Salvage treatment with topotecan in patients with irinotecan-refractory small cell lung cancer

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusions: 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.