we already have.
Recently, more and more cancer drugs are approved on the basis of non-inferiority trials. In these trials, the cancer drugs only prove that they are not worse than the treatment we already have ( instead of proving they are better). Such an approach is considered justified if the new drug provides any other benefit such as lower cost, easy to administer or improved quality of life.
Author Interviews, Chemotherapy, Leukemia / 18.06.2019
Acute Myeloid Leukemia: LSD1 Inhibition In Combination With Azacitidine in the Elderly
MedicalResearch.com Interview with:
[caption id="attachment_49825" align="alignleft" width="133"] Dr Buesa[/caption]
Dr. Carlos Buesa PhD
Chief Executive Officer
Oryzon Genomics
MedicalResearch.com: What is the background for this study?
Response: Lysine specific demethylase 1 (LSD1, also known as KDM1A) is a histone modifying enzyme that removes methyl groups, thereby regulates the expression of many genes important in cancer progression and cell proliferation.
Aberrant expression of LSD1 has been shown in many types of cancers. In particular, LSD1 expression is upregulated in bladder, small cell lung (SCLC), and colorectal clinical cancer tissues when compared with the corresponding nonneoplastic tissues. LSD1 has also been shown to be overexpressed in some breast cancers and may function as a biomarker of the aggressiveness of the disease.
However, the function of LSD1 is most understood in acute leukemia, particularly Acute Myeloid Leukemia and Acute Lymphoblastic leukemia. LSD1 is crucial for the function and maintenance of the leukemic stem cells, a subset of malignant cells that is believed to be the ultimate reason for relapse in these patients. LSD1 inhibition might be a therapeutic solution to avoid those relapses.
Dr Buesa[/caption]
Dr. Carlos Buesa PhD
Chief Executive Officer
Oryzon Genomics
MedicalResearch.com: What is the background for this study?
Response: Lysine specific demethylase 1 (LSD1, also known as KDM1A) is a histone modifying enzyme that removes methyl groups, thereby regulates the expression of many genes important in cancer progression and cell proliferation.
Aberrant expression of LSD1 has been shown in many types of cancers. In particular, LSD1 expression is upregulated in bladder, small cell lung (SCLC), and colorectal clinical cancer tissues when compared with the corresponding nonneoplastic tissues. LSD1 has also been shown to be overexpressed in some breast cancers and may function as a biomarker of the aggressiveness of the disease.
However, the function of LSD1 is most understood in acute leukemia, particularly Acute Myeloid Leukemia and Acute Lymphoblastic leukemia. LSD1 is crucial for the function and maintenance of the leukemic stem cells, a subset of malignant cells that is believed to be the ultimate reason for relapse in these patients. LSD1 inhibition might be a therapeutic solution to avoid those relapses.
ASCO, Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Radiation Therapy / 03.06.2019
Older Women With Early Breast Cancer May Have A Choice of Radiation Therapy Alone
MedicalResearch.com Interview with:
[caption id="attachment_49509" align="alignleft" width="130"] Prof. Chadha[/caption]
Manjeet Chadha, MD, MHA, FACR, FASTRO
Prof. Radiation Oncology
Director of the Department of Radiation Oncology
Mount Sinai Downtown
MedicalResearch.com: What is the background for this study?
Response: Largely, the goal of cancer care among the elderly is to de-escalate therapy searching for a modality that is both an effective treatment and also associated with minimal toxicity.
Approximately, 30% of new breast cancers diagnosed annually are among women older than 70 years of age. Age-adjusted trends note a relatively higher incidence of stage I breast cancer in women between the ages of 70-74 years. For this group of patients, it is imperative that we take a closer look at the evidence-base for our current practice standards, and evaluate opportunities to improve cancer care delivery in the elderly.
Randomized trials have helped arrive at an acceptance of adjuvant endocrine monotherapy in older patients with ER positive, node negative breast cancer. However, in the older patients high rates of non-compliance to tamoxifen secondary to poor tolerance is widely recognized. Emerging data also detail the side effect profile of aromatase inhibitors. Most commonly observed symptoms of arthralgia, reduced bone mineral density, and increased risk of fractures throughout the duration of treatment are important considerations for an older population. At least a quarter of patients on aromatase inhibitors discontinue therapy specifically due to skeletal events and musculoskeletal symptoms. Overall, the side effects of ET contribute to a high rate of non-compliance and negative impact on patients’ quality of life.
Prof. Chadha[/caption]
Manjeet Chadha, MD, MHA, FACR, FASTRO
Prof. Radiation Oncology
Director of the Department of Radiation Oncology
Mount Sinai Downtown
MedicalResearch.com: What is the background for this study?
Response: Largely, the goal of cancer care among the elderly is to de-escalate therapy searching for a modality that is both an effective treatment and also associated with minimal toxicity.
Approximately, 30% of new breast cancers diagnosed annually are among women older than 70 years of age. Age-adjusted trends note a relatively higher incidence of stage I breast cancer in women between the ages of 70-74 years. For this group of patients, it is imperative that we take a closer look at the evidence-base for our current practice standards, and evaluate opportunities to improve cancer care delivery in the elderly.
Randomized trials have helped arrive at an acceptance of adjuvant endocrine monotherapy in older patients with ER positive, node negative breast cancer. However, in the older patients high rates of non-compliance to tamoxifen secondary to poor tolerance is widely recognized. Emerging data also detail the side effect profile of aromatase inhibitors. Most commonly observed symptoms of arthralgia, reduced bone mineral density, and increased risk of fractures throughout the duration of treatment are important considerations for an older population. At least a quarter of patients on aromatase inhibitors discontinue therapy specifically due to skeletal events and musculoskeletal symptoms. Overall, the side effects of ET contribute to a high rate of non-compliance and negative impact on patients’ quality of life.
