CISPLATIN, IFOSFAMIDE, AND PROLONGED ORAL ETOPOSIDE IN THE TREATMENT OF PATIENTS WITH EXTENSIVE SMALL-CELL LUNG-CARCINOMA

BACKGROUND. The combination of cisplatin, ifosfamide, and prolonged or al etoposide (PIE) was studied in patients with extensive small cell l ung carcinoma (SCLC) in a Phase I trial followed by a Phase II trial t o determine the maximum tolerated dose (MTD), characterize toxicity, a nd estimate response and median survival rates. METHODS. Thirty-three patients were treated between October 1991 and December 1994. Doses fo r the initial cohort were cisplatin 20 mg/m(2)/day, ifosfamide 1500 mg /m(2)/day with mesna (all given intravenously on Days 1-3), and oral e toposide 50 mg/m(2) on Days 4-17. This cycle was repeated every 4 week s for up to 6 cycles. The MTD was reached for the first 9 patients. Fo r these 9 patients and the next 24 patients, who were entered in the P hase II trial, response and survival were estimated. RESULTS. Dose-lim iting toxicity was manifested as Grade 4 neutropenia in 3 of 3 patient s (associated with fever in 2 of 3), and Grade 4 thrombocytopenia was encountered in 2 of 3 patients at the second dose level. Of 6 patients treated at the first dose level, 4 achieved targeted myelosuppression (absolute granulocyte count nadir <1000), but only 1 experienced Grad e 4 neutropenia, defining this level as the MTD. Grade 4 neutropenia a nd/or thrombocytopenia was observed in 36 (24%) of a total of 152 cour ses administered at or below the MTD. Nonhematologic toxicity above Gr ade 2 was uncommon, excluding nausea and vomiting. Overall objective r esponse rate was 93% of 30 evaluable patients: 5 (17%) complete respon ses and 23 partial responses (76%). Median failure free and overall su rvival durations were 36 and 54 weeks, respectively. CONCLUSIONS. The combination of cisplatin, ifosfamide, and oral etoposide produced enco uraging failure free and overall median survival rates in patients wit h extensive SCLC. These results warrant further evaluation of this reg imen in the initial therapy of patients with limited stage disease. (C ) 1998 American Cancer Society.