BACKGROUND: The objectives of this study were to provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain it and to collect broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. (ClinicalTrials.gov identifier NCT00094029). METHODS: Imatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule of 50 mg daily in 6-week cycles (4 weeks on treatment, 2 weeks off treatment). Tumor assessment frequency was according to local practice, and response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post hoc analyses evaluated different patterns of treatment management. RESULTS: At final data cutoff, 1124 patients comprised the intent-to-treat population, and 15% of these patients had a baseline Eastern Cooperative Oncology Group performance status ≥2. The median treatment duration was 7.0 months. The median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0-9.4 months), the median OS was 16.6 months (95% CI, 14.9-18.0 months), and 36% of patients were alive at the time of analysis. Patients for whom the initial dosing schedule was modified exhibited longer median OS (23.5 months) than those who were treated strictly according to the initial dosing schedule (11.1 months). The most common treatment-related grade 3 and 4 adverse events were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related adverse events associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of ≤1% each. CONCLUSIONS: This treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure.
BACKGROUND: The objectives of this study were to provide sunitinib to patients with gastrointestinal stromal tumor (GIST) who were otherwise unable to obtain it and to collect broad safety and efficacy data from a large population of patients with advanced GIST after imatinib failure. (ClinicalTrials.gov identifier NCT00094029). METHODS:Imatinib-resistant/intolerant patients with advanced GIST received sunitinib on an initial dosing schedule of 50 mg daily in 6-week cycles (4 weeks on treatment, 2 weeks off treatment). Tumor assessment frequency was according to local practice, and response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors version 1.0. Overall survival (OS) and safety were assessed regularly. Post hoc analyses evaluated different patterns of treatment management. RESULTS: At final data cutoff, 1124 patients comprised the intent-to-treat population, and 15% of these patients had a baseline Eastern Cooperative Oncology Group performance status ≥2. The median treatment duration was 7.0 months. The median time to tumor progression was 8.3 months (95% confidence interval [CI], 8.0-9.4 months), the median OS was 16.6 months (95% CI, 14.9-18.0 months), and 36% of patients were alive at the time of analysis. Patients for whom the initial dosing schedule was modified exhibited longer median OS (23.5 months) than those who were treated strictly according to the initial dosing schedule (11.1 months). The most common treatment-related grade 3 and 4 adverse events were hand-foot syndrome (11%), fatigue (9%), neutropenia (8%), hypertension (7%), and thrombocytopenia (6%). Treatment-related adverse events associated with cardiac function (eg, congestive heart failure and myocardial infarction) were reported at frequencies of ≤1% each. CONCLUSIONS: This treatment-use study confirms the long-term safety and efficacy of sunitinib in a large international population of patients with advanced GIST after imatinib failure.
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: George D Demetri; Allan T van Oosterom; Christopher R Garrett; Martin E Blackstein; Manisha H Shah; Jaap Verweij; Grant McArthur; Ian R Judson; Michael C Heinrich; Jeffrey A Morgan; Jayesh Desai; Christopher D Fletcher; Suzanne George; Carlo L Bello; Xin Huang; Charles M Baum; Paolo G Casali Journal: Lancet Date: 2006-10-14 Impact factor: 79.321
Authors: S Hirota; K Isozaki; Y Moriyama; K Hashimoto; T Nishida; S Ishiguro; K Kawano; M Hanada; A Kurata; M Takeda; G Muhammad Tunio; Y Matsuzawa; Y Kanakura; Y Shinomura; Y Kitamura Journal: Science Date: 1998-01-23 Impact factor: 47.728
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: S George; J Y Blay; P G Casali; A Le Cesne; P Stephenson; S E Deprimo; C S Harmon; C N J Law; J A Morgan; I Ray-Coquard; V Tassell; D P Cohen; G D Demetri Journal: Eur J Cancer Date: 2009-03-11 Impact factor: 9.162
Authors: George D Demetri; Michael C Heinrich; Jonathan A Fletcher; Christopher D M Fletcher; Annick D Van den Abbeele; Christopher L Corless; Cristina R Antonescu; Suzanne George; Jeffrey A Morgan; Ming Hui Chen; Carlo L Bello; Xin Huang; Darrel P Cohen; Charles M Baum; Robert G Maki Journal: Clin Cancer Res Date: 2009-09-08 Impact factor: 12.531
Authors: Michael C Heinrich; Christopher L Corless; Anette Duensing; Laura McGreevey; Chang-Jie Chen; Nora Joseph; Samuel Singer; Diana J Griffith; Andrea Haley; Ajia Town; George D Demetri; Christopher D M Fletcher; Jonathan A Fletcher Journal: Science Date: 2003-01-09 Impact factor: 47.728
Authors: David Tamoschus; Katja Draexler; Jane Chang; Christopher Ngai; Matthew Madin-Warburton; Ashley Pitcher Journal: Clin Drug Investig Date: 2017-06 Impact factor: 2.859
Authors: Brent A Willobee; Hallie J Quiroz; Matthew S Sussman; Chad M Thorson; Juan E Sola; Eduardo A Perez Journal: Transl Gastroenterol Hepatol Date: 2018-08-08
Authors: Shruti Choudhary; Arpit Doshi; Lerin Luckett-Chastain; Michael Ihnat; Ernest Hamel; Susan L Mooberry; Aleem Gangjee Journal: Bioorg Med Chem Date: 2021-02-12 Impact factor: 3.641