Author Interviews, Breast Cancer, Chemotherapy, NEJM / 27.03.2019
Gain in Survival with Fulvestrant plus Anastrozole in Metastatic Breast Cancer
MedicalResearch.com Interview with:
[caption id="attachment_48191" align="alignleft" width="150"] Dr. Mehta[/caption]
Rita Mehta, MD, HS Clinical Professor,
Chao Family Comprehensive Cancer Center
University of California School of Medicine, Irvine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Most patients with HR-positive breast cancer become resistant to hormonal therapies like aromatase inhibitor-anastrozole over time, and downregulating estrogen receptor was identified as a mechanism for overcoming or delaying resistance to hormonal therapy in advanced HR-positive breast cancer. The prospective, randomized phase III S0226 trial, first reported by us in NEJM 2012, showed that the selective estrogen receptor degrader fulvestrant in combination with anastrozole significantly improved progression-free survival in 707 women with HR-positive metastatic breast cancer in first-line setting.
Treatment with the selective estrogen receptor degrader (SERD) fulvestrant achieved a clinically significant and meaningful improvement in overall survival in patients with hormone receptor (HR)-positive advanced breast cancer in first-line therapy, according to the final analysis of overall survival results from the S0226 study reported by us (Mehta et al. NEJM 2019)
Dr. Mehta[/caption]
Rita Mehta, MD, HS Clinical Professor,
Chao Family Comprehensive Cancer Center
University of California School of Medicine, Irvine
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Most patients with HR-positive breast cancer become resistant to hormonal therapies like aromatase inhibitor-anastrozole over time, and downregulating estrogen receptor was identified as a mechanism for overcoming or delaying resistance to hormonal therapy in advanced HR-positive breast cancer. The prospective, randomized phase III S0226 trial, first reported by us in NEJM 2012, showed that the selective estrogen receptor degrader fulvestrant in combination with anastrozole significantly improved progression-free survival in 707 women with HR-positive metastatic breast cancer in first-line setting.
Treatment with the selective estrogen receptor degrader (SERD) fulvestrant achieved a clinically significant and meaningful improvement in overall survival in patients with hormone receptor (HR)-positive advanced breast cancer in first-line therapy, according to the final analysis of overall survival results from the S0226 study reported by us (Mehta et al. NEJM 2019)
- Results showed that median overall survival improved by 7.8 months with anastrozole plus fulvestrant (median overall survival = 49.8 months) compared to anastrozole (median overall survival = 42.0 months).
- The improvement was even greater in patients with endocrine naive disease, with an absolute improvement in median overall survival of 11.9 months.
- No new safety signals were observed with longer follow-up.
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Chemotherapy, NEJM / 24.02.2019
Antibody–Drug Conjugate in Refractory Metastatic Triple-Negative Breast Cancer
MedicalResearch.com Interview with:
[caption id="attachment_47551" align="alignleft" width="135"] Dr. Bardia[/caption]
Aditya Bardia, MBBS, MPH
Director, Precision Medicine, Center for Breast Cancer,
Attending Physician
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston, MA 02114
MedicalResearch.com: What is the background for this study?
Response: Metastatic triple negative breast cancer is associated with aggressive tumor biology, and tends to affect younger patients and African Amerians. The response rate with standard chemotherapy regimens in patients with pre-treated metastatic TNBC ranges from 10-15%, and median progression-free survival ranges from 3-4 months. The median survival of metastatic TNBC is around 12 months and has not changed in the past 20 years. Thus, treatment of metastatic triple negative breast cancer represents an unmet clinical need.
Dr. Bardia[/caption]
Aditya Bardia, MBBS, MPH
Director, Precision Medicine, Center for Breast Cancer,
Attending Physician
Massachusetts General Hospital Cancer Center
Harvard Medical School
Boston, MA 02114
MedicalResearch.com: What is the background for this study?
Response: Metastatic triple negative breast cancer is associated with aggressive tumor biology, and tends to affect younger patients and African Amerians. The response rate with standard chemotherapy regimens in patients with pre-treated metastatic TNBC ranges from 10-15%, and median progression-free survival ranges from 3-4 months. The median survival of metastatic TNBC is around 12 months and has not changed in the past 20 years. Thus, treatment of metastatic triple negative breast cancer represents an unmet clinical need.
Author Interviews, Chemotherapy, Colon Cancer / 12.01.2019
First Patient Dosed in Phase 3 AGENT Study for Metastatic Colorectal Cancer
MedicalResearch.com interview with:
[caption id="attachment_46915" align="alignleft" width="133"] Anders Rabbe[/caption]
Anders Rabbe
CEO of Isofol Medical
MedicalResearch.com: What is the background for this study? How common is colorectal cancer?
Response: Colorectal cancer (CRC) is one of the most common forms of cancer with more than 1.8 million new cases identified globally every year. Due to a lack of new therapeutic options and a high mortality rate, colorectal cancer is a disease with a significant unmet need for effective new treatments.
Isofol is developing arfolitixorin (Modufolin®) to improve the efficacy of standard of care chemotherapy for advanced colorectal cancer. Arfolitixorin is the company’s proprietary drug candidate currently being studied in a global Phase 3 AGENT study (ISO-CC-007) as a first-line treatment for patients with metastatic colorectal cancer (mCRC), which just enrolled its first patient in December of 2018.
Anders Rabbe[/caption]
Anders Rabbe
CEO of Isofol Medical
MedicalResearch.com: What is the background for this study? How common is colorectal cancer?
Response: Colorectal cancer (CRC) is one of the most common forms of cancer with more than 1.8 million new cases identified globally every year. Due to a lack of new therapeutic options and a high mortality rate, colorectal cancer is a disease with a significant unmet need for effective new treatments.
Isofol is developing arfolitixorin (Modufolin®) to improve the efficacy of standard of care chemotherapy for advanced colorectal cancer. Arfolitixorin is the company’s proprietary drug candidate currently being studied in a global Phase 3 AGENT study (ISO-CC-007) as a first-line treatment for patients with metastatic colorectal cancer (mCRC), which just enrolled its first patient in December of 2018.
Author Interviews, Cancer Research, Chemotherapy, Menopause, Mental Health Research / 02.01.2019
What Causes ‘Chemo Brain’ in Women?
