Phase I trial of the proteasome inhibitor bortezomib in combination with carboplatin in patients with platinum- and taxane-resistant ovarian cancer.
Gynecol Oncol. 2007 Sep 28
Ramirez PT, Landen CN Jr, Coleman RL, Milam MR, Levenback C, Johnston TA, Gershenson DM.
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, PO Box 301439, Houston, TX 77230-1439, USA.
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/m(2)) 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/m(2) (n=6), 1.0 mg/m(2) (n=3), 1.3 mg/m(2) (n=6), or 1.5 mg/m(2) (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/m(2), 3 of 6 patients had SD.
CONCLUSIONS.: The recommended dose of bortezomib in combination with carboplatin is 1.3 mg/m(2). Treatment was reasonably well tolerated at the MTD. |
