Johnson D H, Bass D, Einhorn L H, Crawford J, Perez C A, Bartolucci A, Omura G A, Greco F A
Vanderbilt University School of Medicine, Nashville, TN 37232-5536.
J Clin Oncol. 1993 Jul;11(7):1223-9. doi: 10.1200/JCO.1993.11.7.1223.
The primary objective of this randomized prospective study was to compare the survival of limited-stage small-cell lung cancer (SCLC) patients treated with chemotherapy alone or chemotherapy plus thoracic radiotherapy (TRT). A secondary objective was to determine the effect of consolidation chemotherapy on survival.
This multiinstitutional phase III study included 386 patients with limited-stage SCLC. All patients received cyclophosphamide 1,000 mg/m2, doxorubicin 40 mg/m2, and vincristine 1 mg/m2 (CAV) every 3 weeks for six cycles. Irradiated patients received 30 Gy in 10 fractions during weeks 1 and 2 of chemotherapy. Fifteen Gy in five fractions was administered during week 7 (total dose, 45 Gy). Following CAV, responding patients were randomized to receive two cycles of consolidation chemotherapy (cisplatin 20 mg/m2/d for 4 days plus etoposide 100 mg/m2/d for 4 days) or observation.
Complete (46% and 38%; P = .14) and overall response rates (67% and 64%; P = .58) were not statistically significantly different. Although not significantly different, median (14.4 v 12.8 months) and 2-year survival (33% v 23.5%) rates favored the irradiated patients. Grade 4 hematologic toxicity was greater in irradiated patients (60% and 39%; P < .001). Patients given consolidation chemotherapy experienced superior median (21.1 v 13.2 months; P = .028) and 2-year survival (44% v 26%; P = .028) rates.
The concurrent use of TRT and CAV chemotherapy as administered in this study failed to improve the survival of limited-stage SCLC patients compared with CAV alone. Life-threatening hematologic toxicities were more frequent with combined-modality therapy. The survival of limited-stage patients treated with CAV (with or without TRT) was improved with two cycles of cisplatin and etoposide consolidation therapy. Whether similar survival results could be achieved with cisplatin and etoposide alone requires additional study.
本随机前瞻性研究的主要目的是比较单纯化疗或化疗加胸部放疗（TRT）治疗局限期小细胞肺癌（SCLC）患者的生存率。次要目的是确定巩固化疗对生存率的影响。
这项多机构III期研究纳入了386例局限期SCLC患者。所有患者每3周接受环磷酰胺1000mg/m²、阿霉素40mg/m²和长春新碱1mg/m²（CAV），共六个周期。接受放疗的患者在化疗的第1周和第2周分10次给予30Gy照射。在第7周给予5次分割的15Gy（总剂量45Gy）。CAV化疗后，缓解的患者被随机分为接受两个周期的巩固化疗（顺铂20mg/m²/天，共4天加依托泊苷100mg/m²/天，共4天）或观察。
完全缓解率（46%和38%；P = 0.14）和总缓解率（67%和64%；P = 0.58）在统计学上无显著差异。虽然差异不显著，但中位生存期（14.4对12.8个月）和2年生存率（33%对23.5%）放疗组更优。放疗患者4级血液学毒性更高（60%和39%；P < 0.001）。接受巩固化疗的患者中位生存期（21.1对13.2个月；P = 0.028）和2年生存率（44%对26%；P = 0.028）更优。
本研究中同时使用TRT和CAV化疗与单纯CAV化疗相比，未能提高局限期SCLC患者的生存率。联合治疗危及生命的血液学毒性更常见。两个周期的顺铂和依托泊苷巩固治疗可提高接受CAV（无论是否联合TRT）治疗的局限期患者的生存率。单独使用顺铂和依托泊苷是否能取得相似的生存结果需要进一步研究。
