Park Se Hoon, Cho Eun Kyung, Kim Yujin, Kyung Sun Young, An Chang Hyeok, Lee Sang Pyo, Park Jeong Woong, Jeong Sung Hwan, Lee Jae-Ik, Choi Soo Jin, Park Jinny, Shin Dong Bok, Lee Jae Hoon
Department of Internal Medicine, Sungkyunkwan University Samsung Medical Center, Seoul, South Korea.
Cancer Chemother Pharmacol. 2008 Nov;62(6):1009-14. doi: 10.1007/s00280-008-0690-1. Epub 2008 Feb 8.
Although the efficacy of topotecan as a second-line chemotherapy for small-cell lung cancer (SCLC) has been consistently demonstrated in phase II/III clinical trials, the choice of irinotecan as the first-line therapy prevented the use of evidence-based option. This pilot study was conducted to determine the activity and safety of topotecan in SCLC patients refractory to first-line therapy with irinotecan and platinum.
Patients with primary refractory (no response, or progression during or < or =90 days after last chemotherapy) SCLC after treatment with a combination of irinotecan and platinum, received topotecan 1.5 mg/m(2) per day as a 30-min infusion daily for 5 days, every 3 weeks.
Of 17 eligible patients, ten patients were previously treated with irinotecan plus cisplatin and 7 were treated with irinotecan plus carboplatin. The median age was 68 years (range 44-75) and the median interval from the last chemotherapy was 50 days (range 21-89). A total of 33 chemotherapy cycles were delivered (median 2; range 1-5). All 17 patients discontinued therapy due to disease progression and 5 patients had progressive disease before second cycle. Toxic effects were mainly hematologic (grade > or =3 neutropenia in 65% of patients) and fatigue (grade 3 in 47%). In an intent-to-treat analysis, two (12%) patients had a confirmed partial response and two patients achieved stable disease. Median progression-free and overall survivals were 1.7 months (95% CI, 1.5-1.9) and 3.4 months (95% CI, 1.7-5.0), respectively.
Topotecan monotherapy for patients with irinotecan-refractory SCLC does not appear highly active but the observation of some responses merits further study in patients with chemosensitive disease.
尽管在II/III期临床试验中已持续证明拓扑替康作为小细胞肺癌（SCLC）二线化疗的疗效，但选择伊立替康作为一线治疗方案阻碍了基于证据的选择的应用。本前瞻性研究旨在确定拓扑替康在对伊立替康和铂类一线治疗难治的SCLC患者中的活性和安全性。
在用伊立替康和铂类联合治疗后出现原发性难治性（无反应，或在最后一次化疗期间或之后≤90天内进展）的SCLC患者，接受拓扑替康1.5mg/m²，每天30分钟静脉输注，共5天，每3周一次。
17例符合条件的患者中，10例先前接受过伊立替康加顺铂治疗，7例接受过伊立替康加卡铂治疗。中位年龄为68岁（范围44 - 75岁），距上次化疗的中位间隔为50天（范围21 - 89天）。共进行了33个化疗周期（中位值2；范围1 - 5）。所有17例患者均因疾病进展而停止治疗，5例患者在第二个周期前出现疾病进展。毒性作用主要为血液学毒性（65%的患者出现≥3级中性粒细胞减少）和疲劳（47%的患者为3级）。在意向性分析中，2例（12%）患者确认部分缓解，2例患者病情稳定。无进展生存期和总生存期的中位值分别为1.7个月（95%CI，1.5 - 1.9）和3.4个月（95%CI，1.7 - 5.0）。
拓扑替康单药治疗对伊立替康难治的SCLC患者似乎活性不高，但观察到的一些反应值得对化疗敏感疾病患者进行进一步研究。
