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Kim Margolin, MD
KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified) )| Communities: Melanoma (Cutaneous) , Kidney and Renal Cancer | Answers: 8 |
| Member Since: Jul. 2012 |
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Professional Statement
Kim A. Margolin, MD, is Professor of Medicine at the University of Washington in Seattle and a member of the Division of Clinical Research at the Fred Hutchinson Cancer Research Center.
Dr. Margolin’s clinical efforts are in the treatment of melanoma, kidney cancer and germ cell cancer, and she is particularly interested in clinical trials that provide the newest investigational therapies for her patients. Melanoma and kidney cancer are often treated with immunotherapy, including vaccines, cytokines and immune-cell infusions. Germ cell cancer can be treated effectively with surgery and chemotherapy in most cases, and Dr. Margolin works closely with a multidisciplinary group in this area.
Dr. Margolin served a five-year term on the FDA’s Oncology Advisory Committee, “the most wonderful honor I have experienced in my career,” she says. She was also part of the American Board of Internal Medicine Oncology Committee where she wrote and developed questions for medical board exam candidates. In 2010, Margolin chaired the Cancer Education Committee for the American Society of Clinical Oncology.
Dr. Margolin received her MD from Stanford University, Stanford, CA. She completed her Internal Medicine Residency at Yale New Haven Hospital. She was a Post-Doctoral Fellow in Hematology/Oncology at University of California, San Diego. She was a Post-Doctoral Fellow in Hematology and Bone Marrow Transplantation at City of Hope National Medical Center, Duarte, CA.
Dr. Margolin’s clinical efforts are in the treatment of melanoma, kidney cancer and germ cell cancer, and she is particularly interested in clinical trials that provide the newest investigational therapies for her patients. Melanoma and kidney cancer are often treated with immunotherapy, including vaccines, cytokines and immune-cell infusions. Germ cell cancer can be treated effectively with surgery and chemotherapy in most cases, and Dr. Margolin works closely with a multidisciplinary group in this area.
Dr. Margolin served a five-year term on the FDA’s Oncology Advisory Committee, “the most wonderful honor I have experienced in my career,” she says. She was also part of the American Board of Internal Medicine Oncology Committee where she wrote and developed questions for medical board exam candidates. In 2010, Margolin chaired the Cancer Education Committee for the American Society of Clinical Oncology.
Dr. Margolin received her MD from Stanford University, Stanford, CA. She completed her Internal Medicine Residency at Yale New Haven Hospital. She was a Post-Doctoral Fellow in Hematology/Oncology at University of California, San Diego. She was a Post-Doctoral Fellow in Hematology and Bone Marrow Transplantation at City of Hope National Medical Center, Duarte, CA.
Professional Info
Credential: MD
Primary specialty: Oncology - Hematology/Oncology
Medical school: Stanford University School of Medicine
Residency: Yale New Haven Hospital
Fellowship: University of California, San Diego School of Medicine
Areas of expertise: Melanoma, kidney cancer, and germ cell cancer
Hospital affiliation: Seattle Cancer Care Alliance
Practice address:
1354 Aloha St.
Seattle, WA
98109
Practice phone number: (800) 804-8824
KimMargolinMD Activities
This is a very difficult question, because it is still under very intense investigation. There is no targeted therapy proven effective for patients with BRAF-mutated melanoma that is no longer responding to vemurafenib, although the recent discoveries of a large number of molecular mechanisms for resistance are leading to some new drug approaches that will be tested soon. Patients who have not previously received ipilimumab and who have relatively slow-growing melanoma may benefit from that drug or from entering clinical trials that contain that drug in a novel combination or sequence. Patients on vemurafenib who have limited growth in some but not all sites of metastasis may benefit from adding radiotherapy to the growing tumor while staying on vemurafenib, while others may respond to classical chemotherapy added to vemurafenib, but in both of these cases it will be necessary to complete ongoing clinical trials to assess the overall safety and effectiveness of these novel approaches.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
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9 months ago
The presence or absence of the BRAF v600 mutation and the apparent extent of disease and rate of growth are important deciding factors, together with the overall condition of the patient, other medical problems and other medications needed by the patient. Access to specialized centers for interleukin-2-based therapies or clinical trials with novel immunotherapies, drugs or combination therapies may also contribute to decision-making.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
Mutated c-kit is a “driver” molecular alteration in a very small percentage of melanomas, especially when they arise in the mucous membranes or the skin of the hands and feet. There are several approved drugs for other malignancies that block the cellular pathways coming from the mutated, activated c-kit protein (a receptor for a growth factor that, when mutated, causes the cells to grow faster and more independently of external signals). These drugs are being used for patients with melanoma who have the mutation, but the number of such patients is small, so the effectiveness of each drug remains under investigation.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
