Bonadonna G
Cancer Res. 1982 Nov;42(11):4309-20.
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.
本文综述了霍奇金病中晚期的新化疗策略，以及近期生物学概念和数学模型在新治疗方案的解释与设计中所具有的意义。阿霉素-博来霉素-长春花碱-达卡巴嗪（ABVD）联合方案的研发与应用，是基于对氮芥-长春新碱-丙卡巴肼-泼尼松（MOPP）联合方案的利弊进行批判性重新评估的结果。起初，开发非交叉耐药方案（如ABVD）的尝试是出于改善对MOPP耐药患者的挽救治疗的愿望而直观产生的；最近，戈尔迪和戈德曼（《癌症治疗报告》，63: 1727 - 1733, 1979）提出了该方法的理论框架。不同形式的挽救化疗以及非交叉耐药联合方案（MOPP和ABVD）的循环给药所取得的5年结果，在很大程度上可以通过以下假设来解释：耐药突变体是化疗治愈霍奇金病以及其他肿瘤的主要限制因素。一项前瞻性随机试验的初步结果表明，将非交叉耐药方案作为一线治疗给药是一种合理且有力的战略方法，因此它可能构成临床研究的一个重要途径。近期的观察还强调了生活质量问题，因为不包含烷化剂和/或丙卡巴肼的多药联合给药似乎与致癌和不育发生率的降低相关。摒弃将单一多药方案用于霍奇金病化疗的标准做法，应该得到基于已知疗效和毒性的药物联合的可靠研究和对照研究的支持。
