title: Clinical outcomes of patients with gastrointestinal stromal tumor in phase I clinical trials.
abstract: The prognosis of patients with gastrointestinal stromal tumor (GIST) after the failure of standard therapies is poor with supportive care alone. Guidelines recommend clinical trials, and patients with good performance status following standard therapies are often eligible for phase I clinical trials of investigational agents; however, there are no detailed reports on the clinical outcomes of GIST patients enrolled in these trials.
  
  
  
  We retrospectively reviewed the clinical outcomes of 21 consecutive GIST patients who were enrolled in one or more phase I clinical trials at a single center between March 2009 and November 2014.
  
  
  
  The median age was 57 years, and the median number of previous lines of standard chemotherapy was three. Chemotherapy before enrollment in a phase I clinical trial included imatinib, sunitinib, and regorafenib in 100, 95, and 43 % of patients, respectively. None of the patients achieved objective response. Ten patients (47.6 %) were determined to be stable according to the Response Evaluation Criteria in Solid Tumors; four of them (19.0 %) maintained their status for more than 24 weeks. Four patients achieved partial response according to the Choi criteria. No dose-limiting toxicity was observed; however, severe adverse events and grade 3 or higher toxicities were reported in one (4.8 %) and two patients (9.5 %), respectively. Although no treatment-related deaths occurred, one patient (4.8 %) died within 30 days after the last drug administration because of disease progression. The median progression-free survival was 1.9 months, and the median overall survival time has not been reached.
  
  
  
  Data suggested that phase I clinical trials were feasible and may provide prognostic benefits to GIST patients after standard therapies, indicating that enrollment in these studies may provide a treatment option for these patients.
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nagatani
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan. kshitara@east.ncc.go.jp.
authors.forename: Kohei
authors.initials: K
authors.lastname: Shitara
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Hideaki
authors.initials: H
authors.lastname: Bando
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kuboki
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Wataru
authors.initials: W
authors.lastname: Okamoto
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Yoshino
authors.affiliation: Department of Surgery, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Toshirou
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Atushi
authors.initials: A
authors.lastname: Ohtsu
authors.affiliation: Department of Gastroenterology and Gastrointestinal Oncology, National Cancer Center Hospital East (NCCHE), 6-5-1 Kashiwanoha, Kashiwa, Chiba, 277-8577, Japan.
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Doi
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use; D017321:Clinical Trials, Phase I as Topic; D003131:Combined Modality Therapy; D005260:Female; D046152:Gastrointestinal Stromal Tumors / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D019233:Retreatment; D012189:Retrospective Studies; D017211:Treatment Failure; D016896:Treatment Outcome
keywords: Gastrointestinal stromal tumor; Investigational agent; Phase I clinical trial; Systemic chemotherapy