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.
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Acknowledgments
Support for this study was provided by the Stephen and Caroline Kaufer Fund for Neuroendocrine Tumor Research. Pemetrexed was supplied by Lilly, Inc. The authors acknowledge additional support from the Saul and Gitta Kurlat Fund for Neuroendocrine Tumor Research, and NCI grants CA093401 (MHK) and P50 CA127003 (DF/HCC SPORE in Gastrointestinal Cancer).
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Chan, J.A., Zhu, A.X., Stuart, K. et al. Phase II study of pemetrexed in patients with advanced neuroendocrine tumors. Cancer Chemother Pharmacol 66, 961–968 (2010). https://doi.org/10.1007/s00280-010-1248-6
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DOI: https://doi.org/10.1007/s00280-010-1248-6