Cytokines are substances that mediate communication between cells, in particular those of the immune system that require very specific types of cytokine to function correctly. It is possible to administer large amounts of purified cytokines to patients with melanoma and to activate a large number of T- and related other lymphocytes that possess sufficient anti-melanoma activity to provide remission. Interferon is such a cytokine, although its activity is very modest in both advanced melanoma and in the adjuvant setting. Interleukin-2 is a cytokine approved for advanced melanoma that can provide remissions in about one-fifth of patients, some of which are longlasting and may be cures. Cytokines are also important for more complex therapies under investigation, such as T cells expanded outside of the body and then re-infused, followed by cytokines to stimulate the cells’ activity and numbers. Cytokines may also be important as part of cancer vaccines under investigation.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
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Answer |
9 months ago
There is no proven beneficial systemic therapy for patients with stage II melanoma. Many laboratories and clinical investigators are working on various forms of immunotherapy that may be safe and effective in higher-risk stages and could then be moved into the stage II arena. Immunotherapies will probably be the most important adjuvant therapies, as they are likely to have a favorable therapeutic index, defined as the relative risk (side effects and toxicities) versus benefit (enhancing the time free of relapse and possibly enhancing survival). Among the immunotherapies likely to be effective and safe in Stage 2 melanoma will be vaccines and related treatments that can be given safely to large groups of patients for long periods of time. If effective, some of these strategies may even find a place in prevention of new melanomas in individuals at high risk.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
1
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9 months ago
The main difference is that high-dose interferon is traditionally given with a 1-month induction period consisting of daily x 5/week intravenous infusions of the drug, followed by three-times-weekly self-administered injections under the skin for the ensuing 11 months. PEG-interferon is given as the weekly subcutaneous injections throughout the therapeutic period, which is intended to last for 5 years but may conclude earlier in the event of relapse or intolerance. The side effects of high-dose interferon are more severe during the induction period, when it is given in very high doses intravenously, and more tolerable during the period of thrice weekly injections under the skin. PEG-interferon is started at an initial moderate dose that is continued weekly for 8 weeks and followed by the maintenance dose, half as much as the induction dose, for the remainder of the 5 years of planned therapy. During the long-term treatment, side effects are comparable, in part because the dose of regular interferon may be lowered to manage side effects and keep them tolerable. The ability to reduce the chance of relapse is similar; in terms of enhancing survival, regular interferon has shown modest improvements in the overall patient groups, possibly more in some subgroups than others, while PEG-interferon has no overall impact on survival but has distinct benefits in well-defined subgroups which are currently being studied in greater detail (microscopic involvement of lymph node and ulceration of the primary melanoma).
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
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9 months ago
Depending on whether the site of this visit is in an academic or a private setting, the patient will be assessed for therapies with either a clinical trial (always the superior option for this disease, especially for first-line therapy) or with standard, approved therapies that depend on several features of the case. Staging of the melanoma to find all possible sites of involvement, including the brain, will be completed if not previously done. Mutational analysis, at the very least for BRAF mutation which determines the possibility of using vemurafenib at some point, will be obtained or reviewed if already performed. Other mutations can be looked for but may not have an active therapy until more drugs have been studied and approved in melanoma. After a thorough history and physical examination followed by a full review of laboratory results, radiographic and pathologic data, the oncologist will come up with a recommendation for therapy and discuss it with the patient and family, making sure to provide a good rationale for any recommended therapy and allow ample time for questions from the patient and all of the patient’s caregivers.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
1
Answer |
9 months ago
Anti-PD-1 antibody is a new fully human monoclonal antibody that targets the programmed-death receptor on activated cytotoxic T lymphocytes, blocking its interaction with the ligand PD-L1 (B7-H1) and thus interfering with the negative signaling in the T cells that occurs upon engagement of PD-1 with PD-L1-expressing tumors. The resulting rescue of melanoma antigen-specific T cells allows them to carry out their cytotoxic function against tumor cells, and the presence of the ligand on tumor may act as a biomarker predicting the likelihood of clinical benefit from treatment with the antibody (that is, the more dependent this failure of the immune system to control cancer is on PD-L1-PD-1 interactions, the better chance that blocking this interaction will help restore the immune system’s control of cancer). Clinical trials have begun with Phase I dose escalation followed by expansions into several diseases, and promising activity has been observed in advanced melanoma patients who had not previously received ipilimumab. Nearly 1/3 of patients experienced objective responses, many of which were quite durable, and few toxicities occurred. In particular, the blockade of PD-1 interacting with its ligand appears to avoid the widespread, non-specific immune-related toxicities associated with ipilimumab therapy that apparently result from a generalized release of cytotoxic T cells from physiologic (and pathologic) checkpoints on their activity.
New answer by KimMargolinMD (Physician - Oncology - Hematology/Oncology (Verified))
1
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9 months ago
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