Byhardt R W, Scott C B, Ettinger D S, Curran W J, Doggett R L, Coughlin C, Scarantino C, Rotman M, Emami B
Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee 53226, USA.
Cancer. 1995 May 1;75(9):2337-44. doi: 10.1002/1097-0142(19950501)75:9<2337::aid-cncr2820750924>3.0.co;2-k.
Clinical trials of hyperfractionated radiation therapy and induction chemotherapy followed by standard radiation therapy have shown improved survival in patients with unresectable nonsmall cell lung cancer (NSCLC). Radiosensitization may improve local tumor control when chemotherapy is given concurrently with hyperfractionated radiation therapy, but also may increase toxicity. A Phase I/II trial, Radiation Therapy Oncology Group 90-15, was designed to evaluate whether this strategy could improve survival with acceptable toxicity and be part of a Phase III trial of chemoradiation sequencing.
Vinblastine (5 mg/M2 weekly x 5 weeks) and cisplatin (75 mg/M2 days 1, 29, and 50) were given during twice-daily irradiation (1.2 Gy, 6 hours apart) to 69.6 Gy in 58 fractions in 6 weeks. Eligible patients had American Joint Committee on Cancer (AJCC) Stage II (unresected) or IIIA-B NSCLC and Karnofsky performance status 70 or greater; there were no weight loss restrictions.
Of 42 eligible patients, 76% had greater than 5% weight loss, 45% had T4 primary tumors, and 62% were Stage IIIB. All protocol treatment was completed in 53%. Acute toxicity was predominantly hematologic with 19 of 42 (45%) having Grade 4 toxicity or higher, three (7%) with septic death. Ten of 42 (24%) had Grade 3 or higher esophagitis. There were two (4.7%) patients with Grade 3 or higher (1 lung and 1 esophagus) and two (4.7%) with Grade 4 or higher (1 lung and 1 hematologic) late toxicities. Median survival time was 12.2 months, with an overall 1-year survival of 54%, an estimated 2 year survival of 28% and a 1-year progression free survival of 38%.
For patients with unresectable nonsmall cell lung cancer, who were not selected on the basis of weight loss, concurrent hyperfractionated irradiation and chemotherapy had more intense acute toxicity than hyperfractionation alone, but late toxicity was acceptable. One and 2-year survival rates were 54 and 28%, respectively.
超分割放射治疗联合诱导化疗后行标准放射治疗的临床试验表明，不可切除的非小细胞肺癌（NSCLC）患者的生存率有所提高。当化疗与超分割放射治疗同时进行时，放射增敏作用可能会改善局部肿瘤控制，但也可能增加毒性。一项I/II期试验，放射肿瘤学组90-15，旨在评估该策略是否能在可接受的毒性下提高生存率，并成为放化疗顺序的III期试验的一部分。
在每日两次照射（1.2 Gy，间隔6小时）期间给予长春碱（5 mg/M2每周×5周）和顺铂（75 mg/M2第1、29和50天），6周内分58次给予69.6 Gy。符合条件的患者患有美国癌症联合委员会（AJCC）II期（未切除）或IIIA-B期NSCLC，卡诺夫斯基功能状态为70或更高；无体重减轻限制。
42例符合条件的患者中，76%体重减轻超过5%，45%有T4原发性肿瘤，62%为IIIB期。53%的患者完成了所有方案治疗。急性毒性主要为血液学毒性，42例中有19例（45%）出现4级或更高毒性，3例（7%）因败血症死亡。42例中有10例（24%）出现3级或更高的食管炎。有2例（4.7%）患者出现3级或更高（1例肺部和1例食管）和2例（4.7%）出现4级或更高（1例肺部和1例血液学）的晚期毒性。中位生存时间为12.2个月，1年总生存率为54%，估计2年生存率为28%，1年无进展生存率为38%。
对于未根据体重减轻情况进行选择的不可切除非小细胞肺癌患者，同步超分割照射和化疗的急性毒性比单纯超分割更强烈，但晚期毒性是可接受的。1年和2年生存率分别为54%和28%。