MedicalResearch.com Interview with:
[caption id="attachment_46764" align="alignleft" width="128"] Dr. Gervais[/caption]
Nicole J. Gervais, Ph.D.
Postdoctoral fellow | Einstein lab
University of Toronto, Department of Psychology
Toronto, ON
MedicalResearch.com: What is the background for this study?
Response: Aromatase inhibitors (AIs) including letrozole are given as an adjuvant therapy for postmenopausal women with hormone receptor positive breast cancer. Women taking this drug have reported a number of symptoms including hot flashes, memory complaints and mood changes. However, not all studies report memory issues. This might be due to the fact that studies in this population are hampered by confounds, such as chemotherapy/radiotherapy, stress and disease stage, all of which can also adversely impact memory. These confounds make it challenging to observe the independent effects of AIs on memory. By using a non-human primate model, we were able to examine the effects of aromatase inhibition on these symptoms as well as brain function without these confounding effects.
Dr. Gervais[/caption]
Nicole J. Gervais, Ph.D.
Postdoctoral fellow | Einstein lab
University of Toronto, Department of Psychology
Toronto, ON
MedicalResearch.com: What is the background for this study?
Response: Aromatase inhibitors (AIs) including letrozole are given as an adjuvant therapy for postmenopausal women with hormone receptor positive breast cancer. Women taking this drug have reported a number of symptoms including hot flashes, memory complaints and mood changes. However, not all studies report memory issues. This might be due to the fact that studies in this population are hampered by confounds, such as chemotherapy/radiotherapy, stress and disease stage, all of which can also adversely impact memory. These confounds make it challenging to observe the independent effects of AIs on memory. By using a non-human primate model, we were able to examine the effects of aromatase inhibition on these symptoms as well as brain function without these confounding effects.
Author Interviews, Chemotherapy, JAMA, Prostate Cancer, Radiation Therapy, Surgical Research, UT Southwestern / 21.09.2018
Factor in Quality of Life When Deciding Radiotherapy vs Surgery in Patients With Oropharyngeal Cancer
MedicalResearch.com Interview with: [caption id="attachment_44703" align="alignleft" width="122"] Dr. Sher[/caption] Dr. David Sher MD MPH Radiation Oncology, Harold C. Simmons Comprehensive Cancer Center UTSouthwestern Medical Center Associate...
Author Interviews, Breast Cancer, Cancer Research, Chemotherapy, Radiation Therapy / 22.08.2018
Continued Aggressive Treatment Indicated For Younger Women with Breast Cancer Who Have Incomplete Response to Chemo
MedicalResearch.com Interview with:
[caption id="attachment_44079" align="alignleft" width="200"] Dr. Kathleen Horst[/caption]
Kathleen Horst, MD
Associate Professor of Radiation Oncology (Radiation Therapy)
Stanford University Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We were interested in focusing on young women with breast cancer as this is a high-risk patient population that is not studied on its own in clinical trials. Furthermore, the available data on treating breast cancer with neoadjuvant chemotherapy (NAC) does not include detailed outcomes for women under the age of 40 years.
Because most women who are diagnosed with breast cancer in this age group will have aggressive disease, most of them will be treated with NAC followed by surgery. From prospective randomized trials we know that women with breast cancer who attain a pathologic complete response (PCR) to neoadjuvant chemotherapy fare significantly better than those who do not. In addition, existing data suggest that a complete response in the lymph nodes also portends a better prognosis. This is the foundation for the currently ongoing NSABP B-51/RTOG 1304 trial, which is evaluating the role of nodal irradiation in those women who attain a pathologic complete response in the lymph nodes after NAC. We wanted to know whether differences in pathologic response in the breast versus lymph nodes led to different clinical outcomes in this patient group.
We evaluated outcomes following neoadjuvant chemotherapy for breast cancer in 155 women age 40 and younger. We focused on pathologic response in the breast and lymph nodes as predictors of disease recurrence and survival. We found that any residual disease in either the breast or lymph nodes lessened the chance of cure significantly.
Importantly, women who attained a complete response in the lymph nodes but continued to have residual disease in the breast fared just as poorly as those who remained lymph node positive following neoadjuvant chemotherapy.
Dr. Kathleen Horst[/caption]
Kathleen Horst, MD
Associate Professor of Radiation Oncology (Radiation Therapy)
Stanford University Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: We were interested in focusing on young women with breast cancer as this is a high-risk patient population that is not studied on its own in clinical trials. Furthermore, the available data on treating breast cancer with neoadjuvant chemotherapy (NAC) does not include detailed outcomes for women under the age of 40 years.
Because most women who are diagnosed with breast cancer in this age group will have aggressive disease, most of them will be treated with NAC followed by surgery. From prospective randomized trials we know that women with breast cancer who attain a pathologic complete response (PCR) to neoadjuvant chemotherapy fare significantly better than those who do not. In addition, existing data suggest that a complete response in the lymph nodes also portends a better prognosis. This is the foundation for the currently ongoing NSABP B-51/RTOG 1304 trial, which is evaluating the role of nodal irradiation in those women who attain a pathologic complete response in the lymph nodes after NAC. We wanted to know whether differences in pathologic response in the breast versus lymph nodes led to different clinical outcomes in this patient group.
We evaluated outcomes following neoadjuvant chemotherapy for breast cancer in 155 women age 40 and younger. We focused on pathologic response in the breast and lymph nodes as predictors of disease recurrence and survival. We found that any residual disease in either the breast or lymph nodes lessened the chance of cure significantly.
Importantly, women who attained a complete response in the lymph nodes but continued to have residual disease in the breast fared just as poorly as those who remained lymph node positive following neoadjuvant chemotherapy.
Author Interviews, Breast Cancer, Chemotherapy, JAMA / 05.06.2018
Everolimus Plus Exemestane vs Monotherapy for ER+ HER2- Advanced Breast Cancer
MedicalResearch.com Interview with:
[caption id="attachment_42177" align="alignleft" width="128"]
Dr. Jerusalem[/caption]
Dr. Guy Jerusalem, MD, PhD
CHU Sart Tilman Liege and Liege University
Liege, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted.
