Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 3, pp 663–670

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
Original Article

DOI: 10.1007/s00280-012-2055-z

Cite this article as:
Fine, R.L., Gulati, A.P., Krantz, B.A. et al. Cancer Chemother Pharmacol (2013) 71: 663. doi:10.1007/s00280-012-2055-z

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 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.

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.

Keywords

Neuroendocrine cancer Capecitabine Temozolomide Carcinoid 

Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Robert L. Fine
    • 1
  • Anthony P. Gulati
    • 1
  • Benjamin A. Krantz
    • 1
  • Rebecca A. Moss
    • 2
  • Stephen Schreibman
    • 3
  • Dawn A. Tsushima
    • 1
  • Kelley B. Mowatt
    • 1
  • Richard D. Dinnen
    • 1
  • Yuehua Mao
    • 1
  • Peter D. Stevens
    • 4
  • Beth Schrope
    • 5
  • John Allendorf
    • 5
  • James A. Lee
    • 5
  • William H. Sherman
    • 1
  • John A. Chabot
    • 5
  1. 1.Division of Medical Oncology, Experimental Therapeutics Program, The Pancreas Center at ColumbiaNew York Presbyterian-Columbia University Medical CenterNew YorkUSA
  2. 2.Division of Medical Oncology, Cancer Institute of New JerseyRobert Wood Johnson Medical School, UMDNJNew BrunswickUSA
  3. 3.Hematology-Oncology Associates, Carol Simon Cancer CenterMorristown Memorial HospitalMorristownUSA
  4. 4.Division of Gastroenterology, Endoscopic and Interventional ServiceThe Pancreas Center at ColumbiaNew YorkUSA
  5. 5.Division of Gastrointestinal and Endocrine SurgeryThe Pancreas Center at ColumbiaNew YorkUSA

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