Hong W K, Nicaise C, Lawson R, Maroun J A, Comis R, Speer J, Luedke D, Hurtubise M, Lanzotti V, Goodlow J
University of Texas M.D. Anderson Cancer Center, Department of Medical Oncology, Houston 77030.
J Clin Oncol. 1989 Apr;7(4):450-6. doi: 10.1200/JCO.1989.7.4.450.
A total of 353 patients with previously untreated small-cell lung cancer (SCLC) were accrued in this multicenter trial. Patients were randomly assigned to receive one of the following three regimens: cyclophosphamide 1,000 mg/m2 intravenously (IV) day 1, vincristine 1.4 mg/m2 IV day 1, and etoposide 50 mg/m2 IV day 1, followed by etoposide 100 mg/m2/day orally days 2 through 5 (CEV); cyclophosphamide 1,000 mg/m2 IV day 1, vincristine 1.4 mg/m2 IV day 1, and doxorubicin 50 mg/m2 IV day 1 (CAV); cyclophosphamide 2,000 mg/m2 day 1 and vincristine 1.4 mg/m2 IV day 1 (CV). Cycles were repeated every 3 weeks. Treatment groups were comparable with respect to extent of disease, age, sex, performance status, and metastatic sites. No significant differences in response rates, response duration, or survival could be detected in limited disease, although there appeared to be a trend favoring CEV. Among extensive-disease patients, response duration on the CEV regimen was longer than on the CV regimen or the CAV program (P less than .001). The superiority of the CEV regimen was also demonstrated in the survival analysis in which differences attained statistical significance (P = .01). In this group the median survival was increased from 29 weeks on CV to 31 weeks on CAV and 39 weeks on CEV. Myelosuppression was the most frequent toxicity. It was more severe with CV than CEV or CAV. Most nonhematologic side effects were comparable among the three treatment groups. However, the high doses of cyclophosphamide in the CV regimen produced a higher incidence of hemorrhagic cystitis than in the CEV or CAV programs (P less than .001). Cardiotoxicity only occurred in the CAV group (P = .05). The addition of etoposide to the CV regimen resulted in significantly longer response duration and survival without increased toxicity. Similarly, the substitution of etoposide for the doxorubicin in the CAV regimen was associated with prolonged survival and reduced cardiotoxicity.
在这项多中心试验中，共纳入了353例既往未接受过治疗的小细胞肺癌（SCLC）患者。患者被随机分配接受以下三种治疗方案之一：环磷酰胺1000mg/m²静脉注射（IV）第1天、长春新碱1.4mg/m² IV第1天、依托泊苷50mg/m² IV第1天，随后依托泊苷100mg/m²/天口服第2至5天（CEV）；环磷酰胺1000mg/m² IV第1天、长春新碱1.4mg/m² IV第1天、阿霉素50mg/m² IV第1天（CAV）；环磷酰胺2000mg/m²第1天和长春新碱1.4mg/m² IV第1天（CV）。每3周重复一个周期。治疗组在疾病范围、年龄、性别、体能状态和转移部位方面具有可比性。在局限性疾病中，未检测到缓解率、缓解持续时间或生存率的显著差异，尽管似乎有倾向于CEV的趋势。在广泛期疾病患者中，CEV方案的缓解持续时间长于CV方案或CAV方案（P<0.001）。CEV方案的优越性在生存分析中也得到了证实，差异具有统计学意义（P = 0.01）。在该组中，中位生存期从CV方案的29周增加到CAV方案的31周和CEV方案的39周。骨髓抑制是最常见的毒性反应。CV方案比CEV或CAV方案更严重。大多数非血液学副作用在三个治疗组中相当。然而，CV方案中环磷酰胺的高剂量导致出血性膀胱炎的发生率高于CEV或CAV方案（P<0.001）。心脏毒性仅发生在CAV组（P = 0.05）。在CV方案中加入依托泊苷可显著延长缓解持续时间和生存期，且不增加毒性。同样，在CAV方案中用依托泊苷替代阿霉素与生存期延长和心脏毒性降低相关。
