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.
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 cancerpatients 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.
Authors: Danielle A Jandial; William E Brady; Stephen B Howell; Heather A Lankes; Russell J Schilder; Jan H Beumer; Susan M Christner; Sandra Strychor; Matthew A Powell; Andrea R Hagemann; Kathleen N Moore; Joan L Walker; Paul A DiSilvestro; Linda R Duska; Paula M Fracasso; Don S Dizon Journal: Gynecol Oncol Date: 2017-03-22 Impact factor: 5.482
Authors: Isa N Cruz; Helen M Coley; Holger B Kramer; Thumuluru Kavitah Madhuri; Nur A M Safuwan; Ana Rita Angelino; Min Yang Journal: Cancer Genomics Proteomics Date: 2017-01-02 Impact factor: 4.069
Authors: Danielle D Jandial; Salman Farshchi-Heydari; Christopher A Larson; Gregory I Elliott; Wolfgang J Wrasidlo; Stephen B Howell Journal: Clin Cancer Res Date: 2009-01-15 Impact factor: 12.531
Authors: Ansgar Brüning; Petra Burger; Marianne Vogel; Martina Rahmeh; Klaus Friese; Miriam Lenhard; Alexander Burges Journal: Invest New Drugs Date: 2008-11-28 Impact factor: 3.850