Curative Cancer Chemotherapy1

Cancer chemotherapy provides variably effective treatment for the majority of forms of human cancer and curative treatment for some 12 categories of cancer. Curative treatment is defined as the proportion of patients who survive beyond the time after which the risk of treatment failure approaches zero, i.e., the disease-free survival plateau. This progress has resulted from a closely integrated scientific effort, including drug development, pharmacology, preclinical modeling, experimental design with respect to clinical trials, quantitative criteria for response, and a series of clinical trials (initially in children with acute lymphocytic leukemia) in which the importance of complete remission, of dose and schedule, of sequencing chemotherapeutic agents, of pharmacological sanctuaries, and particularly of combination chemotherapy was studied. The principles derived from these studies, particularly those relating to combination chemotherapy, resulted in curative treatment for disseminated Hodgkin's dis ease, non-Hodgkin's lymphoma, pediatrie solid tumors, testicular cancer, and limited small cell lung cancer. Many patients with certain stages of solid tumors, such as breast cancer and osteogenic sarcoma, are at high risk of having disseminated micro scopic disease. Experimental studies indicate that treatment which is only partially effective against macroscopic disease is much more effective against microscopic tumors. Therefore chemotherapy is administered immediately following control of the primary tumor in patients at high risk of having disseminated microscopic disease, a treatment known as adjuvant chemo therapy. This program has been highly successful in increasing the cure rate in patients with pediatrie solid tumors and in prolonging disease-free survival in patients with premenopausal breast cancer. Given dissemination of the technology, it is esti mated that 15,000-30,000 patients per year are potentially curable in the United States. Curability of cancer by chemother apy generally is inversely related to age, i.e., the above tumors are most common in children and young adults. There are new and promising treatment strategies, such as neoadjuvant chem otherapy and autologous bone marrow transplantation. The rev olution in molecular and cellular biology is providing an increase in targets, rationale, and opportunity for more effective and novel chemotherapeutic approaches.