A dose escalation study of carboplatin and ifosfamide in advanced ovarian cancer

A dose escalation study of carboplatin (CBDCA) and ifosfamide was carried out in 35 patients with advanced ovarian carcinoma to determine the toxicity and therapeutic effect of this combination. In all, 13 patients had recurrent ovarian carcinoma, 11 had abdominal carcinomatosis of probable ovarian origin and 9 had newly diagnosed stage III/IV ovarian cancer. Myelosuppression was the major dose-limiting toxicity. At a dose of 400 mg/m2 CBDCA plus 5,000 mg/m2 ifosfamide, 61% of courses were associated with grade 3 leukopenia and 27%, with grade 3 thrombocytopenia. The lowest leukocyte and platelet counts occurred at a median of 14 days after treatment and cytopenia persisted for a median of 8 days. Myelotoxicity was cumulative with successive courses at this dose level, whereas at a dose of 400 mg/m2 CBDCA plus 4,000 mg/m2 ifosfamide it was possible to deliver the planned six courses of treatment. No other untoward toxicities were observed. A clinical response was achieved in 16/33 patients (49%), with 10 complete remissions (CRs), of which 3 were pathologically confirmed at laparotomy. No significant dose-response relationship was demonstrated in this heterogeneous group of patients. The predicted median duration of response is 12 months. CBDCA plus ifosfamide is an active combination therapy for ovarian cancer that merits further comparison with CBDCA alone. The recommended doses for six courses are 400 mg/m2 CBDCA plus 4,000 mg/m2 ifosfamide.