title: Result of two randomized trials comparing nolatrexed (Thymitaq) versus methotrexate in patients with recurrent head and neck cancer.
abstract: We report on two randomized trials performed in the USA and Europe, which compared methotrexate and nolatrexed as treatment for patients with recurrent head and neck cancer. Eligibility criteria included: histologically confirmed squamous-cell carcinoma, measurable disease, adequate hematological, renal and hepatic functions, failure of a first-line chemotherapy, and informed consent. Methotrexate 40 mg/m2 was weekly given by short infusion, and nolatrexed 725 mg/m2 per day was administered as a five-day continuous infusion, every three weeks. A total of 139 patients (63 in the USA. 76 in Europe) were randomized based on a ratio of 2/1: 93 and 46 received nolatrexed and methotrexate, respectively. Patient characteristics included 115 males and 24 females; median age 60 years. In the nolatrexed arm, the following grade 3-4 toxicities occurred: neutropenia (29.9%) with 3.1% of febrile neutropenia, mucositis (33.3%), and vomiting (10.3%). In the MTX arm, the grade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate treatment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of disease-free progression and 3.5 versus 3.7 months of overall survival, respectively. Nolatrexed has demonstrated a similar activity to methotrexate.
authors.affiliation: Centre Antoine Lacassagne, Nice, France. xpivot@chu-besancon.fr
authors.forename: X
authors.initials: X
authors.lastname: Pivot
authors.forename: S
authors.initials: S
authors.lastname: Wadler
authors.forename: C
authors.initials: C
authors.lastname: Kelly
authors.forename: R
authors.initials: R
authors.lastname: Ruxer
authors.forename: J
authors.initials: J
authors.lastname: Tortochaux
authors.forename: J
authors.initials: J
authors.lastname: Stern
authors.forename: D
authors.initials: D
authors.lastname: Belpomme
authors.forename: Y
authors.initials: Y
authors.lastname: Humblet
authors.forename: C
authors.initials: C
authors.lastname: Domenge
authors.forename: N
authors.initials: N
authors.lastname: Clendeninn
authors.forename: A
authors.initials: A
authors.lastname: Johnston
authors.forename: C
authors.initials: C
authors.lastname: Penning
authors.forename: M
authors.initials: M
authors.lastname: Schneider
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D003967:Diarrhea / Q000139:chemically induced; D004791:Enzyme Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D006258:Head and Neck Neoplasms / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000009:adverse effects / Q000627:therapeutic use*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009503:Neutropenia / Q000139:chemically induced; D011799:Quinazolines / Q000009:adverse effects / Q000627:therapeutic use*; D013940:Thymidylate Synthase / Q000037:antagonists & inhibitors; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D004791:Enzyme Inhibitors; D011799:Quinazolines; D013940:Thymidylate Synthase; C099178:nolatrexed; D008727:Methotrexate