Flaherty L E
Karmanos Cancer Institute, Wayne State University, Detroit, Michigan 48201, USA.
Cancer J Sci Am. 2000 Feb;6 Suppl 1:S15-20.
The modest activity of chemotherapy and biologic agents in the treatment of advanced metastatic melanoma has prompted investigators to consider combinations of chemotherapy and biologic agents (i.e., biochemotherapy) as a way of improving response rates and survival. Although biochemotherapy has generated a great deal of interest over the last several years, and these regimens have produced high response rates in single-institution phase II trials, they have yet to demonstrate a significant survival benefit in randomized trials compared with either chemotherapy or biotherapy alone.
The available literature regarding the clinical experience with single- and multiagent chemotherapy, immunotherapy, and biochemotherapy was reviewed.
Treatment of metastatic melanoma with either single-agent or combination chemotherapy regimens is clearly suboptimal; the majority of responses are partial and of short duration. In contrast, interleukin (IL)-2 produces long-term durable complete remission in a subset of patients. Over 1,000 patients have been treated with IL-2-based biochemotherapy regimens in single-institution phase II trials, and response rates have ranged from 40% to 60%. Most encouraging have been the durable responses observed in 10% to 20% of patients in most of these trials. Large databases, including two meta-analyses, have confirmed the substantial improvement in response rate associated with biochemotherapy regimens that include both IL-2 and interferon alfa (IFN-alpha) compared with chemotherapy or biotherapy alone. Biochemotherapy is currently being evaluated in randomized controlled trials to determine if this treatment strategy can provide a survival benefit compared with current standard treatments. A pilot study at Beth Israel Deaconess Medical Center has demonstrated the feasibility of administering a modification of a concurrent biochemotherapy regimen, initially described by Legha et al, consisting of cisplatin, vinblastine, and dacarbazine (CVD) plus IL-2 and IFN-alpha in the cooperative group setting.
These studies provided the rationale for intergroup trial E-3695, which is currently randomizing patients to concurrent biochemotherapy with CVD plus IL-2 and IFN-alpha versus CVD alone.
化疗和生物制剂在晚期转移性黑色素瘤治疗中的效果有限，促使研究人员考虑将化疗与生物制剂联合使用（即生物化疗），以期提高缓解率和生存率。尽管在过去几年中生物化疗引起了广泛关注，且这些方案在单机构II期试验中产生了较高的缓解率，但与单纯化疗或生物治疗相比，它们在随机试验中尚未显示出显著的生存获益。
回顾了有关单药和多药化疗、免疫治疗及生物化疗临床经验的现有文献。
使用单药或联合化疗方案治疗转移性黑色素瘤显然并非最佳选择；大多数缓解为部分缓解且持续时间较短。相比之下，白细胞介素（IL）-2可使一部分患者实现长期持久的完全缓解。在单机构II期试验中，超过1000例患者接受了基于IL-2的生物化疗方案治疗，缓解率在40%至60%之间。最令人鼓舞的是，在大多数此类试验中，10%至20%的患者出现了持久缓解。包括两项荟萃分析在内的大型数据库证实，与单纯化疗或生物治疗相比，包含IL-2和干扰素α（IFN-α）的生物化疗方案在缓解率方面有显著提高。目前正在进行随机对照试验以评估生物化疗，以确定该治疗策略与当前标准治疗相比是否能带来生存获益。贝斯以色列女执事医疗中心的一项初步研究证明了在协作组环境中实施由Legha等人最初描述的同步生物化疗方案改良版的可行性，该方案由顺铂、长春碱和达卡巴嗪（CVD）加IL-2和IFN-α组成。
这些研究为组间试验E-3695提供了理论依据，该试验目前正在将患者随机分为接受CVD加IL-2和IFN-α的同步生物化疗与单纯CVD治疗两组。
