Westeel Virginie, Quoix Elisabeth, Moro-Sibilot Denis, Mercier Mariette, Breton Jean-Luc, Debieuvre Didier, Richard Philippe, Haller Mary-Anne, Milleron Bernard, Herman Dominique, Level Marie-Claude, Lebas François-Xavier, Puyraveau Marc, Depierre Alain
Chest Disease Department, Jean Minjoz University Hospital, Besançon, France.
J Natl Cancer Inst. 2005 Apr 6;97(7):499-506. doi: 10.1093/jnci/dji096.
Prolongation of chemotherapy duration, usually referred to as maintenance chemotherapy, has been considered as an approach to improve survival of patients with advanced non-small-cell lung cancer (NSCLC). If the maintenance regimen differs from the induction regimen, patients will receive not only higher total doses of chemotherapy but also earlier delivery of non-cross-resistant agents. We conducted a randomized trial to compare maintenance vinorelbine therapy with observation in previously untreated patients who responded to induction treatment with mitomycin-ifosfamide-cisplatin (MIC).
Patients with stage IIIB NSCLC were treated with two monthly MIC cycles followed by radiotherapy; those with "wet" stage IIIB (pleural or pericardial involvement), with stage IIIB with supraclavicular node involvement, or stage IV (i.e., metastatic) NSCLC were treated with four monthly MIC cycles. Patients who responded to induction treatment were randomly assigned to receive intravenous vinorelbine at a dose of 25 mg x m(-2) x wk(-1) for 6 months or no further treatment. Survival comparisons used the log-rank test and the Cox regression adjusted for stage. All statistical tests were two-sided.
A total of 573 patients were registered, of whom 227 responded to induction treatment and 181 were randomly assigned (91 to maintenance vinorelbine and 90 to observation) between January 1994 and March 2000. One- and 2-year survival rates were 42.2% and 20.1% in the vinorelbine arm and 50.6% and 20.2% in the observation arm, respectively (log-rank P = .48). The hazard ratio of survival after adjustment on stage, in the vinorelbine arm relative to the observation arm, was 1.08 (95% confidence interval = 0.79 to 1.47; P = .65). There was also no difference between arms in progression-free survival (log-rank P = .32).
Maintenance vinorelbine did not improve survival of patients with advanced NSCLC who responded to induction MIC treatment. Nevertheless, other agents, including docetaxel and targeted agents, should be evaluated as maintenance agents before the concept is abandoned.
化疗疗程的延长，通常称为维持化疗，已被视为提高晚期非小细胞肺癌（NSCLC）患者生存率的一种方法。如果维持方案与诱导方案不同，患者不仅会接受更高的化疗总剂量，还会更早地使用非交叉耐药药物。我们进行了一项随机试验，比较长春瑞滨维持治疗与观察在接受丝裂霉素-异环磷酰胺-顺铂（MIC）诱导治疗有效的初治患者中的疗效。
IIIB期NSCLC患者接受两个月的MIC周期治疗，随后进行放疗；“湿性”IIIB期（胸膜或心包受累）、伴有锁骨上淋巴结受累的IIIB期或IV期（即转移性）NSCLC患者接受四个月的MIC周期治疗。对诱导治疗有反应的患者被随机分配接受静脉注射长春瑞滨，剂量为25mg×m(-2)×wk(-1)，持续6个月，或不再接受进一步治疗。生存比较采用对数秩检验和根据分期调整的Cox回归。所有统计检验均为双侧检验。
共登记573例患者，其中227例对诱导治疗有反应，1994年1月至2000年3月期间，181例被随机分配（91例接受长春瑞滨维持治疗，90例接受观察）。长春瑞滨组的1年和2年生存率分别为42.2%和20.1%，观察组分别为50.6%和20.2%（对数秩检验P = 0.48）。根据分期调整后，长春瑞滨组相对于观察组的生存风险比为1.08（95%置信区间 = 0.79至1.47；P = 0.65）。两组在无进展生存期方面也没有差异（对数秩检验P = 0.32）。
长春瑞滨维持治疗未能提高对诱导MIC治疗有反应的晚期NSCLC患者的生存率。然而，在放弃这一概念之前，应评估其他药物，包括多西他赛和靶向药物作为维持药物的疗效。
