title: Sunitinib in patients with imatinib-resistant gastrointestinal stromal tumor: A single center experience study.
abstract: OBJECTIVE
  The outcome of patients with advanced gastrointestinal stromal tumor (GIST) has improved with the use of imatinib. Despite high response rates with this drug resistance eventually develops in nearly all patients. We present an analysis of prospectively collected data on sunitinib efficacy and safety in patients with imatinib-resistant GIST.
  
  
  METHODS
  Between November 2006 and October 2007, patients with GIST were accrued in an approved sunitinib patient access protocol. Key eligibility criteria included tumor resistance to imatinib and/or patient intolerance to this drug. Patients received sunitinib at a starting dose of 50 mg once daily for 4 weeks in a 6 week cycle, with standardized dose modification titrated to toxicity. Patients were continued on sunitinib until disease progression or unacceptable toxicity. The endpoints were safety, overall survival (OS) and objective response rate (ORR).
  
  
  RESULTS
  Fifteen patients, all of whom had imatinib resistance and none intolerance, with median age of 48 (26-69) years, were treated on the protocol. The most common sites of primary disease were small intestine (40%), stomach (26.7%) and retroperitoneal (26.7%). A median of 10 (1-47) cycles of sunitinib were delivered, 9 (60%) patients required dose reductions due to toxicity whereas dose delay of > 2 weeks was required in only one (6.7%) patient. There were no toxicity-related drug discontinuations. Hypothyroidism (n = 4; 26.7%) and hand-foot syndrome (n = 3; 20%) were the most common toxicities. There were no complete and 4 (26.7%) partial responses while prolonged disease stability was seen in 8 (53.3%) patients. At a median follow-up of 81 months in surviving patients, the median progression-free and overall survivals were 15.5 and 18.7 months, respectively.
  
  
  CONCLUSIONS
  Sunitinib appears to be an effective and well-tolerated treatment for Indian patients with imatinib-resistant GIST with outcomes similar to that reported previously. Adverse effects can be reasonably well managed using a dose modification strategy.
authors.forename: A
authors.initials: A
authors.lastname: Sahu
authors.forename: S
authors.initials: S
authors.lastname: Godbole
authors.forename: P
authors.initials: P
authors.lastname: Jain
authors.forename: J
authors.initials: J
authors.lastname: Ghosh
authors.forename: S
authors.initials: S
authors.lastname: Shrikhande
authors.forename: M
authors.initials: M
authors.lastname: Ramadwar
authors.forename: M
authors.initials: M
authors.lastname: Goyal
authors.forename: S
authors.initials: S
authors.lastname: Gulia
authors.forename: J
authors.initials: J
authors.lastname: Bajpai
authors.forename: Y
authors.initials: Y
authors.lastname: Kembhavi
authors.affiliation: Department of Medical Oncology, Tata Memorial Centre, Mumbai, Maharashtra, India.
authors.forename: S
authors.initials: S
authors.lastname: Gupta
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007211:Indoles / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000627:therapeutic use*; D000077210:Sunitinib; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D007211:Indoles; D011758:Pyrroles; D000077210:Sunitinib