Kubota Kaoru, Nishiwaki Yutaka, Sugiura Takahiko, Noda Kazumasa, Mori Kiyoshi, Kawahara Masaaki, Negoro Shunichi, Watanabe Koshiro, Imamura Fumio, Tamura Tomohide, Saijo Nagahiro
National Cancer Center Hospital East, Kashiwa, Japan.
Clin Cancer Res. 2005 Aug 1;11(15):5534-8. doi: 10.1158/1078-0432.CCR-04-1771.
Irinotecan and cisplatin (IP) significantly improved survival compared with etoposide and cisplatin (EP), in patients with extensive-stage small cell lung cancer (SCLC) in a previous Japan Clinical Oncology Group (JCOG) randomized trial. JCOG9903 was conducted to evaluate the safety of sequentially given IP following concurrent EP plus twice-daily thoracic irradiation (TRT) for the treatment of limited-stage SCLC (LSCLC).
Between October 1999 and July 2000, 31 patients were accrued from 10 institutions. Thirty patients were assessable for toxicity, response, and survival. Treatment consisted of etoposide 100 mg/m(2) on days 1 to 3, cisplatin 80 mg/m(2) on day 1, and concurrent twice-daily TRT of 45 Gy beginning on day 2. The IP regimen started on day 29 and consisted of irinotecan 60 mg/m(2) on days 1, 8, and 15 and cisplatin 60 mg/m(2) on day 1, with three 28-day cycles.
There were no treatment-related deaths. The response rate was 97% (complete response, 37%; partial response, 60%). Median overall survival was 20.2 months; 1-, 2-, and 3-year survival rates were 76%, 41%, and 38%, respectively. Of the 24 patients who started the IP regimen, 22 received two or more cycles. Hematologic toxicities of grade 3 or 4 included neutropenia (67%), anemia (50%), and thrombocytopenia (4%). Nonhematologic toxicities of grade 3 or 4 included diarrhea (8%), vomiting (8%), and febrile neutropenia (8%). Of the 20 patients with recurrence, none had local recurrence alone and only two had both local and distant metastasis as the initial sites of disease progression.
IP following concurrent EP plus twice-daily TRT is safe with acceptable toxicities. A randomized phase III trial comparing EP with IP following EP plus concurrent TRT for LSCLC is ongoing (JCOG0202).
在先前一项日本临床肿瘤学组（JCOG）的随机试验中，与依托泊苷和顺铂（EP）相比，伊立替康和顺铂（IP）显著提高了广泛期小细胞肺癌（SCLC）患者的生存率。开展JCOG9903试验以评估在同步EP加每日两次胸部放疗（TRT）治疗局限期SCLC（LSCLC）后序贯给予IP的安全性。
1999年10月至2000年7月期间，从10个机构招募了31例患者。30例患者可评估毒性、反应和生存情况。治疗方案包括第1至3天给予依托泊苷100mg/m²，第1天给予顺铂80mg/m²，并于第2天开始同步每日两次45Gy的TRT。IP方案于第29天开始，包括第1、8和15天给予伊立替康60mg/m²，第1天给予顺铂60mg/m²，共三个28天周期。
无治疗相关死亡。缓解率为97%（完全缓解，37%；部分缓解，60%）。中位总生存期为20.2个月；1年、2年和3年生存率分别为76%、41%和38%。在开始IP方案的24例患者中，22例接受了两个或更多周期的治疗。3级或4级血液学毒性包括中性粒细胞减少（67%）、贫血（50%）和血小板减少（4%）。3级或4级非血液学毒性包括腹泻（8%）、呕吐（8%）和发热性中性粒细胞减少（8%）。在20例复发患者中，无单独局部复发者，仅2例以局部和远处转移作为疾病进展的初始部位。
同步EP加每日两次TRT后序贯给予IP是安全的，毒性可接受。一项比较EP与EP加同步TRT后IP治疗LSCLC的随机III期试验正在进行（JCOG0202）。
