CARBOPLATIN (CBDCA) HEXAMETHYLMELAMINE (HMM) ORAL ETOPOSIDE (VP-16) FIRST-LINE TREATMENT OF OVARIAN-CANCER PATIENTS WITH BULKY DISEASE - A PHASE-II STUDY

Hexamethylmelamine (HMM) and oral etoposide (VP-16) have shown to be a ctive against platinum-resistant epithelial ovarian cancer, On this ba sis a three-drug regimen including carboplatin (CBDCA) plus HMM and or al VP-16 was tested in previously untreated ovarian cancer patients wi th tumor size >2 cm, Since October 1991, 29 chemotherapy-naive ovarian cancer patients with tumor larger than 2 cm (20 stage III and 9 stage IV) have been treated for a total of 153 courses, CBDCA was administe red iv on Day 1. The dose was individualized using the Calvert formula (the target dose was AUC=5), VP-16 was administered orally at the dos e of 50 mg/m(2) Days 1-14, HMM at the dose of 150 mg/m(2) po Days 14-2 8. Therapy was repeated every 28 days for a total of 6 courses. In ord er to avoid severe leukopenia and delays in the treatment administrati on, G-CSF 5 mu g/kg/day sc Days 8-14 (or until postnadir recovery of n eutrophil count >10,000/mm(3)) and Days 22-28 was administered. All pa tients were evaluable for toxicity. No treatment-related deaths occurr ed, Myelotoxicity was the main side effect, It was grade 3-4 in a tota l of 13/29(45%) patients, One patient discontinued treatment after the first course due to HMM-related gastrointestinal toxicity, The actual delivered dose intensity was 89% of the planned dose, At the time of this analysis (April 1994) 26 patients are evaluable for response. Fif teen patients achieved a clinical complete remission and 9 a partial r esponse for a 92% overall response rate. Fourteen patients accepted se cond-look laparotomy. We observed 11 pathological complete regressions (42%; 95% CI, 21-63), At a median follow-up of 16 months 3 deaths hav e occurred, Only 2 patients with NED at second-look laparotomy have re lapsed. We stopped the accrual since the 95% confidence interval of th e pCR-rate observed exceeded 20%. This new first-line regimen seems to be highly effective in patients with poor-prognosis advanced ovarian cancer, although the data are not yet sufficiently mature for a final analysis of time to progression and overall survival. (C) 1999 Academi c Press, Inc.