Peter G Rose1, Mary Smrekar, Pam Haba, Nancy Fusco, Michael Rodriguez. 1. Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Cleveland Clinic Foundation/Case Western Reserve University, Cleveland, OH 44195, USA. rosep@ccf.org
Abstract
OBJECTIVES: The feasibility, safety, and preliminary efficacy of a second-line combination therapy for oral topotecan and pegylated liposomal doxorubicin in patients with platinum-resistant or refractory epithelial ovarian, peritoneal, or tubal carcinoma were investigated in this phase I trial. METHODS: A fixed dose of oral topotecan 2.3 or 1.53 mg/m(2) on days 1 through 5 and escalating doses of pegylated liposomal doxorubicin on day 1 of a 28-day cycle were administered. Dose-limiting toxicities and maximum tolerated doses were recorded. Safety was assessed by adverse event monitoring, and complete and partial responses were recorded. RESULTS: Twenty-two patients received a total of 61 courses of therapy. The maximum tolerated dose of combination therapy was 1.53 mg/m(2) of topotecan on days 1 through 5 and 40 mg/m(2) of pegylated liposomal doxorubicin on day 1 of a 28-day cycle. Because of cumulative thrombocytopenia, the dose of topotecan was decreased by one-third from 2.3 to 1.53 mg/m(2) in an effort to increase the dose of pegylated liposomal doxorubicin. Only 5 patients completed >4 cycles of therapy. The most common grade 4 adverse events at dose level 4 were neutropenia (5/9 patients) and leukopenia (2/9 patients). Overall responses were observed in 2 of 22 patients. CONCLUSIONS: Oral topotecan and pegylated liposomal doxorubicin can be combined at doses that are active as monotherapies. However, the overall response rates after monotherapy in patients with platinum-resistant ovarian cancer are comparable to or higher than those observed in this phase I study of combination therapy.
OBJECTIVES: The feasibility, safety, and preliminary efficacy of a second-line combination therapy for oral topotecan and pegylated liposomal doxorubicin in patients with platinum-resistant or refractory epithelial ovarian, peritoneal, or tubal carcinoma were investigated in this phase I trial. METHODS: A fixed dose of oral topotecan 2.3 or 1.53 mg/m(2) on days 1 through 5 and escalating doses of pegylated liposomal doxorubicin on day 1 of a 28-day cycle were administered. Dose-limiting toxicities and maximum tolerated doses were recorded. Safety was assessed by adverse event monitoring, and complete and partial responses were recorded. RESULTS: Twenty-two patients received a total of 61 courses of therapy. The maximum tolerated dose of combination therapy was 1.53 mg/m(2) of topotecan on days 1 through 5 and 40 mg/m(2) of pegylated liposomal doxorubicin on day 1 of a 28-day cycle. Because of cumulative thrombocytopenia, the dose of topotecan was decreased by one-third from 2.3 to 1.53 mg/m(2) in an effort to increase the dose of pegylated liposomal doxorubicin. Only 5 patients completed >4 cycles of therapy. The most common grade 4 adverse events at dose level 4 were neutropenia (5/9 patients) and leukopenia (2/9 patients). Overall responses were observed in 2 of 22 patients. CONCLUSIONS: Oral topotecan and pegylated liposomal doxorubicin can be combined at doses that are active as monotherapies. However, the overall response rates after monotherapy in patients with platinum-resistant ovarian cancer are comparable to or higher than those observed in this phase I study of combination therapy.
Authors: Lot A Devriese; Petronella Els O Witteveen; Marja Mergui-Roelvink; Deborah A Smith; Lionel D Lewis; David S Mendelson; Yung-Jue Bang; Hyun Choel Chung; Mohammed M Dar; Alwin D R Huitema; Jos H Beijnen; Emile E Voest; Jan H M Schellens Journal: Br J Clin Pharmacol Date: 2015-05-20 Impact factor: 4.335
Authors: S McMeekin; R Patel; C Verschraegen; P Celano; J Burke; S Plaxe; P Ghatage; M Giurescu; C Stredder; Y Wang; T Schmelter Journal: Br J Cancer Date: 2011-11-22 Impact factor: 7.640