A phase I study of paclitaxel, doxorubicin, and cisplatin in patients withpreviously 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 inclusio n of doxorubicin may have improved outcome. The purpose of this phase I stu dy 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 II or IV epithelial ovarian cancer were prim arily treated with escalating doses of doxorubicin in combination with pacl itaxel (135 mg/m(2) over 24 h) and cisplatin (75 mg/m(2)) every 3 weeks. Do xorubicin was started at 30 mg/m(2) and escalated by 10 mg/m(2) per treatme nt level. All patients received G-CSF support. Results. Eleven patients were treated at two dose levels. Dose limiting tox icity (DLT) was reached at the 40 mg/m(2) dose of doxorubicin. All patients experienced grade 4 neutropenia although none required hospitalization. DL T 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 comp lete clinical response (89%). Of the five patients undergoing second-look l aparotomy two were negative. Conclusions. The maximum tolerated dose of doxorubicin in this three-drug r egimen is 30 mg/m(2) with standard doses of paclitaxel and cisplatin. Hemat ologic toxicity is manageable using G-CSF. Doxorubicin appears to increase the renal toxicity of cisplatin which may be exaggerated by marked nausea a nd vomiting. This is an active but toxic regimen and alternative sequences and strategies should be evaluated. (C) 1998 Academic Press.