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Published on: July 31, 2016
Phase II study of pemetrexed in patients with advanced neuroendocrine tumors
Jennifer A Chan1, Andrew X Zhu, Keith Stuart
1Department of Medical Oncology, Dana-Farber Cancer Institute, Dana 1220, Boston, MA, 02115, USA. jang@partners.org
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/m(2) 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.
Insights
Pemetrexed showed limited antitumor activity in advanced neuroendocrine tumors. Further research into novel targeted agents is recommended for better treatment outcomes in this patient population.
Area of Science:
- Medical Oncology
- Pharmacology
Background:
- Neuroendocrine tumors (NETs) are a heterogeneous group of malignancies.
- 5-fluorouracil has shown modest activity in some NET patients.
- Pemetrexed is a multitargeted antifolate with efficacy in various cancers.
Purpose of the Study:
- To evaluate the efficacy of pemetrexed in patients with advanced neuroendocrine tumors.
- To assess response rates, toxicity, and survival in this patient cohort.
Main Methods:
- A phase II study was conducted involving patients with metastatic neuroendocrine tumors (excluding small-cell carcinoma).
- Pemetrexed was administered intravenously at 500 mg/m(2) every 21 days.
- Patients received folic acid, vitamin B12, and dexamethasone to mitigate toxicity.
Main Results:
- Accrual was terminated early at 17 patients due to a lack of radiographic responses.
- One patient achieved a partial response after discontinuing pemetrexed.
- 50% of evaluable patients had a >50% decrease in plasma chromogranin A; median overall survival was 12.1 months.
- 29% of patients discontinued therapy due to toxicity.
Conclusions:
- Pemetrexed demonstrates limited antitumor activity in advanced neuroendocrine tumors.
- The observed activity and toxicity profile of pemetrexed are consistent with other cytotoxic agents used for NETs.
- Future investigations should focus on novel, molecularly targeted agents for improved therapeutic outcomes in NETs.
