High-dose versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin in suboptimal ovarian cancer: a randomized study of the Gruppo Oncologico Nord-Ovest.

The aim of the study was to compare high-versus low-dose cisplatin in combination with cyclophosphamide and epidoxorubicin as primary chemotherapy for suboptimal stage III and IV ovarian cancer.One hundred forty-five patients were randomized to receive six courses of cisplatin 50 or 100 mg/m2 plus epidoxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2. The two treatment arms were well balanced; all patients had greater than 2 cm and 37.2\% had greater than 5 cm of residual disease; 29.6\% had stage IV disease.Patients in the high-dose arm received a double dose-intensity and double total dose of cisplatin. The high-dose regimen induced significantly more episodes of leukopenia (47.8\% v 32.8\%, P = .05), thrombocytopenia (21.7\% v 3.2\%, P = .003), anemia (37.6\% v 12.5\%, P = .002), nephrotoxicity (six v one patient), and neurotoxicity (30.4\% v 6.3\%, P = .002). There were no significant differences in efficacy in terms of clinical response rate (high-dose 57.5\% v low-dose 61.1\%), pathologic complete response (CR) (9.6\% v 18.1\%), median survival times (29 v 24 months), and median progression-free survival (18 v 13 months).This study shows that doubling the dose-intensity and total dose of cisplatin in combination with epidoxorubicin and cyclophosphamide has significant toxic effects and does not improve clinical outcome in patients with suboptimal ovarian cancer.