Komaki R, Scott C, Ettinger D, Lee J S, Fossella F V, Curran W, Evans R F, Rubin P, Byhardt R W
The University of Texas M.D. Anderson Cancer Center, Department of Radiotherapy, Houston 77030, USA.
Int J Radiat Oncol Biol Phys. 1997 Apr 1;38(1):149-55. doi: 10.1016/s0360-3016(97)00251-4.
The purpose of this study was to compare the severity and distribution of the toxicities associated with the two different combinations of chemotherapy and radiotherapy.
This prospective randomized trial studied toxicities associated with induction chemotherapy followed by concurrent treatment (Arm 1) vs. immediate concurrent chemotherapy/radiotherapy (CT/RT) (Arm 2). Arm 1 consisted of vinblastine (VB), 5 mg/M2 I.V. bolus weekly, weeks 1-5 and cisplatin (DDP), 100 mg/M2 days 1 and 29, DDP 75 mg/M2, days 50, 71, and 92. Daily RT started on day 50; a total dose of 63 Gy was given in 34 fractions in 7 weeks. In Arm 2 RT started day 1; a total dose of 69.6 Gy was given in 58 fractions of 1.2 Gy bid, 5 days per week for 6 weeks with DDP 50 mg/M2 i.v. days 1 and 8, and oral VP-16 50 mg b.i.d. during the first 10 days of RT. DDP/VP-16 were repeated beginning day 29. Survival was used as the Phase II endpoint.
Between July 1992 and February 1994, 168 patients were randomized; 162 evaluable patients had minimum follow-up of 20 months. Eighty patients were registered to Arm 1 and 82 to Arm 2. Pretreatment characteristics were distributed evenly. Arm 1 had significantly more Grade 4 hematologic toxicity (62%) than Arm 2 (33%) (p = 0.021). Acute nonhematologic Grade 3+ toxicity was also greater (p = 0.018) in Arm 2 than Arm 1 due mainly to esophagitis (38 vs. 6%; p < 0.0001). Grade 3+ late esophageal toxicity was 12% on Arm 2 compared to 3% on Arm 1 (p = 0.006). There were no differences between the two arms in compliance with protocol specifications for either RT or CT. At 1 year, 31.7% of patients had in-field progression on Arm 1 compared to 19.8% on Arm 2 (p = 0.042), but overall progression-free survival rates were nearly identical; 50 and 49% for Arms I and II, respectively, at 12 months. One-year and median survivals were 65% and 15.5 months on Arm 1 compared to 58% and 14.4 months on Arm 2.
Whereas hematologic toxicity was greater in Arm 1, esophageal toxicity, both acute and late, was greater in Arm 2. Infield progression was lower in Arm 2, but overall progression rates were similar and there were no significant differences in survival between the two arms. A 3-arm randomized Phase III study is underway in the RTOG to compare sequential and concurrent CT/RT.
本研究旨在比较两种不同化疗与放疗联合方案相关毒性的严重程度及分布情况。
这项前瞻性随机试验研究了诱导化疗后序贯治疗（方案1）与即刻同步化疗/放疗（CT/RT）（方案2）相关的毒性。方案1包括长春碱（VB），5mg/M²静脉推注，每周1次，第1 - 5周；顺铂（DDP），第1天和第29天剂量为100mg/M²，第50、71和92天剂量为75mg/M²。每日放疗于第50天开始；7周内分34次给予总剂量63Gy。方案2放疗于第1天开始；每周5天，每天2次，每次1.2Gy，分58次给予总剂量69.6Gy，共6周，同时第1天和第8天静脉给予DDP 50mg/M²，放疗的前10天口服VP - 16 50mg，每日2次。DDP/VP - 16于第29天开始重复使用。生存情况作为II期研究终点。
1992年7月至1994年2月，168例患者被随机分组；162例可评估患者的最短随访时间为20个月。80例患者进入方案1，82例进入方案2。治疗前特征分布均匀。方案1的4级血液学毒性（62%）显著高于方案2（33%）（p = 0.021）。方案2的急性非血液学3级及以上毒性也高于方案1（p = 0.018），主要原因是食管炎（38%对6%；p < 0.0001）。方案2的3级及以上晚期食管毒性为12%，而方案1为3%（p = 0.006）。两组在放疗或化疗方案的依从性方面无差异。1年时，方案1中31.7%的患者出现野内进展，方案2为19.8%（p = 0.042），但总体无进展生存率相近；12个月时，方案I和方案II分别为50%和49%。方案1的1年生存率和中位生存期分别为65%和15.5个月，方案2分别为58%和14.4个月。
方案1的血液学毒性更大，而方案2的急慢性食管毒性更大。方案2的野内进展较低，但总体进展率相似，两组生存率无显著差异。放射肿瘤学组（RTOG）正在进行一项三臂随机III期研究，以比较序贯和同步CT/RT。
