Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center a
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ORIGINAL ARTICLE
Capecitabine and temozolomide (CAPTEM) for metastatic, well-differentiated neuroendocrine cancers: The Pancreas Center at Columbia University experience Robert L. Fine • Anthony P. Gulati • Benjamin A. Krantz • Rebecca A. Moss • Stephen Schreibman • Dawn A. Tsushima • Kelley B. Mowatt • Richard D. Dinnen • Yuehua Mao • Peter D. Stevens • Beth Schrope John Allendorf • James A. Lee • William H. Sherman • John A. Chabot
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Received: 6 November 2012 / Accepted: 10 December 2012 / Published online: 31 January 2013 Ó Springer-Verlag Berlin Heidelberg 2013
Abstract Purpose 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). Methods A retrospective review was conducted of 18 patients with NETs metastatic to the liver who had failed 60 mg/month of Sandostatin LARTM (100 %), chemotherapy (61 %), and hepatic chemoembolization (50 %). Patients received capecitabine at 600 mg/m2 orally twice
R. L. Fine (&) A. P. Gulati B. A. Krantz D. A. Tsushima K. B. Mowatt R. D. Dinnen Y. Mao W. H. Sherman Division of Medical Oncology, Experimental Therapeutics Program, The Pancreas Center at Columbia, New York Presbyterian-Columbia University Medical Center, William Black Research Building, Room 20-05, 650 West 168th Street, New York, NY 10032, USA e-mail: [email protected]
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. Results 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. Conclusions CAPTEM is highly active, well tolerated and may prolong survival in patients with well-differentiated, metastatic NET who have progressed on previous therapies.
R. A. Moss Division of Medical Oncology, Cancer Institute of New Jersey, Robert Wood Johnson Medical School, UMDNJ, New Brunswick, NJ, USA
Keywords Neuroendocrine cancer Capecitabine Temozolomide Carcinoid
S. Schreibman Hematology-Oncology Associates, Carol Simon Cancer Center, Morristown Memorial Hospital, Morristown, NJ, U
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