Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck

This phase II study determined response rate of patients with locally advan ced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofol ate reductase and glycinamide ribonucleotide formyl transferase. 35 patient s with local or metastatic relapse of squamous cell carcinoma of the head a nd neck (31 male, 4 female; median age 53 years) were treated with pemetrex ed 500 mg m(2) administered as a 10-minute infusion on day 1 of a 21-day cy cle. Patients received 1 to 8 cycles of therapy. 9 patients (26.5%) had an objective response, with a median response duration of 5.6 months (range 2. 9-20 months). 15 (44.1%) had stable disease, and 8 (23.5%) had progressive disease. 2 patients were not assessable for response. Median overall surviv al was 6.4 months (range 0.7-28.1 months; 95% CI: 3.9-7.7 months). 24 patie nts (68.6%) experienced grade 3/4 neutropenia, with febrile neutropenia in 4 (11.4%). Grade 3/4 anaemia and thrombocytopenia occurred in 11 (34.3%) an d 6 (17.1%) patients, respectively. The most frequent non-haematological to xicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrex ed is active in squamous cell carcinoma of the head and neck. Although subs tantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by foli c acid and vitamin B-12 supplementation. (C) 2001 Cancer Research Campaign.