Biomedical subjects
BA Chabner
Publications and source records attributed to BA Chabner.
Promising New Drugs and Combinations. Fulfilling Our Pledge.
We are fortunate, as physicians and clinical researchers, to live in a time of unprecedented expansion of treatment approaches. Much of this change is due to the application of new knowledge regarding the causes of malignant transformation and progression, and the pace of research and its application is likely to quicken. The pace of change is exemplified by the number and variety of new drugs that will transform treatment of cancer in the next few years: antibodies for breast cancer and lymphoma, differentiating agents for acute promyelocytic leukemia, molecularly targeted agents for chronic myelocytic leukemia, antiangiogenic drugs, antimetastatic agents, and new natural products with unique mechanisms of action. Some are already approved and in routine use, while others are progressing rapidly through the pre-approval process. All of this change presents a challenge to the practicing oncologist who must understand the biology, pharmacology, and clinical uses of the new drugs. What are the advantages, limitations, risks, and benefits of the drugs, how do they interact with other drugs and with irradiation, and how are they likely to be used in the future? To provide timely access to this information, The Oncologist has asked its board of editors to develop a new section of the Journal that will be devoted to Promising New Drugs and Combinations. Two experienced and highly respected clinical researchers, Frank Balis, Chief of the Pharmacology and Experimental Section in the Pediatrics Branch at the National Cancer Institute, and Michael Hawkins, Associate Director at the Washington Hospital Center Cancer Institute, have agreed to edit and oversee this section of the journal and will make sure that our readership has essential information on new drugs as they approach marketing status. Please let us know if we are providing useful and timely information. We value your suggestions for making The Oncologist the most relevant of all the journals you read.
ASCO 1998: A Commentary.
The American Society of Clinical Oncology (ASCO) occupies a central place in the professional and social life of cancer specialists. In this once-a-year happening we have the opportunity to see close colleagues from the past and reflect on the state of our profession, including clinical research and the more practical aspects of our existence and survival as practitioners. Robert Mayer, the outgoing ASCO President, and the Program Chair, Margaret Shipp, did a masterful job of creating a well-organized, informative, and exciting four days in Los Angeles. ASCO is an organization in evolution. While clinical research is still its main mission, the financial and organizational aspects of cancer care occupy an increasingly important place in this meeting, as reflected in the program itself and in the dominating presence of the drug companies on the exhibit runways. Nonetheless, the quality of the scientific sessions was outstanding.
Schwartz Center Rounds. A Staff Dialogue on Phase I Trials: Psychosocial Issues Faced by Patients, Their Families, and Caregivers.
Shortly before his death in 1995, Kenneth B. Schwartz, a cancer patient at Massachusetts General Hospital, founded The Kenneth B. Schwartz Center to be housed at Massachusetts General Hospital (MGH). He created this center to advance the hopes, goals, and ideas expressed in his article, "A Patient's Story," published in the July 16, 1995 issue of the Boston Globe Magazine. The Schwartz Center is a non-profit organization dedicated to strengthening the relationship between patients and caregivers and to supporting and advancing "compassionate health care delivery in which caregivers, patients and their families relate meaningfully to one another in a way that provides hope to the patient, support to caregivers and sustenance to the healing process." One of the Center's major projects is the sponsoring of the Schwartz Center Rounds, a monthly, multidisciplinary forum in which caregivers discuss a specific cancer patient and the important psychosocial issues faced by the patient, family and caregivers. The forum allows caregivers to reflect on their experiences with patients and to gain support and insight from fellow staff members. The following case discussion was addressed at the January 1998 Schwartz Center Rounds. In this article, the case will be presented, followed by verbatim dialogue from the rounds and a subsequent discussion of the relevant issues with emphasis on staff psychosocial issues. J.T. was a 43-year-old man who developed adenocarcinoma of the lung and was treated at MGH. He died while participating in a phase I trial, resulting in marked frustration and distress among his caregivers. Staff questioned whether cancer patients entering phase I trials and their families receive unbiased information about the possible risks and benefits of the trial. They were also concerned about whether or not patients and their families really understand the physical and emotional risks of a trial. Moreover, they addressed whether patients are presented with alternatives to enrolling in a phase I trial, such as palliative care. Despite all these concerns, caregivers are reconciled to the belief that patients do value the opportunity to participate in phase I trials, in that they can contribute hope and meaning to other patients' struggles with cancer.
