Weekly alternating therapy with irinotecan plus cisplatin and etoposide plus cisplatin in the treatment of patients with extensive small cell lung carcinoma

Abstract

BACKGROUND: Irinotecan has significant activity in small‐cell lung cancer (SCLC). The authors' previous phase 1 study of alternating weekly therapy with irinotecan/cisplatin (IP), etoposide/cisplatin (EP), and granulocyte–colony‐stimulating factor (G‐CSF) support was well tolerated and active in patients with SCLC. A phase 2 trial was conducted to estimate the efficacy of this regimen in previously untreated patients with extensive SCLC. METHODS: A total of 33 patients were treated between June 2002 and July 2007. Patients received 12 weeks of therapy with cisplatin (20 mg/m2) on Day 1 and irinotecan (100 mg/m2) on Day 1 and G‐CSF on Days 2 to 5 (Weeks 1, 3, 5, 7, 9, and 11) followed by cisplatin (20 mg/m2) on Day 1 and etoposide (60 mg/m2) on Days 1 to 3 with G‐CSF on Days 4 to 7 (Weeks 2, 4, 6, 8, 10, and 12). The primary endpoint was 1‐year survival rate. RESULTS: Grade 4 neutropenia (toxicities were determined using the National Cancer Institute Common Toxicity Criteria [version 2.0]) was noted in 5 (1.5%) of 343 courses with neutropenic fever in only 5 (1%) of 343 courses. One patient died of neutropenic sepsis. Nonhematologic toxicities grade ≥2 were observed in 15 (4%) of 343 courses and were limited to fatigue, hyponatremia, and diarrhea. The overall objective response rate was 89% in 28 assessable patients (no complete responses and 25 partial responses). The median progression‐free and overall survivals were 6.0 months and 10.9 months, respectively. The 1‐year survival rate was 33%. CONCLUSIONS: Weekly therapy with IP alternating with EP and G‐CSF support was well tolerated in patients with extensive SCLC, but did not demonstrate improved progression‐free or overall survival when compared with historical controls at the study institution. Cancer 2010. © 2010 American Cancer Society.