Metronomic capecitabine in advanced well or moderately differentiated neuroendocrine carcinomas.

Abstract

e13130 Background: Conventional chemotherapy is not a standard of care for well or moderately differentiated neuroendocrine carcinomas (NECs). 5-fluorouracil (5FU) as a protracted venous infusion (PVI) showed some activity in this setting. Metronomic capecitabine (MC) is the oral alternative to PVI 5FU, avoiding a central venous device and elastomeric pump. We report our experience with MC in patients with advanced NECs. Methods: We retrospectively reviewed the clinical records of 23 patients with metastatic well or moderately differentiated NECs treated with MC at the European Institute of Oncology from Milan, between July 2005 and August 2009. Results: M/F ratio was 13/10, median age 56 years (range: 30-77). Seventeen patients (73%) had well- differentiated NECs, 1 had typical and 5 atypical PCs. Primary sites of tumor were pancreas/ileum/thyroid/lung/unknown in 48%, 9%, 4%, 26%, and 13% of patients, respectively. The Ki-67 was < 2% in 2 patients (9%), 3-19% in 16 (70%), and not performed in the other cases (22%). Twenty-two patients (96%) were pretreated. Baseline status of tumor was progression of disease (PD) in 16 (69%) patients, and stable disease (SD) in 7 (31%). MC was orally administered at 1,000-2,000 mg daily, continuously. Median duration of therapy was 7 months (range 3 days-31 months). In 11 patients (48%) a SD was observed, in 7 (30%) PD, and 5 (22%) were not evaluable. Median time to progression was 19 months (range: 2-31). Study treatment was discontinued due to PD in 9 patients (39%), and toxicity in 2 patients (9%). Twelve patients (52%) are currently on study treatment. Toxicity included 1 very early coronary spasm in a patient with a negative cardiac history, one grade 3 neutropenia, one grade 2 skin toxicity. After a 24 months median follow-up (range: 2-31) 5 patients (22%) died. Conclusions: Metronomic capecitabine is well tolerated and moderately active in patients with advanced well/moderately differentiated NECs. Cardiac toxicity seems to be independent from the drug dose and underlying cardiac status of the patient. Combination studies with biologic agents or other metronomic therapies are warranted. No significant financial relationships to disclose.