Objective: This phase I trial evaluated the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the proteasome inhibitor bortezomib when combined with carboplatin in ovarian cancer patients with recurrent and platinum- and taxane-resistant disease.
Methods: Patients with platinum- and taxane-resistant recurrent ovarian cancer, measurable disease, and a performance status of 0 to 2 were eligible. Bortezomib (0.8, 1.0, 1.3, or 1.5 mg/m2) was administered on days 1, 4, 8, and 11 by intravenous push with carboplatin (area under curve=5) on day 1; therapy was repeated every 28 days.
Results: Twenty-one women (median age, 63 years; range, 43 to 83 years) were treated with carboplatin and bortezomib at 0.8 mg/m2 (n=6), 1.0 mg/m2 (n=3), 1.3 mg/m2 (n=6), or 1.5 mg/m2 (n=6). At these levels, there were 1, 0, 1, and 3 DLTs, respectively, attributable to bortezomib; all were grade 3. The DLTs were fatigue (n=3); nausea, vomiting, and dehydration (n=1); and anorexia, dehydration, and syncope (n=1). Common grade 2 toxicities included fatigue (n=12), nausea (n=10), and anorexia, anemia, and dyspnea (n=7 each). The 18 patients evaluable for response all had stable disease (SD; n=8) or progressive disease (n=10). The median duration of SD was 4 months (range, 3 to 7 months). At the MTD of 1.3 mg/m2, 3 of 6 patients had SD.
Conclusions: The recommended dose of bortezomib in combination with carboplatin is 1.3 mg/m2. Treatment was reasonably well tolerated at the MTD.