A phase I study of a daily x3 schedule of intravenous vinorelbine for refractory epithelial ovarian cancer

Purpose. To determine the toxicity and activity of intravenous vinorelbine given daily for 3 consecutive days every 3 weeks in patients with platinum-resistant epithelial ovarian cancer. Patients and methods. Between September 1994 and October 1995, 23 women with refractory epithelial ovarian cancer were entered onto this phase I study. All patients had measurable disease and platinum-resistant tumor, and prior therapy was limited to a maximum of two prior regimens. Nineteen (83%) were assessable for toxicity and 20 (87%) were assessable for response. Vinorelbine was administered intravenously daily for 3 consecutive days; this was repeated every 21 days. The starting dose was 20 mg/m(2) daily x3, with dose escalation by 5 mg/m(2) daily x3. Dose-limiting toxicity (DLT) was defined as grade 4 granulocytopenia for >3 days, grade 4 thrombocytopenia, neutropenic fever, or grade 3 or greater nonhematologic toxicity. The maximal tolerated dose (MTD) was defined as the highest dose level at which <50% of patients developed a DLT, Once the MTD of vinorelbine without granulocyte colony-stimulating factor (filgrastim) support was defined, dosing was begun at the MTD level and administration of 5 mu g/kg filgrastim was initiated on day 4 and continued until WBC counts reached >10,000/mu L. Clinical response, progression-free survival, and survival were also determined. Results. Nineteen patients evaluable for toxicity received a total of 135 cycles of vinorelbine, The major DLT was neutropenia. The MTD of vinorelbine without filgrastim support was established as 20 mg/m(2) daily x3. The MTD of vinorelbine with filgrastim support was established as 25 mg/m(2) daily x3. Of 20 patients evaluable for response, 2 patients (10%) had a complete response and 4 (20%) had a partial response, for an overall response rate of 30%, Conclusion. These results warrant further study of vinorelbine in patients with platinum-resistant epithelial ovarian cancer. However, further study of the daily x3 schedule may not be warranted because of failure to achieve higher weekly dose intensity and because of nonhematologic toxicity in the form of intense bone pain, (C) 1998 Academic Press.