Original Article

Cancer Chemotherapy and Pharmacology

, Volume 66, Issue 5, pp 961-968

First online:

Phase II study of pemetrexed in patients with advanced neuroendocrine tumors

  • Jennifer A. ChanAffiliated withDepartment of Medical Oncology, Dana-Farber Cancer Institute Email author 
  • , Andrew X. ZhuAffiliated withDivision of Hematology/Oncology, Massachusetts General Hospital
  • , Keith StuartAffiliated withDivision of Hematology/Oncology, Beth Israel Deaconess Medical Center
  • , Pankaj BhargavaAffiliated withDepartment of Medical Oncology, Dana-Farber Cancer Institute
  • , Craig C. EarleAffiliated withDepartment of Medical Oncology, Dana-Farber Cancer Institute
  • , Jeffrey W. ClarkAffiliated withDivision of Hematology/Oncology, Massachusetts General Hospital
  • , Carolyn CaseyAffiliated withDepartment of Medical Oncology, Dana-Farber Cancer Institute
  • , Eileen ReganAffiliated withDepartment of Medical Oncology, Dana-Farber Cancer Institute
  • , Matthew H. KulkeAffiliated withDepartment of Medical Oncology, Dana-Farber Cancer Institute

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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