The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74).
A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design.
Dr. Jerusalem[/caption]
Dr. Guy Jerusalem, MD, PhD
CHU Sart Tilman Liege and Liege University
Liege, Belgium
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-6 was conducted to fulfill postapproval regulatory commitments to the FDA and EMA to estimate treatment benefit with EVE + EXE vs EVE alone or CAP for ER+, HER2− ABC that had progressed on an NSAI. Everolimus plus exemestane has not previously been compared with everolimus alone or capecitabine in a randomized setting.Data describing everolimus alone are limited to a single phase 2 study of just 19 patients. Thus, the FDA deemed it important to ascertain the efficacy of everolimus alone for ER+ breast cancer, and to determine the contribution of exemestane to combination therapy with everolimus. Capecitabine is often the first chemotherapeutic agent given for ER+ breast cancer that has progressed on anti-estrogen therapy. It has a reported PFS of 4.1–7.9 months among patients with HER2-negative advanced breast cancer. However, it has a different safety profile to everolimus or exemestane, and a comparison of endocrine-based combination therapy with single-agent chemotherapy was yet to be conducted.
The median PFS with EVE + EXE (8.4 months) was consistent with BOLERO-2 (7.8 months), and compared to EVE alone here (6.8 months) corresponded to an estimated 26% reduction of risk of disease progression or death (HR 0.74).
A numerical median PFS difference was observed for CAP over EVE + EXE (9.6 vs 8.4 months), which may be attributed to various baseline characteristics favoring CAP and potential informative censoring. The median PFS with capacitabine was longer than expected based on previous trials. Interpretation of the results of BOLERO-6 must consider the limited sample size and open-label design.
Author Interviews, Cancer Research, Chemotherapy, Erectile Dysfunction / 18.04.2018
Erectile Dysfunction Drugs May Boost Effects of Chemotherapy
MedicalResearch.com Interview with:
[caption id="attachment_41214" align="alignleft" width="143"]
Dr Pan Pantziarka[/caption]
Dr Pan Pantziarka, PhD
Program Director, Drug Repurposing: Anticancer Fund
Coordinator: Repurposing Drugs in Oncology
(www.redo-project.org)
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Repurposing Drugs in Oncology (ReDO) project is an on-going collaboration assessing the evidence of anticancer activity in a wide range of already licensed non-cancer drugs. A subset of these drugs have a sufficient level of evidence to support clinical investigation and these are profiled in detail in order to synthesise the existing evidence and to bring it to the attention of clinical researchers.
In the case of the PDE5 inhibitors sildenafil, tadalafil and vardenafil the evidence is clear that these drugs have multiple anticancer mechanisms of action at clinically relevant dosing. In particular there is evidence that these drugs target anti-tumour immune responses, as shown from a small number of early stage clinical trials. This opens up the prospect of using these cheap and widely available drugs in combination with existing therapies to improve the number and duration of responses. The chance to increase the therapeutic effectiveness of immune checkpoint inhibitors is especially compelling and definitely warrants clinical research.
Dr Pan Pantziarka[/caption]
Dr Pan Pantziarka, PhD
Program Director, Drug Repurposing: Anticancer Fund
Coordinator: Repurposing Drugs in Oncology
(www.redo-project.org)
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: The Repurposing Drugs in Oncology (ReDO) project is an on-going collaboration assessing the evidence of anticancer activity in a wide range of already licensed non-cancer drugs. A subset of these drugs have a sufficient level of evidence to support clinical investigation and these are profiled in detail in order to synthesise the existing evidence and to bring it to the attention of clinical researchers.
In the case of the PDE5 inhibitors sildenafil, tadalafil and vardenafil the evidence is clear that these drugs have multiple anticancer mechanisms of action at clinically relevant dosing. In particular there is evidence that these drugs target anti-tumour immune responses, as shown from a small number of early stage clinical trials. This opens up the prospect of using these cheap and widely available drugs in combination with existing therapies to improve the number and duration of responses. The chance to increase the therapeutic effectiveness of immune checkpoint inhibitors is especially compelling and definitely warrants clinical research.
Author Interviews, Breast Cancer, Chemotherapy, JAMA, Novartis / 26.03.2018
Everolimus plus Endocrine Therapy: Effective 1st Line Option for Postmenopausal Women with HR+/HER2- Advanced Breast Cancer
MedicalResearch.com Interview with:
[caption id="attachment_40799" align="alignleft" width="145"]
Dr. Royce[/caption]
Melanie E. Royce, MD, PhD
Division of Hematology/Oncology
University of New Mexico Comprehensive Cancer Center
Albuquerque
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.
A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%).
Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression.
Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5).
Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted.
Dr. Royce[/caption]
Melanie E. Royce, MD, PhD
Division of Hematology/Oncology
University of New Mexico Comprehensive Cancer Center
Albuquerque
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: BOLERO-4 is an open label, single-arm, Phase II study that evaluates the combination of everolimus plus letrozole as a first-line treatment for hormone receptor (HR)-positive/human epidermal growth factor receptor (HER2)-negative advanced breast cancer patients, as well as the use of everolimus plus exemestane beyond initial progression. Results of the BOLERO-4 trial published in JAMA Oncology showed that everolimus in combination with endocrine therapy is an effective first-line treatment option for postmenopausal women with HR+/HER2- advanced breast cancer.
A total of 202 patients received everolimus in combination with letrozole as first-line treatment between March 7, 2013 and December 17, 2014. Median progression-free survival (PFS) in the first-line setting was 22.0 months (95% CI 18.1-25.1) with an overall response rate of 45% (95% CI 38.1-52.2) and clinical benefit rate of 74% (95% CI 67.7-80.1). A total of 152 (75%) discontinued treatment, primarily due to disease progression (51%) or adverse events (16%).
Data from a smaller number of patients in BOLERO-4 also show limited efficacy with continued everolimus, combined with exemestane, following disease progression.
