Chemotherapy strategies to improve the control of Hodgkin's disease: the Richard and Hinda Rosenthal Foundation Award Lecture

Abstract

The paper reviews new chemotherapy strategies for intermediate and advanced stages of Hodgkin's disease as well as the implications of recent biological concepts and mathematical models which appear useful in the interpretation and design of new treatments. The development and the application of the Adriamycin-bleomycin-vinblastine-dacarbazine (ABVD) combination was based on critical reevaluation of benefits and limits of the mechlorethamine-vincristine-procarbazine-prednisone (MOPP) combination. The attempts to develop non-cross-resistant regimens, such as ABVD, arose intuitively at first from the desire to improve salvage treatment in MOPP-refractory patients; more recently, a theoretical framework for this approach has been proposed by Goldie and Coldman (Cancer Treat. Rep., 63: 1727-1733, 1979). The 5-year results achieved with different forms of salvage chemotherapy and with the cyclic delivery of non-cross-resistant combinations (MOPP and ABVD) can be explained largely by the assumption that drug-resistant mutants represent a major limiting factor in the cure of Hodgkin's disease, as well as of other neoplasms, by chemotherapy. The initial results from a prospective randomized trial indicate that the administration as front-line therapy of non-cross-resistant regimens is a logical and powerful strategic approach and therefore that it may constitute an important avenue of clinical research. Recent observations also emphasized the problem of the quality of life, since the administration of multidrug combinations not including alkylating agents and/or procarbazine appears to be associated with a decreased incidence of carcinogenesis and sterility. The departure from the standard practice of utilizing a single multidrug regimen for chemotherapy of Hodgkin's disease should be supported by sound research and controlled studies built on drug combinations of known efficacy and toxicity.