A phase I study of imatinib, dacarbazine, and capecitabine in advanced endocrine cancers. BMC Cancer 2014 Aug 02;14:561
Date
08/05/2014Pubmed ID
25086465Pubmed Central ID
PMC4125701DOI
10.1186/1471-2407-14-561Scopus ID
2-s2.0-84924804904 (requires institutional sign-in at Scopus site) 12 CitationsAbstract
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.
Author List
Halperin DM, Phan AT, Hoff AO, Aaron M, Yao JC, Hoff PMAuthor
Alexandria T. Phan MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Antineoplastic Agents
Antineoplastic Combined Chemotherapy Protocols
Benzamides
Capecitabine
Dacarbazine
Deoxycytidine
Disease-Free Survival
Drug Administration Schedule
Endocrine Gland Neoplasms
Female
Fluorouracil
Humans
Imatinib Mesylate
Male
Middle Aged
Piperazines
Pyrimidines
Treatment Outcome