Second-line treatment was ongoing in 16 (32%) patients, while 34 (68%) had discontinued. The most frequent reason for second-line treatment discontinuation was disease progression (56%). In the second-line setting, median PFS was 3.7 months (95% CI 1.9-7.4) with an overall response of 6% (95% CI 1.3-16.5) and clinical benefit rate of 28% (95% CI 16.2-42.5).
Safety findings from BOLERO-4 are consistent with previous studies of Afinitor in advanced breast cancer. The most common (≥ 20% incidence) first-line all-grade adverse events were stomatitis (69%), weight loss (44%), nausea (37%) and anemia (35%). Most were ‘low grade’ in severity (grade 1 or 2) and generally well managed. Safety findings show the most common (≥ 10% incidence) second-line adverse events were stomatitis (20%) and weight loss (20%). Lower rates of stomatitis in second-line were noted.
Author Interviews, Cancer Research, Chemotherapy, Journal Clinical Oncology / 06.02.2018
ASPIRE: Combination Therapy With KYPROLIS (carfilzomib) Extended Overall Survival in Relapsed/Refractory Multiple Myeloma
MedicalResearch.com Interview with:
[caption id="attachment_39858" align="alignleft" width="200"]
Dr. Siegel[/caption]
David S. Siegel, MD, PhD
Chief, Myeloma Division
John Theurer Cancer Center
Hackensack University Medical Center
Hackensack, NJ 07601
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Siegel[/caption]
David S. Siegel, MD, PhD
Chief, Myeloma Division
John Theurer Cancer Center
Hackensack University Medical Center
Hackensack, NJ 07601
MedicalResearch.com: What is the background for this study? What are the main findings?
- We reported results from the prospectively planned final analysis of overall survival (OS) from the Phase 3 ASPIRE trial, an international, randomized study evaluating KYPROLIS (carfilzomib) in combination with lenalidomide and dexamethasone (KRd) versus lenalidomide and dexamethasone alone (Rd) in patients with relapsed or refractory multiple myeloma following treatment with one to three prior regimens. Overall survival was a secondary endpoint in the trial.
- Data published last week in the Journal of Clinical Oncology demonstrated that the addition of KYPROLIS to Rd reduced the risk of death by 21 percent versus Rd alone and extended OS by 7.9 months (median OS 48.3 months for KRd versus 40.4 months for Rd, HR = 0.79, 95 percent CI, 0.67 – 0.95; one-sided p=0.0045).
- Notably, an OS improvement of 11.4 months was observed for patients at first relapse (47.3 versus 35.9 months [HR = 0.81, 95 percent CI, 0.62 – 1.06]), supporting early use of KRd.
- The safety data from ASPIRE was consistent with the known safety profile of KYPROLIS. The most common adverse events (greater than or equal to 20 percent) in the KYPROLIS arm were diarrhea, anemia, neutropenia, fatigue, upper respiratory tract infection, pyrexia, cough, hypokalemia, thrombocytopenia, muscle spasms, pneumonia, nasopharyngitis, nausea, constipation, insomnia and bronchitis.
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Chemotherapy / 22.01.2018
Repurposed Drug Hydroxyurea May Improve Glioblastoma’s Response to Chemotherapy
MedicalResearch.com Interview with:
[caption id="attachment_39476" align="alignleft" width="149"]
Dr. Tannous[/caption]
Bakhos Tannous, PhD
Neuro-Oncology Division
Department of Neurology
MGH
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ.
We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models.
Dr. Tannous[/caption]
Bakhos Tannous, PhD
Neuro-Oncology Division
Department of Neurology
MGH
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Glioblastoma (GBM) is the most common and most aggressive type of brain tumors in adults. Over the last two decades, the major improvement in the treatment for GBM has been the addition of the chemotherapeutic temozolomide (TMZ) to the standard of care (surgery and radiation), however, despite this aggressive therapy, over 90% of patients die within five years after diagnosis. Further, only about half of GBM patients really benefit from TMZ treatment, while the other half are somewhat resistant to TMZ since their tumor endogenously carry a DNA repair mechanism that removes DNA adducts caused by TMZ.
We therefore wanted to find a combination therapy that overcomes TMZ resistance and works in all GBM patient populations, with a fast transition to the clinic. Through a repurposing drug screening aiming at recycling of old known drugs for new therapies, we found that the FDA-approved drug hydroxyurea to synergizes with temozolomide in patient-derived GBM cells from newly diagnosed and recurrent tumors, irrespective of their DNA repair mechanism. The combination of hydroxyurea and TMZ worked very well in all different patient cell population tested, and was not specific to one subtype, and lead to a significant increase in survival rate in different mouse models.
Author Interviews, Chemotherapy, JAMA, Ovarian Cancer / 26.12.2017
Ovarian Cancer Trial: Disappointing Results of Paclitaxel With/Without Pazopanib
MedicalResearch.com Interview with:
Debra Richardson, MD, FACOG, FACS
Associate Professor, Section of Gynecologic Oncology,
Oklahoma TSET Phase I Program
Stephensen Cancer Center
The University of Oklahoma
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ovarian cancer is the leading cause of gynecologic cancer deaths. Pazopanib is an oral multitarget tyrosine kinase inhibitor of VEGF receptors 1, 2, and 3; platelet-derived growth factor (PDGF) receptors α and β and c-KIT. Weekly paclitaxel is an active agent for recurrent ovarian cancer.
This was a national, randomized, double-blind, placebo controlled phase 2b trial of weekly paclitaxel with or without pazopanib for the treatment of recurrent ovarian cancer. The primary objective was to estimate the progression-free survival (PFS) hazard ratio (HR) of the combination of weekly paclitaxel (80mg/m2 D1, 8, 15 every 28 days) and pazopanib (800mg PO daily) compared with weekly paclitaxel and placebo in women with persistent or recurrent ovarian cancer. 106 women were enrolled. There was no difference in median PFS, overall survival (OS), or proportion responding. Severe hypertension was more common on the pazopanib plus paclitaxel arm. More patients discontinued treatment on the paclitaxel arm for disease progression, and more on the pazopanib plus paclitaxel arm for adverse events. Patients with VEGFA CC genotype may be more resistant to weekly paclitaxel than those with the AC or AA genotype.
