First-line treatment of metastatic pancreatic endocrine carcinomas with capecitabine and temozolomide

Abstract

4612 Background: Pancreatic endocrine carcinomas (PECAs) are uncommon with an estimated annual incidence of 1/100,000. Approximately half are metastatic at diagnosis. Trials of cytotoxic chemotherapy have established the activity of several drugs, including streptozocin, doxorubicin, fluorouracil and dacarbazine. The oral agent temozolomide, which shares its active metabolite with dacarbazine, has also been studied in neuroendocrine tumors. The combination of capecitabine and temozolomide has been found to be synergistic for apoptosis in neuroendocrine cell lines. Early human data indicates that this combination is both effective and well tolerated. Methods: Patients with progressive metastatic PECAs received treatment with a combination of capecitabine (750mg/m2 twice daily on days 1–14) and temozolomide (200mg/m2 daily on days 10–14), on a 28 day cycle. Radiographic response rates were assessed by CT scans and evaluated according to RECIST criteria. Results: Between 9/2005 and 9/2007, 17 patients received this combination as front-line chemotherapy for metastatic PECAs. The median age was 58 (28–77) years. There were three gastrinomas (17%), two insulinomas (12%), two glucagonomas (12%), and ten nonfunctioning tumors (59%). Eight tumors were well-differentiated, two were moderately differentiated, and seven were not graded. All patients had an ECOG performance status of 0–1. Twelve patients (71%) had a partial response and five patients (29%) had stable disease. With a median follow-up of 12 months, there were no cases of disease progression. Only 1 patient (6%) experienced a grade 3/4 toxicity (idiosyncratic immune thrombocytopenia secondary to capecitabine). Conclusions: The combination of capecitabine and temozolomide appears to be a highly active and exceptionally well-tolerated front-line treatment for metastatic pancreatic endocrine carcinoma. No significant financial relationships to disclose.