Schwartz Center Rounds. A Staff Dialogue on Caring for an Intensely Spiritual Patient: Psychosocial Issues Faced By Patients, Their Families, and Caregivers.
The Schwartz Center Rounds are a monthly multidisciplinary forum, at Massachusetts General Hospital (MGH), in which caregivers discuss a specific patient with cancer and the important psychosocial issues faced by the patient, family, and caregivers. This forum allows caregivers to reflect on their experiences with patients and to gain support and insight from their fellow staff members. The following case discussion was addressed at the September 1997 Schwartz Center Rounds. M.R. was a 45-year-old woman who developed ovarian carcinoma and was subsequently treated at MGH. She was a deeply religious woman and believed that God would cure her cancer. Her religious views profoundly influenced her decisions related to further care and her ability to accept what staff felt to be a realistic assessment of her condition and progress. At the rounds, staff members struggled with many issues, including whether M.R. should continue her treatment at MGH or return home to Puerto Rico. Staff found it challenging to discuss a sensitive topic-such as spirituality-with a patient, especially when the patient was from a different cultural background. One of the most striking outcomes of the rounds was the diversity of staff views regarding how they advocated addressing spirituality with a patient. Staff concluded that discussion of spirituality-while challenging-can meaningfully enhance the caregiver-patient relationship.
Cancer: A Personal Journey. Notes from the Edge.The Diary of Peter J. Morgan, M.D.
It is a mistake to think that all personal experiences with cancer are the same. For certain, all cancer patients do confront the possibility of an early death and the prospect of pain and suffering due to the tumor and its treatment. But the specific emotional issues differ with each patient and each family, and the responses to these issues take many forms. In an eloquent and moving film, "Cancer: A Personal Journey. Notes from the Edge.," we are given the privilege of accompanying a remarkable young physician, Peter J. Morgan, on his journey with cancer, a two and one-half year journey that ended with his death at age 31. At age 29, Dr. Morgan, an internist-in-training who intended to pursue a career in hematology and oncology, noted a mass on his leg. Tragically, metastasis to the lungs had already taken place at the time of diagnosis of a synovial sarcoma. There followed the all-too-familiar story of chemotherapy and experimental treatments, pain, debilitation, and ultimately demise, and in itself this experience would move us with the sorrow of a precious life lost. What makes this particular story so remarkable are the insights of this young physician and the struggle for survival of a spirit that would not succumb to the "chaos" of cancer. In the two-year period of his life as a cancer patient, Peter Morgan kept a diary that records his thoughts, his emotional turmoil, and his reflections on life and an untimely death. In particular, we are able to understand the need for his spiritual self to remain alive and to grow despite the deterioration of his physical being. And we see that spiritual triumph in his compelling relationships with his family and his colleagues, in his reflections on art and music and nature, and most of all in his writings and his appreciation of the immense possibilities for joy in life. This is not an easy journey to watch, but the intense sadness of his experience is balanced by his friendships and the great satisfaction he derived from patient care until the end of his own illness. We hear accounts of his leaving his hospital bed in New York City, where he has received an infusion of chemotherapy, and driving across Long Island to volunteer at a university out-patient clinic in Stonybrook. During the last year of his life, he becomes a beloved teacher and attending physician in this clinic. One is left with the feeling that Peter Morgan has learned a great deal about what is important and beautiful in this life. The filmmaker, Ruth Yorkin Drazen, and the narrator, Matthew Broderick, have created a masterpiece. I can remember only one other movie, "Shadowland," the story of C.S. Lewis's marriage and the loss of his wife due to cancer, that speaks as eloquently to the confrontation with cancer. In that film, one is left with the overwhelming sorrow of the husband. The present film goes far beyond many of the personal narratives about cancer experiences that one finds so often in the media, simply because it allows a remarkable individual to speak to us about what was most precious in his life. For those of us in the medical profession, his message is particularly meaningful: his work as a physician was at the top of his list.
Back to the Future for Clinical Oncology.
