Long-term results and pharmacokinetics of high-dose paclitaxel in patientswith refractory epithelial ovarian carcinoma

The purpose of this study was to analyze the efficacy and toxicity of a hig h dose of paclitaxel in patients with ovarian cancer refractory to platinum chemotherapy. Another phase II study of hydroxyurea was run in the same pa tient population. Fifty patients with measurable ovarian cancer were entere d on this phase II study at The University of Texas M. D. Anderson Cancer C enter. Treatment consisted of 250 mg/m(2) of paclitaxel given by continuous intravenous infusion over 24 h every 3 weeks. Patients with disease unresp onsive to paclitaxel could then be crossed over to hydroxyurea, and vice ve rsa. Twenty-five (53%) out of 47 evaluable patients had a response (two complete responses and 23 partial responses). Twelve (26%) patients had stable dise ase. The median survival was 11.3 months. The main toxic effect was neutrop enia (98% of patients) with 28 (9%) episodes of neutropenic fever. Neutrope nia required therapy with granulocyte colony-stimulating factor. Other side effects were alopecia (100%), anemia (98%), gastrointestinal problems (57% ), stomatitis (27%), and neurotoxicity (55%). Paclitaxel administered at a high dose as a single agent proved to be very active in patients who had platinum-refractory ovarian cancer and was well tolerated. Further studies of high-dose paclitaxel in patients with ovarian carcinoma are indicated.