PURPOSE: To evaluate the maximum tolerated dose (MTD), safety, and antitumor activity of sunitinib combined with paclitaxel and carboplatin. METHODS: Successive cohorts of patients with advanced solid tumors received oral sunitinib (25, 37.5, or 50 mg) for 2 consecutive weeks of a 3-week cycle (Schedule 2/1) or as a continuous daily dose for 3-week cycles (CDD schedule) in combination with paclitaxel (175-200 mg/m(2)) plus carboplatin (AUC 6 mg min/ml) on day one of each of 4 cycles. Dose-limiting toxicities (DLTs) and adverse events (AEs) were evaluated to determine the MTD. Efficacy parameters were analyzed in patients with measurable disease. RESULTS: Forty-three patients were enrolled (n = 25 Schedule 2/1; n = 18 CDD schedule). Across all doses, 6 DLTs were observed [grade 4 papilledema, grade 5 GI hemorrhage, grade 3 neutropenic infection, and grade 4 thrombocytopenia (n = 3)]. The MTD for Schedule 2/1 was sunitinib 25 mg plus paclitaxel 175 mg/m(2) and carboplatin AUC 6 mg min/ml. The MTD was not determined for the CDD schedule. Treatment-related AEs included neutropenia (77%), thrombocytopenia (56%), and fatigue (47%). Of 38 evaluable patients, 4 (11%) had partial responses and 12 (32%) had stable disease. PK data indicated an increase in maximum and total plasma exposures to sunitinib and its active metabolite when given with paclitaxel and carboplatin compared with sunitinib monotherapy. CONCLUSIONS: Myelosuppression resulting in prolonged dose delays and frequent interruptions was observed, suggesting that this treatment combination is not feasible in the general cancer population.
PURPOSE: To evaluate the maximum tolerated dose (MTD), safety, and antitumor activity of sunitinib combined with paclitaxel and carboplatin. METHODS: Successive cohorts of patients with advanced solid tumors received oral sunitinib (25, 37.5, or 50 mg) for 2 consecutive weeks of a 3-week cycle (Schedule 2/1) or as a continuous daily dose for 3-week cycles (CDD schedule) in combination with paclitaxel (175-200 mg/m(2)) plus carboplatin (AUC 6 mg min/ml) on day one of each of 4 cycles. Dose-limiting toxicities (DLTs) and adverse events (AEs) were evaluated to determine the MTD. Efficacy parameters were analyzed in patients with measurable disease. RESULTS: Forty-three patients were enrolled (n = 25 Schedule 2/1; n = 18 CDD schedule). Across all doses, 6 DLTs were observed [grade 4 papilledema, grade 5 GI hemorrhage, grade 3 neutropenic infection, and grade 4 thrombocytopenia (n = 3)]. The MTD for Schedule 2/1 was sunitinib 25 mg plus paclitaxel 175 mg/m(2) and carboplatin AUC 6 mg min/ml. The MTD was not determined for the CDD schedule. Treatment-related AEs included neutropenia (77%), thrombocytopenia (56%), and fatigue (47%). Of 38 evaluable patients, 4 (11%) had partial responses and 12 (32%) had stable disease. PK data indicated an increase in maximum and total plasma exposures to sunitinib and its active metabolite when given with paclitaxel and carboplatin compared with sunitinib monotherapy. CONCLUSIONS:Myelosuppression resulting in prolonged dose delays and frequent interruptions was observed, suggesting that this treatment combination is not feasible in the general cancer population.
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Authors: P Therasse; S G Arbuck; E A Eisenhauer; J Wanders; R S Kaplan; L Rubinstein; J Verweij; M Van Glabbeke; A T van Oosterom; M C Christian; S G Gwyther Journal: J Natl Cancer Inst Date: 2000-02-02 Impact factor: 13.506
Authors: Dirk B Mendel; A Douglas Laird; Xiaohua Xin; Sharianne G Louie; James G Christensen; Guangmin Li; Randall E Schreck; Tinya J Abrams; Theresa J Ngai; Leslie B Lee; Lesley J Murray; Jeremy Carver; Emily Chan; Katherine G Moss; Joshua O Haznedar; Juthamas Sukbuntherng; Robert A Blake; Li Sun; Cho Tang; Todd Miller; Sheri Shirazian; Gerald McMahon; Julie M Cherrington Journal: Clin Cancer Res Date: 2003-01 Impact factor: 12.531
Authors: G Fountzilas; H P Kalofonos; U Dafni; C Papadimitriou; D Bafaloukos; P Papakostas; A Kalogera-Fountzila; H Gogas; G Aravantinos; L A Moulopoulos; T Economopoulos; D Pectasides; N Maniadakis; V Siafaka; E Briasoulis; C Christodoulou; D Tsavdaridis; P Makrantonakis; E Razis; P Kosmidis; D Skarlos; M A Dimopoulos Journal: Ann Oncol Date: 2004-10 Impact factor: 32.976
Authors: Véronique Diéras; Thomas Bachelot; Mario Campone; Nicolas Isambert; Florence Joly; Christophe Le Tourneau; Philippe Cassier; Emmanuelle Bompas; Pierre Fumoleau; Sabine Noal; Christine Orsini; Marta Jimenez; Diane Charlotte Imbs; Etienne Chatelut Journal: Oncol Ther Date: 2016-08-18