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

• Published in: British journal of cancer Vol. 85; no. 5; pp. 649 - 655
• Main Authors: PIVOT, X, RAYMOND, E, NIYIKIZA, C, JOHNSON, R, LATZ, J, SCHNEIDER, M, LAGUERRE, B, DEGARDIN, M, CALS, L, ARMAND, J. P, LEFEBVRE, J. L, GEDOUIN, D, RIPOCHE, V, KAYITALIRE, L
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-09-2001
• Subjects: Adult; Aged; Antineoplastic agents; Antineoplastic Agents - adverse effects; Antineoplastic Agents - pharmacokinetics; Antineoplastic Agents - therapeutic use; Biological and medical sciences; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - mortality; Carcinoma, Squamous Cell - secondary; Chemotherapy; Enzyme Inhibitors - adverse effects; Enzyme Inhibitors - pharmacokinetics; Enzyme Inhibitors - therapeutic use; Female; Folic Acid Antagonists - adverse effects; Folic Acid Antagonists - pharmacokinetics; Folic Acid Antagonists - therapeutic use; Glutamates - adverse effects; Glutamates - pharmacokinetics; Glutamates - therapeutic use; Guanine - adverse effects; Guanine - analogs & derivatives; Guanine - pharmacokinetics; Guanine - therapeutic use; Head and Neck Neoplasms - drug therapy; Head and Neck Neoplasms - mortality; Head and Neck Neoplasms - pathology; Humans; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - drug therapy; Neoplasm Recurrence, Local - mortality; Neutropenia - chemically induced; Pemetrexed; Pharmacology. Drug treatments; Regular; Remission Induction; Thrombocytopenia - chemically induced; Antineoplastic agent; Human; Squamous cell carcinoma; Toxicity; Treatment efficiency; Malignant tumor; Recurrent; Pemetrexed; Biological activity; Antifolate; Chemotherapy; Treatment; Phase II trial; Head and neck; ENT disease; Complication; Advanced stage; Pharmacokinetics
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1054/bjoc.2001.2010

This phase II study determined response rate of patients with locally advanced or metastatic head and neck cancer treated with pemetrexed disodium, a new multitargeted antifolate that inhibits thymidylate synthase, dihydrofolate reductase and glycinamide ribonucleotide formyl transferase. 35 patients with local or metastatic relapse of squamous cell carcinoma of the head and neck (31 male, 4 female; median age 53 years) were treated with pemetrexed 500 mg m(2)administered as a 10-minute infusion on day 1 of a 21-day cycle. 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 survival was 6.4 months (range 0.7-28.1 months; 95% CI: 3.9-7.7 months). 24 patients (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%) and 6 (17.1%) patients, respectively. The most frequent non-haematological toxicity was grade 3/4 mucositis (17.1%; 6 patients). In conclusion, pemetrexed is active in squamous cell carcinoma of the head and neck. Although substantial haematological toxicities were experienced by patients, subsequent studies have shown that these toxicities can be proactively managed by folic acid and vitamin B(12)supplementation.