Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group
Phase III Trial Comparing Concurrent Biochemotherapy With Cisplatin, Vinblastine, Dacarbazine, Interleukin-2, and Interferon Alfa-2b With Cisplatin, Vinblastine, and Dacarbazine Alone in Patients With Metastatic Malignant Melanoma (E3695): A Trial Coordinated by the Eastern Cooperative Oncology Group
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DOI：
10.1200/jco.2008.17.5448
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发表时间：
2008-12-10
影响因子：
45.3
通讯作者：
Kirkwood, John M.
中科院分区：
文献类型：
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作者：
Atkins, Michael B.;Hsu, Jessie;Kirkwood, John M.
目的生物化疗 (BCT) 的 II 期试验显示出对转移性黑色素瘤的令人鼓舞的缓解率，荟萃分析和一项 III 期试验表明其具有生存获益。为了确定 BCT 与单独化疗相比的相对疗效，美国组间进行了一项 III 期试验。 患者和方法患者被随机分配接受顺铂、长春花碱和达卡巴嗪 (CVD) 单独治疗或与白细胞介素 2 和干扰素 α-2b (BCT) 同时治疗。治疗周期以 21 天的间隔重复，最多四个周期。在第 2 和第 4 周期后评估肿瘤反应，然后每 3 个月评估一次。结果 纳入了 415 名患者，其中 395 名患者（CVD，n = 195；BCT，n = 200）被认为合格且可评估。两个研究组的分层因素和其他预后因素达到了很好的平衡。 BCT 的缓解率为 19.5%，CVD 的缓解率为 13.8% (P = .140)。 BCT 的中位无进展生存期明显长于 CVD（4.8 个月 vs 2.9 个月；P = 0.015），但这并没有转化为中位总生存期（9.0 个月 vs 8.7 个月）或 1 年存活患者百分比（41% vs 36.9%）方面的优势。与 CVD 相比，BCT 导致更多患者经历 3 级或更严重的毒性事件（95% vs 73%；P = 0.001）。 结论 尽管 BCT 的缓解率和中位无进展生存期比单独 CVD 稍高，但这与总体生存率改善或持久缓解无关。考虑到额外的毒性和复杂性，不推荐这种同步 BCT 方案用于转移性黑色素瘤患者。
PurposePhase II trials with biochemotherapy (BCT) have shown encouraging response rates in metastatic melanoma, and meta-analyses and one phase III trial have suggested a survival benefit. In an effort to determine the relative efficacy of BCT compared with chemotherapy alone, a phase III trial was performed within the United States Intergroup.Patients and MethodsPatients were randomly assigned to receive cisplatin, vinblastine, and dacarbazine (CVD) either alone or concurrent with interleukin-2 and interferon alfa-2b (BCT). Treatment cycles were repeated at 21-day intervals for a maximum of four cycles. Tumor response was assessed after cycles 2 and 4, then every 3 months.ResultsFour hundred fifteen patients were enrolled, and 395 patients (CVD, n = 195; BCT, n = 200) were deemed eligible and assessable. The two study arms were well balanced for stratification factors and other prognostic factors. Response rate was 19.5% for BCT and 13.8% for CVD (P = .140). Median progression-free survival was significantly longer for BCT than for CVD (4.8 v 2.9 months; P = .015), although this did not translate into an advantage in either median overall survival (9.0 v 8.7 months) or the percentage of patients alive at 1 year (41% v 36.9%). More patients experienced grade 3 or worse toxic events with BCT than CVD (95% v 73%; P = .001).ConclusionAlthough BCT produced slightly higher response rates and longer median progression-free survival than CVD alone, this was not associated with either improved overall survival or durable responses. Considering the extra toxicity and complexity, this concurrent BCT regimen cannot be recommended for patients with metastatic melanoma.