Schaefer Paul L, Marks Randolph S, Mahoney Michelle R, Sloan Jeff A, Bauman Mitchell D, Tazelaar Henry D, Kugler John W, Mailliard James A, Ebbert Larry P, Wiesenfeld Martin
Toledo Community Hospital Oncology Program CCOP, Toledo, Ohio, USA.
Am J Clin Oncol. 2003 Jun;26(3):236-40. doi: 10.1097/01.COC.0000018038.28645.46.
A randomized two-stage, phase II study was conducted to assess the antitumor activity of two different schedules of topotecan in the treatment of extensive-stage small-cell lung cancer (SCLC) in chemotherapy-naive patients. A total of 40 eligible patients were randomized to receive either the daily schedule, with topotecan being administered intravenously at 1.5 mg/m2 daily for 5 days every 3 weeks, or the continuous-infusion schedule, with topotecan administered intravenously at a dosage of 1.3 mg/m2 per day over 72 hours every 4 weeks. Randomization to the continuous-infusion schedule was discontinued due to inactivity, and an additional 20 patients were treated on the daily schedule. Patients received an average of 5 courses (range: 1-13) of the daily schedule compared to an average of 2 courses (range: 1-7) of the continuous-infusion schedule (p < 0.01). Confirmed response rates for the daily and continuous-infusion schedules are 62.5% (90% CI: 49-75%) and 15% (90% CI: 1-29%), respectively. Toxicity was predominantly hematologic with 92% (55/60) having greater than or equal to grade III neutropenia and 58% (35/60) reporting greater than or equal to grade III leukopenia for both IV schedules. Nonhematologic toxicity was very mild, with only 10% (6/60) patients experiencing grade IV toxicities. One patient died of infection on the continuous-infusion arm. Median times to progression for the daily and continuous-infusion schedules are 5 months (90% CI: 4.4-7.2) and 2 months (90% CI: 1.1-2.1), respectively. Estimated 1-year survival rates for patients receiving daily and continuous-infusion schedules are 63% (90% CI: 51-76%) and 55% (90% CI: 39-77%), respectively. Fifty percent (30/60) of patients received second-line therapy with etoposide and cisplatin. Forty-three percent (13/30) of patients who received second-line therapy achieved a confirmed response. Topotecan showed significant activity in the treatment of extensive stage SCLC when administered as a brief daily IV repeated every 3 weeks.
开展了一项随机两阶段II期研究，以评估两种不同拓扑替康给药方案对初治广泛期小细胞肺癌（SCLC）患者的抗肿瘤活性。总共40例符合条件的患者被随机分组，分别接受每日给药方案（拓扑替康以1.5mg/m²静脉注射，每日1次，共5天，每3周重复）或持续静脉输注给药方案（拓扑替康以1.3mg/m²/天的剂量静脉输注72小时，每4周重复）。由于无效，持续静脉输注给药方案的随机分组停止，另外20例患者接受每日给药方案治疗。每日给药方案的患者平均接受5个疗程（范围：1 - 13个疗程），而持续静脉输注给药方案的患者平均接受2个疗程（范围：1 - 7个疗程）（p<0.01）。每日给药方案和持续静脉输注给药方案的确认缓解率分别为62.5%（90%CI：49 - 75%）和15%（90%CI：1 - 29%）。两种静脉给药方案的毒性主要为血液学毒性，92%（55/60）的患者出现≥III级中性粒细胞减少，58%（35/60）的患者报告有≥III级白细胞减少。非血液学毒性非常轻微，只有10%（6/60）的患者出现IV级毒性。持续静脉输注组有1例患者死于感染。每日给药方案和持续静脉输注给药方案的中位进展时间分别为5个月（90%CI：4.4 - 7.2）和2个月（90%CI：1.1 - 2.1）。接受每日给药方案和持续静脉输注给药方案患者的估计1年生存率分别为63%（90%CI：51 - 76%）和55%（90%CI：39 - 77%）。50%（30/60）的患者接受了依托泊苷和顺铂的二线治疗。接受二线治疗的患者中有43%（13/30）获得了确认缓解。拓扑替康每3周静脉注射1次，短暂每日给药时，在广泛期SCLC治疗中显示出显著活性。
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