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New Developments in Clinical Oncology: The Interdependence of Bench and Bedside¹

Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115

Efforts to diminish the overall morbidity and mortality of malignancy have required a variety of strategies and a balanced national research agenda. The design of curative regimens against leukemia, lymphomas, testis cancer, and childhood malignancies is a tribute to the interactions between laboratory and clinical scientists. Laboratory models illustrated the importance of dose and the need for combinations to avoid the emergence of drug resistance in heterogeneous tumors. In addressing the incurability of common epithelial cancers in adults once disseminated, again laboratory models suggested that regimens which produced responses in advanced disease might be curative in patients with micrometastases. Such proved to be the case in adjuvant therapy for breast cancer involving lymph nodes and for osteogenic sarcoma. Recent studies have extended this strategy to less advanced breast cancer and to locally advanced colon cancer. Lung cancer has required a different strategy. A coalition has developed to support the strongest possible public position against smoking. For the first time lung cancer incidence has leveled off in white males. Women and minorities continue to be a major target for smoking cessation programs. While large randomized trials are expensive (and to some scientists, unexciting), they are our most reliable means of detecting treatment differences of 10 to 15%. Because lung, breast, and colon cancer kill almost 250,000 Americans each year, such "small" differences represent thousands of Americans.

There are also a number of interesting current studies that may impact in the longer term on the care of patients with cancer. Research of three different groups of investigators has recently converged. Over the past 3 decades several groups of basic laboratory investigators had been studying and cloning hematopoietic growth factors. Large randomized trials now confirm that myelosuppression after intensive chemotherapy can be substantially ameliorated, reducing infections and decreasing hospital days, risks, and costs. Another cohort of clinical pharmacologists and clinicians were studying bone marrow transplantation, developing combinations of agents that can be given at high dose to overcome resistance, albeit with considerable toxicity. Other groups in blood banks and those interested in the regulation of hematopoiesis recognized that early bematopoietic progenitor cells circulate in the peripheral blood. Their number were increased after certain chemotherapy regimens, by growth factors and most remarkably, with growth factors given after chemotherapy. Patients supported with peripheral blood progenitor cells reengraft both platelets and granulocytes more rapidly than those given marrow, in the time frame of recovery after standard doses of chemotherapy (i.e., 21 days). Thus for the first time the question of the clinical efficacy of high dose therapy can be addressed at a reasonable cost medically and fiscally.