Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience
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- Fine, R.L., Gulati, A.P., Krantz, B.A. et al. Cancer Chemother Pharmacol (2013) 71: 663. doi:10.1007/s00280-012-2055-z
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We evaluated the efficacy and safety of capecitabine and temozolomide (CAPTEM) in patients with metastatic neuroendocrine tumors (NETs) to the liver. This regimen was based on our studies with carcinoid cell lines that showed synergistic cytotoxicity with sequence-specific dosing of 5-fluorouracil preceding temozolomide (TMZ).
A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LAR™ (100 %), chemotherapy (61 %), and hepatic chemoembolization (50 %). Patients received capecitabine at 600 mg/m2 orally twice daily on days 1–14 (maximum 1,000 mg orally twice daily) and TMZ 150–200 mg/m2 divided into two doses daily on days 10–14 of a 28-day cycle. Imaging was performed every 2 cycles, and serum tumor markers were measured every cycle.
Using RECIST parameters, 1 patient (5.5 %) with midgut carcinoid achieved a surgically proven complete pathological response (CR), 10 patients (55.5 %) achieved a partial response (PR), and 4 patients (22.2 %) had stable disease (SD). Total response rate was 61 %, and clinical benefit (responders and SD) was 83.2 %. Of four carcinoid cases treated with CAPTEM, there was 1 CR, 1 PR, 1 SD, and 1 progressive disease. Median progression-free survival was 14.0 months (11.3–18.0 months). Median overall survival from diagnosis of liver metastases was 83 months (28–140 months). The only grade 3 toxicity was thrombocytopenia (11 %). There were no grade 4 toxicities, hospitalizations, opportunistic infections, febrile neutropenias, or deaths.
CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.