Gandara D R, Crowley J, Livingston R B, Perez E A, Taylor C W, Weiss G, Neefe J R, Hutchins L F, Roach R W, Grunberg S M
University of California-Davis, Sacramento.
J Clin Oncol. 1993 May;11(5):873-8. doi: 10.1200/JCO.1993.11.5.873.
To test the concept that cisplatin dose-intensity is important in the treatment of non-small-cell lung cancer (NSCLC), the Southwest Oncology Group (SWOG) performed a randomized trial comparing standard-dose cisplatin (SDCP) 50 mg/m2 days 1 and 8 on a 28-day cycle for eight cycles, high-dose cisplatin (HDCP) 100 mg/m2 days 1 and 8 for four cycles, and high-dose cisplatin plus mitomycin (HDCP-M) 8 mg/m2 day 1. To isolate the effects of dose-intensity versus total dose, the planned cumulative cisplatin dose was 800 mg/m2 in each arm.
Between July 1988 and April 1990, 356 patients were enrolled and 323 were eligible and assessable. All patients had metastatic, measurable disease, were chemotherapy-naive, and had a performance status (PS) of 0 to 2.
Confirmed complete plus partial response rates were SDCP, 12%; HDCP, 14%; and HDCP-M, 27% (P < .05). Complete responses were uncommon (HDCP, 3%; HDCP-M, 4%) and were observed only in the high-dose arms. Progressive disease occurred more frequently in the SDCP arm (57%) compared with HDCP (38%) or HDCP-M (34%) (P < .05). However, there were no significant differences in median survival times (SDCP, 6.9 months; HDCP, 5.3 months; HDCP-M, 7.2 months; P = .53). The mean delivered dose-intensity for cisplatin was significantly greater in the high-dose arms: HDCP 41 mg/m2/wk and HDCP-M 39 mg/m2/wk, versus SDCP 23 mg/m2/wk (P = .05). The high-dose arms resulted in an increased incidence of ototoxicity, emesis, and myelosuppression, but similar degrees of renal toxicity and neuropathy compared with SDCP.
This study does not confirm evidence of a steep clinical dose-response curve for cisplatin in NSCLC at the cisplatin dose-intensities achieved. The addition of mitomycin increases the response rate, but does not improve survival. Continued evaluation of new agents in this disease is warranted.
为验证顺铂剂量强度在非小细胞肺癌（NSCLC）治疗中具有重要性这一概念，西南肿瘤协作组（SWOG）开展了一项随机试验，比较标准剂量顺铂（SDCP），每28天为一个周期，第1天和第8天给予50mg/m²，共8个周期；高剂量顺铂（HDCP），每28天为一个周期，第1天和第8天给予100mg/m²，共4个周期；以及高剂量顺铂加丝裂霉素（HDCP-M），第1天给予8mg/m²。为分离剂量强度与总剂量的影响，各治疗组计划的顺铂累积剂量均为800mg/m²。
1988年7月至1990年4月期间，共纳入356例患者，其中323例符合条件且可进行评估。所有患者均有转移性、可测量病灶，既往未接受过化疗，且体能状态（PS）为0至2。
确认的完全缓解加部分缓解率分别为：SDCP组12%；HDCP组14%；HDCP-M组为27%（P <.05）。完全缓解情况不常见（HDCP组3%；HDCP-M组4%），仅在高剂量组中观察到。与HDCP组（38%）或HDCP-M组（34%）相比，SDCP组疾病进展更为频繁（57%）（P <.05）。然而，中位生存时间无显著差异（SDCP组6.9个月；HDCP组5.3个月；HDCP-M组7.2个月；P =.53）。高剂量组顺铂的平均实际剂量强度显著更高：HDCP组为41mg/m²/周，HDCP-M组为39mg/m²/周，而SDCP组为23mg/m²/周（P =.05）。与SDCP组相比，高剂量组耳毒性、呕吐和骨髓抑制的发生率增加，但肾毒性和神经病变程度相似。
本研究未证实达到的顺铂剂量强度下，NSCLC中顺铂存在陡峭的临床剂量-反应曲线。添加丝裂霉素可提高缓解率，但未改善生存率。有必要继续评估针对该疾病的新型药物。
