Pemetrexed in head and neck cancer: a systematic review

Pemetrexed has been evaluated as a novel chemotherapeutic for head and neck cancer (HNC). In this review, we examined the efficacy and tolerability of pemetrexed in patients with HNC. Relevant English-language literature was identified via PubMed and a review of published abstracts from the American Society of Clinical Oncology and European Society for Medical Oncology annual meetings from January 2000 through September 2012. Search terms were "pemetrexed" (or "LY231514") and "head and neck cancer." Completed prospective phase I to III trials of pemetrexed alone or in combination with other agents or radiotherapy evaluating objective response rate (ORR), progression-free survival (PFS), and/or overall survival (OS) were eligible; ten studies were reviewed. Results for ORR, PFS, and/or OS in patients receiving pemetrexed in combination with other chemotherapeutic agents and/or radiotherapy were promising in the first-line treatment setting. Pemetrexed was associated with acceptable grade 3-4 hematologic toxicities; it did not result in nonhematologic toxicities commonly seen with cisplatin, such as nephrotoxicity, ototoxicity, and neuropathy. In a single phase III randomized trial, although median OS was longer for patients treated with pemetrexed plus cisplatin (7.3 months) versus cisplatin plus placebo (6.3 months), the difference did not reach statistical significance (P=.082). Results of this review suggest that pemetrexed is an active chemotherapeutic in combination with other agents or radiotherapy in patients with HNC. In particular, the role of pemetrexed as a radiosensitizer and potential alternative to cisplatin warrants investigation. More research is needed to clearly define the role of pemetrexed in HNC treatment.