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

• Published in: Gynecologic oncology 1998-09, Vol.70 (3), p.404-409
• Main Authors: GERSHENSON, D. M, BURKE, T. W, MORRIS, M, BAST, R. C, GUASPARI, A, HOHNEKER, J, WHARTON, J. T
• Format: Article
• Language: English
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Agents, Phytogenic - adverse effects; Biological and medical sciences; Carcinoma - drug therapy; Chemotherapy; Disease-Free Survival; Drug Administration Schedule; Drug Resistance, Neoplasm; Female; Humans; Injections, Intravenous; Medical sciences; Middle Aged; Ovarian Neoplasms - drug therapy; Patient Selection; Pharmacology. Drug treatments; Treatment Outcome; Vinblastine - administration & dosage; Vinblastine - adverse effects; Vinblastine - analogs & derivatives
• ISSN: 0090-8258; 1095-6859
• DOI: 10.1006/gyno.1998.5130

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. 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/m2 daily x3, with dose escalation by 5 mg/m2 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 10,000/microL. Clinical response, progression-free survival, and survival were also determined. 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/m2 daily x3. The MTD of vinorelbine with filgrastim support was established as 25 mg/m2 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%. 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.