Author Interviews, Cancer Research, Chemotherapy, Diabetes, PLoS / 08.12.2017
Older Diabetes Drug Metformin May Resensitize Tumors to Chemotherapy
MedicalResearch.com Interview with:
[caption id="attachment_38714" align="alignleft" width="200"]
Dr. Arnason[/caption]
Terra G Arnason, MD PhD, Associate Professor,
Division of Endocrinology,
Department of Medicine
University of Saskatchewan
Saskatoon, SK, Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Response: Metformin has been used worldwide for decades to treat Type diabetes.
Metformin is a cheap non-toxic compound that was originally plant derived. In the past decade a number of meta-analyses have demonstrated that Type 2 individuals taking
metformin have a reduced risk of developing many different cancers and do better
longterm. The molecular events facilitating metformin’s activity remain obscure and
it is unknown whether metformin can help cancer patients avoid the development of
drug resistant cancers years after successful treatment.
In our study we asked whether metformin can not only restore sensitivity of multiple drug resistant tumors to chemotherapy once again, but whether metformin can prevent the development of multiple drug resistance in the "rst place. We demonstrate that metformin can sensitize drug resistant cells to chemotherapy once again, which supports recent
studies, but we also show for the "first time that Metformin can prevent the
progression of cancer cells towards drug resistance using cell culture experiments.
Dr. Arnason[/caption]
Terra G Arnason, MD PhD, Associate Professor,
Division of Endocrinology,
Department of Medicine
University of Saskatchewan
Saskatoon, SK, Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Response: Metformin has been used worldwide for decades to treat Type diabetes.
Metformin is a cheap non-toxic compound that was originally plant derived. In the past decade a number of meta-analyses have demonstrated that Type 2 individuals taking
metformin have a reduced risk of developing many different cancers and do better
longterm. The molecular events facilitating metformin’s activity remain obscure and
it is unknown whether metformin can help cancer patients avoid the development of
drug resistant cancers years after successful treatment.
In our study we asked whether metformin can not only restore sensitivity of multiple drug resistant tumors to chemotherapy once again, but whether metformin can prevent the development of multiple drug resistance in the "rst place. We demonstrate that metformin can sensitize drug resistant cells to chemotherapy once again, which supports recent
studies, but we also show for the "first time that Metformin can prevent the
progression of cancer cells towards drug resistance using cell culture experiments.
Author Interviews, Chemotherapy, Lung Cancer, Science / 24.07.2017
Small Cell Lung Cancers Form Chemotherapy-Resistant Circulating Tumor Spheres
MedicalResearch.com Interview with:
[caption id="attachment_36074" align="alignleft" width="133"]
Prof. Hamilton[/caption]
Prof. Gerhard Hamilton
Department of Obstetrics and Gynecology
Medical University of Vienna
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the
low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness.
Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs - if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.
Prof. Hamilton[/caption]
Prof. Gerhard Hamilton
Department of Obstetrics and Gynecology
Medical University of Vienna
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Small cell lung cancer (SCLC) is a highly aggressive tumor (15 % of all lung cancers) mainly of patients with high tobacco consumption which shows an extremely poor survival (< 5% 2-year survival rate). Unfortunately the
low survival rates of advanced SCLC cases has not improved significantly during the last decades, with platinum drugs/etoposide and topotecan employed for first- and second-line chemotherapy, respectively. All kinds of new chemotherapeutics, targeted drugs and immunotherapies either failed or resulted in prolongation of survival of several months at best. SCLC responds well to first-line therapy but relapses within a short time as chemoradioresistant tumor. The failure of hundreds of registered studies seem to be linked to the lack of knowledge of the mechanism of resistance of SCLCs and proper ways to reverse the refractoriness.
Small cell lung cancer is distinguished by excessive numbers of circulating tumor cells (CTCs) in advanced stages. CTCs contain the founder of metastasis and seem to constitute a highly chemoresistant cell population. Thus, we ware able to establish a panel of permanent CTC lines in vitro for the first time (8 SCLC lines so far from blood samples). Although CTCs were considered to be chemoresistant we detected that they are chemosensitive in vitro in form of single cell suspensions. However, all CTC lines developed spontaneously into large multicellular aggregates, termed tumorospheres, which grow up to 1-2 mm in size and exhibit high chemoradioresistance due to limited drug perfusion as well as content of quiescent and hypoxic cells. Resistance to irradiation seems to be caused by lack of oxygen, such limiting the generation of oxygen radicals. High resistance mediated by the occurrence of tumorospheres easily explains the failure of a large number of drugs - if one is not able to achieve a sufficient concentration of a drug in cancer cells and the cells are quiescent, the respective compounds will not be able to destroy the target cells, regardless of their chemical nature.
Author Interviews, Breast Cancer, Chemotherapy, JAMA, MD Anderson, Surgical Research / 20.04.2017
Some Breast Cancer Patients With Complete Response To Neoadjuvant Therapy Can Avoid Further Surgery
MedicalResearch.com Interview with:
[caption id="attachment_33987" align="alignleft" width="136"]
Dr. Tadros[/caption]
Audree Tadros, MD, MPH
Chief Administrative Fellow, Breast Surgical Oncology Training Program
Department of Breast Surgical Oncology
MD Anderson Cancer Center and
[caption id="attachment_33988" align="alignleft" width="120"]
Dr. Kuerer[/caption]
Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Cancer Research
Dept of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program
MedicalResearch.com: What is the background for this study?
Response: Neoadjuvant chemotherapy (NCT) has the ability to confer a pCR (pathologic complete response-when no residual cancer is found) in both the breast and axillary lymph nodes. We know that this is most likely to occur in women with HER2 positive and triple negative disease. The high rate of pCR among these patients raises the question of whether surgery is still required, particularly among those who will receive adjuvant radiation therapy.
