Result of two randomized trials comparing nolatrexed (Thymitaq (TM)) versus methotrexate in patients with recurrent head and neck cancer

We report on two randomized trials performed in the USA and Europe, which c ompared methotrexate and nolatrexed as treatment for patients with recurren t head and neck cancer. Eligibility criteria included: histologically confi rmed squamous-cell carcinoma, measurable disease, adequate hematological, r enal and hepatic functions, failure of a first-line chemotherapy, and infor med consent. Methotrexate 40 mg/m(2) was weekly given by short infusion, an d nolatrexed 725 mg/m(2) 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 nolatre xed and methotrexate, respectively. Patient characteristics included 115 ma les and 24 females; median age 60 years. In the nolatrexed arm, the followi ng 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 g rade 3-4 toxicities were neutropenia (7.1%) and mucositis (6.9%). There was no difference in activity between the nolatrexed and the methotrexate trea tment: 3.3% and 10.8% of objective responses, 1.9 versus 1.5 months of dise ase-free progression and 3.5 versus 3.7 months of overall survival, respect ively. Nolatrexed has demonstrated a similar activity to methotrexate.