Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings (Post-Meeting Edition).
Vol 24, No 18S (June 20 Supplement), 2006: 13048
© 2006 American Society of Clinical Oncology

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Abstract

Phase I/II trial of capecitabine (C), dacarbazine (D) and imatinib (I) (CDI) for patients (pts) metastatic medullary thyroid carcinomas (MTC)

M. D. Anderson Cancer Center, Houston, TX

13048

Background: MTC is a rare tumor that responds poorly to conventional chemotherapy. 5-FU and D are frequently used, with an expected response rate of around 15%. MTC is often associated with multiple endocrine neoplasia type 2, an autosomal dominant syndrome caused by a mutation in the RET proto-oncogene which encodes RET, a tyrosine kinase receptor. I is a tyrosine kinase inhibitor with activity against c-Kit, PDGF and possibly RET, and we postulated that its addition to chemotherapy would increase its efficacy against this disease. Methods: We designed a phase I/II trial combining escalating doses of oral C, IV D and oral I. Pts with any advanced solid tumors were eligible for the phase I part of the trial. Results: 13 pts were entered and 12 were eligible (7 MTC, 2 adrenocortical, 1 islet-cell, 1 insular thyroid and 1 small cell). 4 pts did not complete one cycle (1 pt withdrew after 5 days and 2 pts progressed in less than 10 days and were replaced for toxicity analysis, 1 had a DLT and is included). 3 patients were entered in dose level 1, without DLT. 2 out of 6 pts developed DLT at the second dose level (1 G 3 fatigue and 1 G3 hypokalemia). Three additional pts are being entered on dose level 1. The first one had PD after 7 days and is being replaced. For the 11 pts who were evaluable, best response was 3 SD (range 3 to 9 + months) and 8 PD. Conclusions: The combination of CDI is feasible but has resulted in an unexpected pattern of toxicity in this patient population, with fatigue and hypokalemia as the DLT. No significant diarrhea or hand-foot syndrome was seen. Only G1 and 2 fluid retention and neutropenia have been encountered. Only minor reduction in tumor size has been seen among these heavily pretreated pts. Once the phase I is complete, the trial will continue in a phase II setting for untreated MTC pts.