A phase I study of imatinib, dacarbazine, and capecitabine in advanced endocrine cancers

Daniel M. Halperin, Alexandria T. Phan, Ana O. Hoff, Marie Aaron, James C. Yao, Paulo M. Hoff

Research output: Contribution to journalArticle

11 Scopus citations

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.Trial registration: ClinicalTrials.gov identifier NCT00354523, registered July 18, 2006.

Original languageEnglish (US)
Article number561
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - Aug 2 2014

ASJC Scopus subject areas

  • Genetics
  • Oncology
  • Cancer Research

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