Until recently, we lacked the ability to pre-operatively predict patients who achieved a breast pCR. Recently, we completed a clinical feasibility trial examining the ability of image-guided biopsy to predict a pCR after neoadjuvant chemotherapy. Our biopsy technique was able to accurately predict a pCR in 98% of patients with only a 5% false negative rate. Based upon these findings, we believe we can accurately determine which patients achieve a breast pCR. This led us to develop a clinical trial to see if breast surgery is redundant in patients who achieve a pCR. An important question that remained was if we are going to omit breast surgery in these exceptional responders, can we also omit axillary surgery?
Dr. Tadros[/caption]
Audree Tadros, MD, MPH
Chief Administrative Fellow, Breast Surgical Oncology Training Program
Department of Breast Surgical Oncology
MD Anderson Cancer Center and
[caption id="attachment_33988" align="alignleft" width="120"] Dr. Kuerer[/caption]
Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Cancer Research
Dept of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program
MedicalResearch.com: What is the background for this study?
Response: Neoadjuvant chemotherapy (NCT) has the ability to confer a pCR (pathologic complete response-when no residual cancer is found) in both the breast and axillary lymph nodes. We know that this is most likely to occur in women with HER2 positive and triple negative disease. The high rate of pCR among these patients raises the question of whether surgery is still required, particularly among those who will receive adjuvant radiation therapy.
Until recently, we lacked the ability to pre-operatively predict patients who achieved a breast pCR. Recently, we completed a clinical feasibility trial examining the ability of image-guided biopsy to predict a pCR after neoadjuvant chemotherapy. Our biopsy technique was able to accurately predict a pCR in 98% of patients with only a 5% false negative rate. Based upon these findings, we believe we can accurately determine which patients achieve a breast pCR. This led us to develop a clinical trial to see if breast surgery is redundant in patients who achieve a pCR. An important question that remained was if we are going to omit breast surgery in these exceptional responders, can we also omit axillary surgery?
Author Interviews, Breast Cancer, Chemotherapy, Personalized Medicine / 24.02.2017
Precision Therapy In Early Stages For Triple Negative Breast Cancer
MedicalResearch.com Interview with:
Eran Andrechek, PhD
Associate Professor
Department of Physiology
Michigan State University
East Lansing, MI
MedicalResearch.com: What is the background for this study?
Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment. Other types can be treated with personalized medicine, resulting in better outcome. For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself. The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy.
The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options. Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer.
Associate Professor
Department of Physiology
Michigan State University
East Lansing, MI
MedicalResearch.com: What is the background for this study?
Response: Of the various types of breast cancer, triple negative breast cancer (lacking estrogen receptor, progesterone receptor and HER2) has the worst outcome and is largely limited to chemotherapy for treatment. Other types can be treated with personalized medicine, resulting in better outcome. For instance, a HER2+ve breast cancer can be treated with Herceptin, which targets HER2 itself. The fact that triple negative breast cancer lacks these sort of targeted treatments presents a clear need in breast cancer therapy.
The goal of this study was to bring together our computational work using large databases from breast cancer with research into therapeutic options. Essentially we wanted to ask if we could use patterns in what genes were being expressed to predict optimal therapy for triple negative breast cancer.
Author Interviews, Breast Cancer, Cancer, Chemotherapy, Race/Ethnic Diversity / 16.02.2017
For African American Women, Breast Cancer Symptoms Worsen During Initial Treatments
MedicalResearch.com Interview with::
[caption id="attachment_32079" align="alignleft" width="160"]
Margaret Rosenzweig[/caption]
Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN
Acute and Tertiary Care Department
University of Pittsburgh School of Nursing
MedicalResearch.com: What is the background for this study?
Response: A significant survival disparity still exists between African American and non-Hispanic white women diagnosed with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The current study was a secondary, exploratory aim from the Attitudes, Communication, Treatment, and Support (ACTS) Intervention to Reduce Breast Cancer Treatment Disparity study, which is a randomized controlled trial of a psychoeducational intervention to encourage acceptance and adherence to chemotherapy compared with usual care for African American women with breast cancer. The purpose of the current study was to:
1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and
2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe.
Margaret Rosenzweig[/caption]
Margaret Q. Rosenzweig PhD, CRNP-C, AOCNP, FAAN
Acute and Tertiary Care Department
University of Pittsburgh School of Nursing
MedicalResearch.com: What is the background for this study?
Response: A significant survival disparity still exists between African American and non-Hispanic white women diagnosed with breast cancer. There is evidence that symptom incidence, associated distress, and overall cancer-related distress may be unexplored, important contributing factors. The current study was a secondary, exploratory aim from the Attitudes, Communication, Treatment, and Support (ACTS) Intervention to Reduce Breast Cancer Treatment Disparity study, which is a randomized controlled trial of a psychoeducational intervention to encourage acceptance and adherence to chemotherapy compared with usual care for African American women with breast cancer. The purpose of the current study was to:
1) describe and compare the number of chemotherapy-related symptoms and associated distress among AA women with breast cancer over the course of chemotherapy at 3 time points (at baseline before initiating chemotherapy, midpoint, and at the completion of chemotherapy); and
2) to describe the relationship between the number of chemotherapy-related symptoms and overall cancer distress compared with the ability to receive at least 85% of the prescribed chemotherapy within the prescribed timeframe.
AACR, Author Interviews, Biomarkers, Breast Cancer, Chemotherapy / 26.12.2016
ER-beta May Identify Breast Cancer Patients For Whom Chemotherapy is Sufficient
MedicalResearch.com Interview with:
Helena Jernström, PhD
Associate Professor in Experimental Oncology
Study Coordinator for Graduate studies Division of Oncology and Pathology
Coordinator of the programmes in statistics and epidemiology for doctoral students at the Medical Faculty, Lund University
Division of Oncology and Pathology, Department of Clinical Sciences, Lund
Lund University Cancer Center/Kamprad
Lund, Sweden
MedicalResearch.com: What is the background for this study?
Response: There is a need for better predictive markers to guide selection of therapy in breast cancer patients. Estrogen receptor beta (ER-beta) may confer prognostic information beyond what is currently obtained by the established clinical markers, including ER-alpha, which is routinely evaluated.
