High-Dose Chemotherapy in Adult Solid Tumors and Lymphoproliferative Disorders: The Need for Randomized Trials

The demonstration of a dose-effect relationship in a wide spectrum of malignancies including solid tumors and lymphoproliferative disorders, along with the development of new techniques of hematopoietic stem cell support, have given rise to a growing interest for high-dose chemotherapy in recent years. Results in more than 3,000 patients included in nonrandomized trials have been reported in the literature. However, only nine randomized trials addressing the issue of the impact of high-dose chemotherapy on survival have been published: three in non-Hodgkin's lymphoma, one in multiple myeloma, two in metastatic breast cancer, one in germ-cell tumors, one in melanoma, and one in small-cell lung cancer. Firm, reliable conclusions can only be drawn from studies conducted in the salvage treatment of non-Hodgkin's lymphoma and in the first-line treatment of multiple myeloma: high-dose chemotherapy used in a consolidation setting after conventional chemotherapy leads to a survival advantage in chemosensitive patients. Promising but not firmly conclusive results were reported in metastatic breast cancer. The results of the sixteen ongoing randomized trials as well as studies addressing the issue of cost-effectiveness will be critical in establishing definite conclusions on the role of high-dose chemotherapy. With the exception of multiple myeloma and relapsed non-Hodgkin's lymphoma, there is no evidence for treating patients with high-dose chemotherapy outside randomized clinical trials.