Dear Colleague: I remember, but just barely, what it was like to practice medicine in the first half of this century. My Dad was a general practitioner in a very small farming community in central Illinois, with a hospital of six beds and a trusting clientele. His patients thought he knew how to do everything: deliver babies, set broken bones and take out an appendix. He was an advocate for his patients, not for an HMO or an insurance company. He derived great satisfaction from his practice and was comfortable in this role, up to a point, but knew that he frequently needed the help of specialists from Decatur, St. Louis, and the Mayo Clinic. As his experience and practice evolved, and as medicine itself changed, referrals became a sign of good practice and not an indication of weakness or inadequacy. Some doctors in our town continued to do more than they should have and resisted the trend, and their patients, many with blind faith in their doctor, suffered for it. Clearly, there were economic as well as emotional factors that contributed to this reluctance to ask for help. Clinical oncology is facing much the same situation today. Scientific and economic forces are revolutionizing medicine, but not always in compatible directions. Practice and research have evolved to the point where old patterns of practice are no longer optimal. Few cancer patients can be managed without the input, advice, and even direct involvement of specialists from sister disciplines. Thus, multimodality management of cancer patients is now the norm rather than the exception. At the same time, strong economic forces are dictating a movement in the opposite direction, undermining the strength of traditional academic centers and limiting choices, streamlining patient evaluation, and creating "pathways" to standardize patient management. Who should be setting the course for the cancer patient? We agree that it should not be a clerk at the other end of the phone at the HMO, a computerized practice manual, or even the gatekeeper, who watches his or her capitated bottom line with great nervousness. It should be the physician(s) best able to evaluate the alternatives and communicate these choices to the patient and family. Often it is not possible for a solo physician to make these choices in isolation, particularly when the decisions involve multiple specialties and multimodality therapies. At presentation, many primary cancers now require an integration of the opinion of more than one specialist, and increasingly this integration occurs before surgery. Breast, lung, and prostate cancer, three of our most common diseases, illustrate this point with growing clarity. While less convenient for the doctor, and perhaps less efficient than the "old style" of practice, multimodatity disease center clinics offer significant advantages both to the patient and to the research effort, and are here to stay. Certainly for the payer it is faster and cheaper to have one doctor do it all, but I doubt that the results will be as good. Obviously not all patients need this cooperative approach. It would waste good physicians' time to require that all patients be seen by a radiotherapist, surgeon, and medical oncologist or pediatric oncologist. The specific circumstances may clearly dictate a simple approach and an uncomplicated decision, particularly in dealing with metastatic solid tumors, or at the other extreme, in managing easily resectable, low-risk tumors. However, even here, optimal management of local disease or of potentially resectable metastases may require consideration of an expanded series of options. Thus, all cancer specialists need to be aware of the potential of their colleagues to contribute to disease management. ellipsisWhich brings us to the reason for this journal. The editorial board members of The Oncologist hold the belief that the various subspecialists in oncology should share the same information base and read from the same journal. We believe that cancer specialists should resist the trend to capitulate our responsibilities in disease management to payers, gatekeepers, and hospital administrators. It is up to us to defend the patient's turf and to assure that the patient has an advocate. In order to do so, we will have to be united and fully informed. In this journal, we hope to put the best and latest information on cancer management before our readership, to prepare them for the future, and to do their best as a team for every patient. To this end, we hope to challenge the reader to understand what is new and better, and to let you glimpse the future, not only in terms of research, but also in terms of new team approaches to disease management. We hope to explore how cancer medicine could be and will be practiced as we pass through the economic revolution and return to the future.
Purine Analogs for the Treatment of Low-Grade Lymphoproliferative Disorders.
PRIMARY PURPOSE: Low-grade lymphoproliferative disorders follow an indolent clinical course but are incurable with current therapy. Recently, three active agents for the treatment of these diseases have been identified: the purine analogs fludarabine, pentostatin and 2-chlorodeoxyadenosine. The purpose of this review is to summarize the current knowledge on the mechanism of action, clinical activity and toxicities of the purine analogs. METHODS: Articles, abstracts and letters to the editor appearing in English literature and involving the use of the purine analogs in the treatment of hairy cell leukemia, chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma, cutaneous T cell lymphomas and Waldenstrom's macroglobulinemia were reviewed. RESULTS AND CONCLUSION: Purine analogs have marked cytoreductive potential in the treatment of chronic lymphocytic leukemia, indolent non-Hodgkin's lymphoma and hairy cell leukemia. Major side effects include myelosuppression and infections. Profound lymphocytopenia can be sustained, predisposing patients to opportunistic infections. Although remissions achieved with these agents can be long-lasting, minimal residual disease frequently persists. Postremission strategies aimed at eradicating such microscopic diseases can potentially improve the results of purine analog therapy. Alternatively, the up-front combination of these agents with traditional chemotherapy may lead to higher response rates and more sustained remissions.