Author Interviews, Breast Cancer, Chemotherapy, Mammograms, MD Anderson, Surgical Research / 12.12.2016
Image-Guided Biopsies May Reduce Need For Surgery in Breast Cancer Patients Who Respond to Chemotherapy
MedicalResearch.com Interview with:
[caption id="attachment_30458" align="alignleft" width="175"]
Dr. Henry M. Kuerer[/caption]
Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Network Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Research
Department of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program
MedicalResearch.com: What is the background for this study?
Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation.
We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed?
The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not.
Dr. Henry M. Kuerer[/caption]
Henry M. Kuerer, MD, PhD, FACS
Executive Director, Breast Network Programs
MD Anderson Cancer Network
PH and Fay Etta Robinson Distinguished Professor in Research
Department of Breast Surgical Oncology
Director, Breast Surgical Oncology Training Program
MedicalResearch.com: What is the background for this study?
Response: Worldwide, triple negative and HER2 positive breast cancers, combined, account for about 370,000 women diagnosed annually. With recent advances in neoadjuvant systemic therapy (NST, chemotherapy and targeted therapy given before surgery) for both subsets, the pCR (pathologic complete response- when no residual cancer is found) rates found at the time of surgery in these populations can be as high as 60 percent. This high rate of pCR naturally raises the question of whether surgery is required for all patients, particularly those who will receive adjuvant radiation.
We believe surgery may potentially be redundant – at least for these two subtypes of breast cancer – because of such a high chance for no evidence of disease at the time of pathological review. If there’s no cancer left after the patient has received chemotherapy and the patient is going to receive local radiation therapy, is surgery actually needed?
The challenge has been that standard breast imaging methods cannot accurately predict residual disease after NST. However, by doing the same image-guided percutaneous needle biopsies after neoadjuvant systemic therapy that we do at time of diagnosis, our preliminary research reveals that we may be able to accurately predict which women will have cancer or not.
Author Interviews, Breast Cancer, Chemotherapy, Genetic Research / 11.12.2016
Breast Cancer: 21-gene assay Can Help Choose Neoadjuvant Therapy
MedicalResearch.com Interview with: [caption id="attachment_30440" align="alignleft" width="133"] Dr. Harry Bear[/caption] Harry D. Bear, MD, PhD Walter Lawrence, Jr. Distinguished Professor of Oncology; Chair, Division...
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 09.12.2016
Breast Cancer: PARP Inhibitor Veliparib Has Potential To Enhance Platinum Chemotherapy in Recurrent or Metastatic Disease
MedicalResearch.com Interview with:
Vince Giranda, M.D., PH.D.
Project Director
AbbVie Oncology Development
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: In this Phase 2 study, called BROCADE 2, veliparib combined with the platinum chemotherapy regimen carboplatin and paclitaxel showed positive trends in overall survival (OS) and progression-free survival (PFS), although these were not statistically significant. Importantly there were no meaningful increase in side effects with the addition of veliparib to carboplatin and paclitaxel. The veliparib combination regimen also demonstrated a significantly higher objective response rate.
Author Interviews, Cancer Research, Chemotherapy / 27.11.2016
Low-Dose Regularly Timed Chemotherapy May Keep Some Resistant Cancers in Check
MedicalResearch.com Interview with:
[caption id="attachment_29986" align="alignleft" width="150"]
Dr. Kelvin K. Tsai[/caption]
Kelvin K. Tsai, MD, PhD
Associate Investigator and Attending Physician
Laboratories for Tumor Aggressiveness and Stemness
National Institute of Cancer Research, National Health Research Institutes
Associate Professor and Principal Investigator
Laboratories of Advanced Molecular Therapeutics
Graduate Institute of Clinical Medicine
College of Medicine, Taipei Medical University, Taiwan
MedicalResearch.com: What is the background for this study?
Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers.
We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated.
Dr. Kelvin K. Tsai[/caption]
Kelvin K. Tsai, MD, PhD
Associate Investigator and Attending Physician
Laboratories for Tumor Aggressiveness and Stemness
National Institute of Cancer Research, National Health Research Institutes
Associate Professor and Principal Investigator
Laboratories of Advanced Molecular Therapeutics
Graduate Institute of Clinical Medicine
College of Medicine, Taipei Medical University, Taiwan
MedicalResearch.com: What is the background for this study?
Response: Human cancer is a complex organ consisting of a heterogenous collection of cancer cells and stroma cells. Many solid tumors such as breast cancer and pancreatic cancer are characterized by a pronounced stromal fibrosis termed desmoplasia. Studies showed that systemic chemotherapy can target not only cancer cells but also the stromal fibroblasts, which may have significant impacts on the treatment response in desmoplastic cancers.
We set out to study whether and how traditional “maximum tolerated dose (MTD)” chemotherapy affects the tumor fibroblasts and thereby modulates the treatment response, and if so how this therapy-induced stroma perturbation can be avoided or attenuated.
Author Interviews, Breast Cancer, Chemotherapy, Immunotherapy / 19.11.2016
MARIANNE Study of HER2+ Metastatic Breast Cancer: Trastuzumab Emtansine With or Without Pertuzumab vs Trastuzumab Plus Taxane
MedicalResearch.com Interview with:
[caption id="attachment_29794" align="alignleft" width="200"]
Dr. Edith Perez[/caption]
Edith Perez, MD
Vice President and Head of U.S. Medical Affairs
Genentech BioOncology
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy.
Dr. Edith Perez[/caption]
Edith Perez, MD
Vice President and Head of U.S. Medical Affairs
Genentech BioOncology
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: MARIANNE was designed to evaluate three HER2-targeted regimens in previously untreated (first-line) HER2-positive metastatic breast cancer (Kadcyla alone, Kadcyla plus Perjeta, Herceptin plus chemotherapy). The study met its non-inferiority endpoint, showing similar progression-free survival (PFS) among the three treatment arms. However, neither Kadcyla-containing treatment arm significantly improved PFS compared to Herceptin and chemotherapy.