title: Pemetrexed disodium in recurrent locally advanced or metastatic squamous cell carcinoma of the head and neck.
abstract: 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.
authors.affiliation: Centre Antoine Lacassagne, Nice, France.
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.forename: E
authors.initials: E
authors.lastname: Raymond
authors.forename: B
authors.initials: B
authors.lastname: Laguerre
authors.forename: M
authors.initials: M
authors.lastname: Degardin
authors.forename: L
authors.initials: L
authors.lastname: Cals
authors.forename: J P
authors.initials: JP
authors.lastname: Armand
authors.forename: J L
authors.initials: JL
authors.lastname: Lefebvre
authors.forename: D
authors.initials: D
authors.lastname: Gedouin
authors.forename: V
authors.initials: V
authors.lastname: Ripoche
authors.forename: L
authors.initials: L
authors.lastname: Kayitalire
authors.forename: C
authors.initials: C
authors.lastname: Niyikiza
authors.forename: R
authors.initials: R
authors.lastname: Johnson
authors.forename: J
authors.initials: J
authors.lastname: Latz
authors.forename: M
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005260:Female; D005493:Folic Acid Antagonists / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D005971:Glutamates / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006147:Guanine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D009503:Neutropenia / Q000139:chemically induced; D000068437:Pemetrexed; D012074:Remission Induction; D013921:Thrombocytopenia / Q000139:chemically induced
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D005493:Folic Acid Antagonists; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine