Locoregionally advanced carcinoma of the oropharynx: Conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy - A multicenter randomized trial
Locoregionally advanced carcinoma of the oropharynx: Conventional radiotherapy vs. accelerated hyperfractionated radiotherapy vs. concomitant radiotherapy and chemotherapy - A multicenter randomized trial
复制标题
DOI：
10.1016/s0360-3016(02)03792-6
复制
发表时间：
2003-01-01
影响因子：
7
通讯作者：
Marsoni, S
中科院分区：
文献类型：
--
作者：
Olmi, P;Crispino, S;Marsoni, S
目的：比较A组常规分割放疗（RT）与B组分程加速超分割放疗（S-AHF）与C组常规分割放疗加同期化疗（CT）治疗晚期、不可切除的口咽部表皮样肿瘤的生存率和毒性。方法和材料：在1993年1月至1998年6月期间，192例既往未经治疗的III期和IV期口咽癌（不包括T1 N1和T2 N1）患者参加了一项多中心、随机III期试验（ORO 93-01）。对于A组和C组，66-70戈伊，分33-35次，每周5天，在6.5-7周内对肿瘤和阳性淋巴结给药。在B组中，递送至肿瘤和受累淋巴结的剂量为64-67.2戈伊，每天给予2次，每次1.6戈伊，每次间隔至少4 h，优选6 h，每周5天。在38.4戈伊剂量下，计划进行2周分割;分割后，以相同方式恢复RT。C组采用卡铂和5-氟尿嘧啶联合化疗方案（CBDCA 75 mg/m（2），第1-4天; 5-FU 1，000 mg/m（2）i. v.超过96小时，第1-4天，每28天循环一次结果：两组总生存期比较差异无统计学意义（P> 0.05），两组间比较差异无统计学意义（P> 0.05（p = 0.129）：24个月时，A组40%、B组37%、C组51%存活。同样，无事件生存期方面无统计学显著差异（p = 0.196）：24个月时A组20%、B组19%和C组37%的无事件生存期。相反，3组间的2年无病生存率存在显著差异（P = 0.022），C组具有优势。24个月时，C组中无复发的患者比例为42%，A组为23%，B组为20%。A组患者发生G3+急性粘膜炎的频率低于B或C组患者（14.7% vs. 40.3% vs. 44%）。关于CT相关急性毒性，除1例致死性肾毒性外，仅观察到血液学G3+（3级或以上）急性后遗症（世界卫生组织量表），最常见的是白细胞减少症（22.7%）。C组显示G3+皮肤略多，s.c.组织和粘膜晚期副作用（RTOG量表），尽管严重后遗症相对罕见，粘膜后遗症最常见的是短暂的。所有三个治疗组中持续性G3口干症的发生率相当。结论：对于晚期口咽鳞状细胞癌，同步CT和RT与本试验方案相结合比单独RT更好，可以提高无病生存率。然而，这种改善并没有转化为总体生存率的改善，而是与较高的急性发病率相关。(C)2003年爱思唯尔科学公司
Purpose: To compare conventional fractionation radiation therapy (RT), Arm A, vs. split-course accelerated hyperfractionated RT (S-AHF), Arm B, vs. conventional fractionation RT plus concomitant chemotherapy (CT), Arm C, in terms of survival and toxicity for advanced, unresectable epidermoid tumors of oropharynx.Methods and Materials: Between January 1993 and June 1998, 192 previously untreated patients affected with Stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were accrued in a multicenter, randomized Phase III trial (ORO 93-01). For Arms A and C, 66-70 Gy in 33-35 fractions, 5 days a week, were administered in 6.5-7 weeks to tumor and positive nodes. In Arm B, the dose delivered to tumor and involved nodes was 64-67.2 Gy, giving 2 fractions of 1.6 Gy every day with an interfraction interval of at least 4 h and preferably 6 h, 5 days a week. At 38.4 Gy, a 2-week split was planned; after the split, RT was resumed with the same modality. In Arm C, CT regimen consisted of carboplatin and 5-fluorouracil (CBDCA 75 mg/m(2), Days 1-4; 5-FU 1,000 mg/m(2) i.v. over 96 h, Days 1-4, recycling every 28 days (at 1st, 5th, and 9th week).Results: No statistically significant difference was detected in overall survival (p = 0.129): 40% Arm A vs. 37% Arm B vs. 51 % Arm C were alive at 24 months. Similarly, there was no statistically significant difference in terms of event-free survival (p = 0.196): 20% for Arm A, 19% for Arm B, and 37% for Arm C were event free at 24 months. On the contrary, the 2-year disease-free survival was significantly different among the three arms (P = 0.022), with a superiority for Arm C. At 24 months, the proportion of patients without relapse was 42% for Arm C vs. 23 % for Arm A and 20 % for Arm B. Patients in Arm A less frequently developed G3+ acute mucositis than their counterparts in Arm B or C (14.7% vs. 40.3% vs. 44%). Regarding the CT-related acute toxicity, apart from I case of fatal nephrotoxicity, only hematologic G3+ (Grade 3 or higher) acute sequelae were observed (World Health Organization scale), most commonly leukopenia (22.7%). Arm C showed slightly more G3+ skin, s.c. tissue, and mucosal late side effects (RTOG scale), although significant sequelae were relatively uncommon, and mucosal sequelae were most commonly transient. The occurrence of persistent G3 xerostomia was comparable in all three treatment arms.Conclusions: The combination of simultaneous CT and RT with the regimen of this trial is better than RT alone in advanced oropharyngeal squamous-cell carcinomas, by increasing disease-free survival. This improvement, however, did not translate into an overall survival improvement, and was associated with a higher incidence of acute morbidity. (C) 2003 Elsevier Science Inc.