Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2014 Aug 2:14:561.
doi: 10.1186/1471-2407-14-561.

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  1 , Paulo M Hoff
Affiliations
Clinical Trial

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

Daniel M Halperin et al. BMC Cancer. .

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.

PubMed Disclaimer

References

    1. Hazard JB, Hawk WA, Crile G., Jr Medullary (solid) carcinoma of the thyroid: A clinicopathologic entity. J Clin Endocrinol Metab. 1959;19:152–161. doi: 10.1210/jcem-19-1-152. - DOI - PubMed
    1. Brandi ML, Gagel RF, Angeli A, Bilezikian JP, Beck-Peccoz P, Bordi C, Conte-Devolx B, Falchetti A, Gheri RG, Libroia A, Lips CJ, Lombardi G, Mannelli M, Pacini F, Ponder BA, Raue F, Skogseid B, Tamburrano G, Thakker RV, Thompson NW, Tomassetti P, Tonelli F, Wells SA, Jr, Marx SJ. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab. 2001;86(12):5658–5671. doi: 10.1210/jcem.86.12.8070. - DOI - PubMed
    1. Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, Ponder MA, Telenius H, Tunnacliffe A, Ponder BAJ. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature. 1993;363(6428):458–460. doi: 10.1038/363458a0. - DOI - PubMed
    1. Boccia LM, Green JS, Joyce C, Eng C, Taylor SA, Mulligan LM. Mutation of RET codon 768 is associated with the FMTC phenotype. Clin Genet. 1997;51(2):81–85. doi: 10.1111/j.1399-0004.1997.tb02424.x. - DOI - PubMed
    1. Bolino A, Schuffenecker I, Luo Y, Seri M, Silengo M, Tocco T, Chabrier G, Houdent C, Murat A, Schlumberger M, Tourniaire J, Lenoir GM. RET mutations in exons 13 and 14 of FMTC patients. Oncogene. 1995;10(12):2415–2419. - PubMed
Pre-publication history
    1. The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2407/14/561/prepub

Publication types

MeSH terms

Associated data

LinkOut - more resources