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.

TRIAL REGISTRATION:

ClinicalTrials.gov identifier NCT00354523, registered July 18, 2006.

• Authors: Daniel M Halperin, Alexandria T Phan, Ana O Hoff, Marie Aaron, James C Yao, Paulo M Hoff
• Journal: BMC cancer (BMC Cancer) Vol. 14 Pg. 561 (Aug 02 2014) ISSN: 1471-2407 [Electronic] England
• PMID: 25086465 (Publication Type: Clinical Trial, Phase I, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Benzamides
• Piperazines
• Pyrimidines
• Deoxycytidine
• Capecitabine
• Dacarbazine
• Imatinib Mesylate
• Fluorouracil

Topics

• Adult
• Aged
• Antineoplastic Agents (administration & dosage, therapeutic use)
• Antineoplastic Combined Chemotherapy Protocols (administration & dosage, adverse effects)
• Benzamides (administration & dosage, therapeutic use)
• Capecitabine
• Dacarbazine (administration & dosage, therapeutic use)
• Deoxycytidine (administration & dosage, analogs & derivatives, therapeutic use)
• Disease-Free Survival
• Drug Administration Schedule
• Endocrine Gland Neoplasms (drug therapy, pathology)
• Female
• Fluorouracil (administration & dosage, analogs & derivatives, therapeutic use)
• Humans
• Imatinib Mesylate
• Male
• Middle Aged
• Piperazines (administration & dosage, therapeutic use)
• Pyrimidines (administration & dosage, therapeutic use)
• Treatment Outcome