Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 5, pp 961–968

Phase II study of pemetrexed in patients with advanced neuroendocrine tumors

  • Jennifer A. Chan
  • Andrew X. Zhu
  • Keith Stuart
  • Pankaj Bhargava
  • Craig C. Earle
  • Jeffrey W. Clark
  • Carolyn Casey
  • Eileen Regan
  • Matthew H. Kulke
Original Article

DOI: 10.1007/s00280-010-1248-6

Cite this article as:
Chan, J.A., Zhu, A.X., Stuart, K. et al. Cancer Chemother Pharmacol (2010) 66: 961. doi:10.1007/s00280-010-1248-6

Abstract

Purpose

In some reports, 5-fluorouracil has been associated with modest activity in patients with neuroendocrine tumors. Pemetrexed is a multitargeted antifolate with activity in tumor types not significantly responsive to other antifolates. We evaluated the efficacy of pemetrexed in a phase II study of patients with advanced neuroendocrine tumors.

Methods

Patients with metastatic neuroendocrine tumors (excluding small-cell carcinoma) were treated with pemetrexed administered intravenously at a dose of 500 mg/m2 every 21 days. To reduce potential toxicity, patients also received folic acid, vitamin B12 supplementation, and peri-infusional treatment with dexamethasone. Patients were followed for response, toxicity, and survival.

Results

The study was designed with a total accrual goal of 32 patients. Due to lack of radiographic responses in patients during the study period, accrual was terminated at 17. However, one patient achieved a delayed partial response following discontinuation of pemetrexed. Ten patients were evaluable for biochemical response; five (50%) experienced >50% decrease in plasma chromogranin A. Among the 17 patients, 5 (29%) discontinued therapy due to treatment-related toxicity. The median overall survival was 12.1 months.

Conclusion

Pemetrexed does not appear to have significant antitumor activity in patients with advanced neuroendocrine tumors. The limited antitumor activity and potential toxicity associated with pemetrexed mirrors experience with the majority of other cytotoxic agents in patients with neuroendocrine tumors. Investigation of novel, molecularly targeted agents may offer more promise in this disease.

Keywords

Pemetrexed Neuroendocrine tumor Carcinoid tumor Pancreatic neuroendocrine tumor 

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Jennifer A. Chan
    • 1
  • Andrew X. Zhu
    • 2
  • Keith Stuart
    • 3
  • Pankaj Bhargava
    • 1
  • Craig C. Earle
    • 1
  • Jeffrey W. Clark
    • 2
  • Carolyn Casey
    • 1
  • Eileen Regan
    • 1
  • Matthew H. Kulke
    • 1
  1. 1.Department of Medical OncologyDana-Farber Cancer InstituteBostonUSA
  2. 2.Division of Hematology/OncologyMassachusetts General HospitalBostonUSA
  3. 3.Division of Hematology/OncologyBeth Israel Deaconess Medical CenterBostonUSA

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