Pujol J L, Daurès J P, Rivière A, Quoix E, Westeel V, Quantin X, Breton J L, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T
Centre Hôpital Universitaire Arnaud de Villeneuve, Montpellier, France.
J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. doi: 10.1093/jnci/93.4.300.
The combination of etoposide plus cisplatin (EP) is considered to be standard therapy for small-cell lung cancer (SCLC). To determine whether drug intensification improves survival of patients with extensive SCLC, we compared this treatment with a four-drug regimen containing EP plus cyclophosphamide and 4'-epidoxorubicin (PCDE).
In a phase III clinical trial organized by the French Federation of Cancer Institutes, patients were randomly assigned to receive either EP (n = 109; etoposide at a dose of 100 mg/m(2) on days 1-3 plus cisplatin at 100 mg/m(2) on day 2) or PCDE (n = 117; etoposide and cisplatin given as in EP plus cyclophosphamide at 400 mg/m(2) on days 1-3 and 4'-epidoxorubicin at 40 mg/m(2) on day 1) every 4 weeks. Both groups received a total of six cycles. Survival differences were analyzed by Wilcoxon and log-rank tests. Associations of treatment group and putative prognostic variables with survival were tested in the Cox proportional hazards model. Quality of life was assessed from the responses to the European Organization for Research and Treatment of Cancer quality-of-life questionnaire (C30, health status and lung cancer module 13). All statistical tests were two-sided.
Patients in the PCDE arm had a statistically significant higher frequency of combined complete plus partial responses compared with those in the EP arm (21% plus 55% versus 13% plus 48%, respectively; P =.02 for difference in combined objective responses). Patients in the PCDE arm survived longer than those in the EP arm (1-year survival rate: 40% and 29%, respectively; median survival: 10.5 and 9.3 months, respectively; log-rank P =.0067). In the Cox model, the relative risk of death for patients in the PCDE arm compared with those in the EP arm was 0.70 (95% confidence interval = 0.51 to 0.95); the disease also progressed more slowly in patients in the PCDE arm. Hematologic toxicity was higher in the PCDE arm (22% with documented infections compared with 8% in the EP arm; P =.0038), and the toxicity-related death rate was 9% in the PCDE arm versus 5.5% in the EP arm (P =.22). The global health status showed similar improvement in both arms during treatment.
Compared with the EP regimen, the PCDE regimen yielded higher response rates and better survival rates in patients with extensive SCLC without affecting the quality of life of the patients during chemotherapy.
依托泊苷联合顺铂（EP）被认为是小细胞肺癌（SCLC）的标准治疗方案。为了确定药物强化是否能提高广泛期SCLC患者的生存率，我们将这种治疗方法与包含EP加环磷酰胺和表柔比星（PCDE）的四联方案进行了比较。
在法国癌症研究所联合会组织的一项III期临床试验中，患者被随机分配接受EP方案（n = 109；第1 - 3天给予依托泊苷100 mg/m²，第2天给予顺铂100 mg/m²）或PCDE方案（n = 117；依托泊苷和顺铂的给药方式同EP方案，加第1 - 3天给予环磷酰胺400 mg/m²，第1天给予表柔比星40 mg/m²），每4周重复一次。两组均共接受六个周期的治疗。通过Wilcoxon检验和对数秩检验分析生存差异。在Cox比例风险模型中检验治疗组和假定的预后变量与生存的相关性。根据对欧洲癌症研究与治疗组织生活质量问卷（C30，健康状况和肺癌模块13）的回答评估生活质量。所有统计检验均为双侧检验。
与EP组相比，PCDE组患者完全缓解加部分缓解的联合频率在统计学上显著更高（分别为21% + 55% 与13% + 48%；联合客观缓解率差异P = 0.02）。PCDE组患者的生存期长于EP组（1年生存率分别为40%和29%；中位生存期分别为10.5个月和9.3个月；对数秩检验P = 0.0067）。在Cox模型中，PCDE组患者与EP组患者相比的死亡相对风险为0.70（95%置信区间 = 0.51至0.95）；PCDE组患者的疾病进展也更慢。PCDE组的血液学毒性更高（记录有感染的患者为22%，而EP组为8%；P = 0.0038），PCDE组与毒性相关的死亡率为9%，而EP组为5.5%（P = 0.22）。治疗期间两组的总体健康状况改善相似。
与EP方案相比，PCDE方案在广泛期SCLC患者中产生了更高的缓解率和更好的生存率，且不影响化疗期间患者的生活质量。
