Phase II study of ifosfamide, carboplatin, etoposide and GM-CSF in small cell lung cancer

Twenty patients with small cell lung cancer (SCLC) were entered to the study. Fourteen cases were male and six cases were female. Twelve cases were extensive disease, eight cases were limited disease. Median age was 60 years (range = 40-72 years), median performance status was 70 per cent (range = 60-80%). All patients were treated with combination chemotherapy consisting of ifosfamide 5 g/m2 intravenous infusion over 4 hours with mesna uroprotection, carboplatin 300 mg/m2 intravenous infusion over 2 hours on day 1, and etoposide 120 mg/m2 intravenous infusion over 4 hours on day 1-3. Chemotherapy was re-cycled every 28 days. Assessment of hematologic toxicity (CBC) was performed two times per week. If there was grade 3 or 4 neutropenia on any cycle of chemotherapy, GM-CSF was administered for febrile neutropenia and on the next cycle it was administered prophylactically on day 4-14.

Seventeen cases were evaluable for response and toxicity (three cases were inevaluable due to loss to follow-up after the first cycle of chemotherapy). Fourteen cases (five limited disease, nine extensive disease) achieved partial response (82.5%). Two cases had stable disease, one case died on day 7. One year survival was 23.5 per cent. Seventy and a half percent grade 3 and 4 neutropenia was seen during the first cycle. One patient had febrile neutropenia. After being prophylactically treated with GM-CSF, grade 3 and 4 neutropenia was reduced from 70.5 per cent to 56.2 per cent, 46.7 per cent, 63.6 per cent, 42.8 per cent and 0 per cent in cycle 2-6 respectively. Major toxicity of GM-CSF consisted of transient chest distress, chills, sweating and hypotension which subsided in 5-10 minutes. No fever or skin rash was observed.

Combination of ifosfamide, carboplatin and etoposide (ICE) is an active regimen for small cell lung cancer. However, because of its severe myelosuppression, this regimen needs hematopoietic growth factor support, and GM-CSF was used in this study. The administration of GM-CSF rendered ICE chemotherapy to be given safely.