PHASE-I-II STUDY OF 2 CONSECUTIVE COURSES OF HIGH-DOSE EPIPODOPHYLLOTOXIN, IFOSFAMIDE, AND CARBOPLATIN WITH AUTOLOGOUS BONE-MARROW TRANSPLANTATION FOR TREATMENT OF ADULT PATIENTS WITH SOLID TUMORS

We describe a phase I-II study of two consecutive 5-day courses of a three-drug regimen of ifosfamide (IFM), carboplatin (CBDCA), and either etoposide (VP-16) (regimen 1) or teniposide (VM-26) (regimen 2) in high doses together with autologous bone marrow transplantation (ABMT), for previously treated patients with ovarian carcinoma (OC), germ cell tumors (GCT), gestational trophoblastic disease (GTD), or oat cell carcinoma (OCC). Forty-four patients entered the study. Two patients with OC received regimen 1, and 22 were given regimen 2. Sixteen patients with GCT, two with GTD, and two with OCC were treated with regimen 1. Six patients (13%) died of toxicity. Nephropathy and esophagitis were the dose-limiting toxic effects. The maximum-tolerated doses (MTDs) were 1,500 and 200 mg/m2/d for 5 days for IFM and CBDCA, respectively, in combination with VP-16 250 mg/m2/d for 5 days (regimen 1), and 150, 1,500, and 200 mg/m2/d for 5 days for VM-26, IFM, and CBDCA, respectively (regimen 2). The response rate of patients with OC was 78% (complete response [CR], 14%). For patients previously resistant to chemotherapy, the response rate was 70%. There were no long-term disease-free survivors among patients with OC. The response rate of patients with GCT was 60% (CR, 33%). All responders with GCT were resistant to previous chemotherapy. Unmaintained CRs lasted 2, 6, 8 + , 27+, and 37 + months. Of the two patients with GTD, one with previous resistance to chemotherapy attained a CR of 18+ months. One patient with OCC attained a CR lasting 6 months. The regimen possesses great antitumor activity. It produced CRs of long duration in a number of patients with GCT and GTD who were previously resistant to chemotherapy.