Phase II study of ifosfamide, carboplatin, and oral etoposide chemotherapy for extensive-disease small-cell lung cancer: An Eastern Cooperative Oncology Group pilot study

Purpose: A phase II study of ifosfamide, carboplatin, and prolonged oral administration of etoposide (ICE) in patients with untreated extensive- disease (ED) small-cell lung cancer (SCLC) was conducted to assess toxicities, response, and median survival. Patients and Methods: Between July 1990 and August 1992, 35 patients were treated. ICE doses were ifosfamide 5 g/m² by 24-hour continuous intravenous (CIV) infusion with mesna on day 1, carboplatin 300 mg/m² intravenously (IV) on day 1, and etoposide 50 mg/m² orally on days 1 to 21 every 4 weeks for up to six to eight cycles (schedule I). Because of severe hematologic toxicity in the first 18 patients, the last 17 patients received ifosfamide 3.75 mg/m² IV on day 1, carboplatin 300 mg/m² IV on day 1, and etoposide 50 mg orally on days 1 to 14 (schedule II). Results: Nine of 18 patients (50%) on schedule I had 13 episodes of severe hematologic toxicity (one death), and only two (11%) received full doses on cycle 2. However, with schedule II, only four of 17 patients (24%) developed severe hematologic toxicity, and eight (47%) received full doses on cycle 2. Objective responses were observed in 29 of 35 patients (83%) (schedule I, 16 of 18 patients [89%]; schedule II, 13 of 17 patients [76%]). There were eight (23%) complete responses (CRs) and 21 (60%) partial responses (PRs). The median survival duration was 8.3 months, and 1- and 2-year survival rates were 37% and 14%, respectively. Conclusion: ICE with oral etoposide has comparable activity with other regimens in ED SCLC. However, the 2-year survival rate may be higher and ICE with the lower doses of schedule II could be given safely with acceptable toxicity. Further studies of ICE compared with standard two-drug regimens are warranted.