Masuda N, Matsui K, Negoro S, Takifuji N, Takeda K, Yana T, Kobayashi M, Hirashima T, Kusunoki Y, Ushijima S, Kawase I, Tada T, Sawaguchi H, Fukuoka M
Department of Internal Medicine, Osaka Prefectural Habikino Hospital, Japan.
J Clin Oncol. 1998 Oct;16(10):3329-34. doi: 10.1200/JCO.1998.16.10.3329.
To determine the response rate, survival, and toxicity of irinotecan (CPT-11), a topoisomerase I inhibitor, combined with etoposide, a topoisomerase II inhibitor, in refractory or relapsed small-cell lung cancer (SCLC).
Twenty-five patients with refractory or relapsed SCLC were entered onto the trial. All 25 patients had been pretreated with some form of cisplatin-based combination chemotherapy and had also received previous etoposide- or anthracyclinecontaining chemotherapy. The median time off chemotherapy was 6.7 months (range, 0.9 to 23.5). Patients were treated at 4-week intervals using CPT-11 (a starting dose of 70 mg/m2 intravenously on days 1, 8, and 15) plus etoposide (80 mg/m2 intravenously on days 1 to 3), with a subsequent dose based on toxicity. In addition, recombinant human granulocyte colony-stimulating factor (rhG-CSF; 2 microg/kg/d) was given from day 4 to day 21, except on the days of CPT-11 administration.
All patients were assessable for toxicity and survival. Twenty-four patients were assessable for response. There were 14 partial responses (PRs) and three complete responses (CRs), for an overall response rate of 71% (95% confidence interval, 53% to 89%). The median response duration was 4.6 months. Median survival was 271 days. Major toxicities were myelosuppression (predominantly leukopenia) and diarrhea. Grade 3 to 4 neutropenia and thrombocytopenia occurred in 56% and 20% of patients, respectively. Grade 3 to 4 diarrhea was observed in 4%. There was one treatment-related death due to severe myelosuppression.
A combination of CPT-11 and etoposide with rhG-CSF support is an active therapy against refractory or relapsed SCLC and deserves to be studied more extensively in a phase III trial.
确定拓扑异构酶I抑制剂伊立替康（CPT-11）联合拓扑异构酶II抑制剂依托泊苷治疗难治性或复发性小细胞肺癌（SCLC）的缓解率、生存率及毒性。
25例难治性或复发性SCLC患者进入该试验。所有25例患者均接受过某种形式的含顺铂联合化疗，且之前也接受过含依托泊苷或蒽环类药物的化疗。化疗中断的中位时间为6.7个月（范围0.9至23.5个月）。患者每4周接受一次治疗，使用CPT-11（第1、8和15天静脉注射起始剂量70mg/m²）加依托泊苷（第1至3天静脉注射80mg/m²），后续剂量根据毒性调整。此外，除CPT-11给药日外，从第4天至第21天给予重组人粒细胞集落刺激因子（rhG-CSF；2μg/kg/d）。
所有患者均可评估毒性和生存情况。24例患者可评估缓解情况。有14例部分缓解（PR）和3例完全缓解（CR），总缓解率为71%（95%置信区间，53%至89%）。中位缓解持续时间为4.6个月。中位生存期为271天。主要毒性为骨髓抑制（主要是白细胞减少）和腹泻。3至4级中性粒细胞减少和血小板减少分别发生在56%和20%的患者中。观察到4%的患者出现3至4级腹泻。有1例因严重骨髓抑制导致的治疗相关死亡。
CPT-11与依托泊苷联合rhG-CSF支持是一种治疗难治性或复发性SCLC的有效疗法，值得在III期试验中更广泛地研究。
