A Phase I Study of Paclitaxel, Doxorubicin, and Cisplatin in Patients with Previously Untreated Epithelial Ovarian Cancer

Objective.Although doxorubicin is not currently popular as a primary agent in ovarian cancer, overviews of previous studies suggest that the inclusion of doxorubicin may have improved outcome. The purpose of this phase I study was to determine the maximal dose of doxorubicin that could be added to standard doses of paclitaxel and cisplatin with G-CSF support.Methods.Women with FIGO stage III or IV epithelial ovarian cancer were primarily treated with escalating doses of doxorubicin in combination with paclitaxel (135 mg/m²over 24 h) and cisplatin (75 mg/m²) every 3 weeks. Doxorubicin was started at 30 mg/m²and escalated by 10 mg/m²per treatment level. All patients received G-CSF support.Results.Eleven patients were treated at two dose levels. Dose limiting toxicity (DLT) was reached at the 40 mg/m²dose of doxorubicin. All patients experienced grade 4 neutropenia although none required hospitalization. DLT included renal toxicity and prolonged thrombocytopenia. Despite vigorous antiemetic regimens 60% of patients experienced severe nausea and vomiting. Nine patients were assessable for response. Eight patients have had a complete clinical response (89%). Of the five patients undergoing second-look laparotomy two were negative.Conclusions.The maximum tolerated dose of doxorubicin in this three-drug regimen is 30 mg/m²with standard doses of paclitaxel and cisplatin. Hematologic toxicity is manageable using G-CSF. Doxorubicin appears to increase the renal toxicity of cisplatin which may be exaggerated by marked nausea and vomiting. This is an active but toxic regimen and alternative sequences and strategies should be evaluated.