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

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

SUBMITTER: Halperin DM

PROVIDER: S-EPMC4125701 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature

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

Halperin Daniel M DM Phan Alexandria T AT Hoff Ana O AO Aaron Marie M Yao James C JC Hoff Paulo M PM

BMC cancer 20140802

<h4>Background</h4>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.<h4>Methods</h4>A standard 3 + 3 dose-escalation design was used with a 21-day cycle, includin ...[more]

PMID: 25086465

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Project description:PurposeTo examine the response rate of gross chemo-refractory breast cancer treated with concurrent capecitabine (CAP) and radiation therapy in a prospective Phase II study.Methods and materialsBreast cancer patients with inoperable disease after chemotherapy, residual nodal disease after definitive surgical resection, unresectable chest wall or nodal recurrence after a prior mastectomy, or oligometastatic disease were eligible. Response by RECIST criteria was assessed after 45 Gy. Conversion to operable, locoregional control, and grade ≥3 toxicities were assessed. The first 9 patients received CAP 825 mg/m2 twice daily continuously. Because of toxicity, subsequent patients received CAP only on radiation days. Kaplan-Meier analysis was used to estimate overall survival (OS) and locoregional recurrence-free survival.ResultsFrom 2009 to 2012, 32 patients were accrued; 26 received protocol-specified treatment. Median follow-up was 12.9 months (interquartile range, 7.10-42.9 months). Nineteen patients (73%) had partial or complete response. Fourteen patients (53.9%) experienced grade 3 non-dermatitis toxicity (7 of 9 continuous dosing). Three of four inoperable patients converted to operable. One-year actuarial OS in the treated cohort was 54%. The trial was stopped early after interim analysis suggested futility independent of response. Treatment was deemed futile (ie, conversion to operable but M1 disease immediately postoperatively) in 9 of 10 patients with triple-negative (TN) versus 6 of 16 with non-TN disease (P=.014). Median OS and 1-year locoregional recurrence-free survival among non-TN versus TN patients was 22.8 versus 5.1 months, and 63% versus 20% (P=.007).ConclusionsCapecitabine can be safely administered on radiation days with careful clinical monitoring and was associated with encouraging response in this chemo-refractory cohort. However, patients with TN breast cancer had poor outcomes even when response was achieved. Further study in non-TN patients may be warranted.

Dataset Information

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

Publications

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

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