A RANDOMIZED PHASE-II STUDY OF IFOSFAMIDE MESNA/CISPLATIN PLUS G-CSF OR ETOPOSIDE/CISPLATIN PLUS G-CSF IN ADVANCED NON-SMALL-CELL LUNG-CANCER - A CANCER AND LEUKEMIA GROUP-B STUDY/

This Phase II study was designed to determine the efficacy of two chem otherapy regimens with G-CSF support for patients with advanced non-sm all cell lung cancer (NSCLC). One-hundred and one patients with Stage IIIB or IV NSCLC and performance status 0-1 were randomized to receive ifosfamide 2.0 g/m(2) days 1-3, mesna 400 mg/m(2) at 0, 4, 6 h days 1 -3, cisplatin 33 mg/m(2) days 1-3 or etoposide 200 mg/m(2) days 1-3, c isplatin 35 mg/m(2) days 1-3. Both groups received G-CSF 5 mu g/kg SQ day 4 to the post day 11 absolute neutrophil count > 10 000. For the 4 7 eligible patients receiving ifosfamide/mesna/cisplatin, the response rate was 26% (95% confidence interval: 14-40%) and the median surviva l 7.5 months (95% confidence interval: 5.8-11.0 months). Grade 3 or wo rse toxicities were: neutropenia 75%, thrombocytopenia 70%, infection 21%. There were two treatment-related deaths due to infection. For cou rse 1, the median absolute neutrophil count nadir was 1.3, platelet na dir 96 000 and incidence of febrile neutropenia 16%. For the 48 eligib le patients receiving etoposide/cisplatin, the response rate was 21% ( 95% confidence interval: 11-35%) and median survival 5.8 months (95% c onfidence interval: 4.5-9.7 months). Grade 3 or worse toxicities were: neutropenia 90%. thrombocytopenia 58%, infection 29%. There were thre e treatment-related deaths due to infection. For course 1, the median absolute neutrophil count was 0.2. platelet nadir 80 000 and incidence of Febrile neutropenia 33%. For both ifosfamide/mesna/cisplatin and e toposide/cisplatin. median duration of Grade IV neutropenia was short (less than or equal to 4 days), time to subsequent courses 21 days and dose delivered > 95% of planned dose. Although G-CSF allowed full dos es of drugs to be delivered on schedule, both ifosfamide/mesna/cisplat in and etoposide/cisplatin produced response rates and survival simila r to other cisplatin-based regimens. In view of the significant cost o f G-CSF and no obvious improvement in response rate, survival or toxic ity profile, G-CSF cannot be recommended with these chemotherapy regim ens for patients with advanced NSCLC.