title: A phase I study of imatinib, dacarbazine, and capecitabine in advanced endocrine cancers.
abstract: BACKGROUND
  Patients with advanced endocrine cancers, such as adrenocortical carcinoma and medullary thyroid carcinoma, have few well-validated therapeutic options. Pre-clinical studies have suggested potential activity of imatinib in these tumors. We therefore sought to establish a safe, novel treatment regimen combining imatinib with cytotoxic chemotherapy for future study in endocrine cancers.
  
  
  METHODS
  A standard 3 + 3 dose-escalation design was used with a 21-day cycle, including imatinib on days 1-21, dacarbazine on days 1-3, and capecitabine on days 1-14.
  
  
  RESULTS
  Twenty patients were treated. The most frequent toxicities were edema and fatigue, with dose-limiting fatigue and dyspnea. The recommended phase II regimen is dacarbazine 250 mg/m2 daily on day 1-3, capecitabine 500 mg/m2 twice daily on days 1-14, and imatinib 300 mg daily on days 1-21 of a 21-day cycle. Interestingly, responses were seen in patients with adrenocortical carcinoma, with 1 of 6 patients experiencing a partial response and a second experiencing a minor response, with progression-free survival of 8.8 and 6.4 months, respectively.
  
  
  CONCLUSIONS
  The regimen of imatinib, dacarbazine, and capecitabine is well-tolerated. It may have some activity in adrenocortical carcinoma, and further study of this combination or its components may be beneficial for this disease with limited treatment options.
  
  
  BACKGROUND
  ClinicalTrials.gov identifier NCT00354523, registered July 18, 2006.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Halperin
authors.forename: Alexandria T
authors.initials: AT
authors.lastname: Phan
authors.forename: Ana O
authors.initials: AO
authors.lastname: Hoff
authors.forename: Marie
authors.initials: M
authors.lastname: Aaron
authors.affiliation: Department of Gastrointestinal Medical Oncology, The University of Texas M, D, Anderson Cancer Center, Houston, Texas, USA. jyao@mdanderson.org.
authors.forename: James C
authors.initials: JC
authors.lastname: Yao
authors.forename: Paulo M
authors.initials: PM
authors.lastname: Hoff
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D001549:Benzamides / Q000008:administration & dosage / Q000627:therapeutic use; D000069287:Capecitabine; D003606:Dacarbazine / Q000008:administration & dosage / Q000627:therapeutic use; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004701:Endocrine Gland Neoplasms / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D000068877:Imatinib Mesylate; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage / Q000627:therapeutic use; D011743:Pyrimidines / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D003841:Deoxycytidine; D000069287:Capecitabine; D003606:Dacarbazine; D000068877:Imatinib Mesylate; D005472:Fluorouracil
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