SAN FRANCISCO—Interim analysis of a clinical trial of patients with inoperable head and neck cancer (locally advanced or metastatic) showed superior response rates for the combination of cisplatin(Drug information on cisplatin) (Platinol), raltitrexed (Tomudex, investigational in the United States), levofolinic acid, and 5-fluorouracil (5-FU), compared with cisplatin, methotrexate(Drug information on methotrexate), levofolinic acid, and 5-FU.
Phase I and II trials of the raltitrexed combination had shown "impressive" activity, with a 100% response rate among 15 patients, said F. Caponigro, MD, National Tumor Institute, Naples, Italy. He presented the results at the 37th Annual Meeting of the American Society of Clinical Oncology (ASCO abstract 920) on behalf of the Southern Italy Cooperative Oncology Group.
In this phase II continuation of those studies, patients with no prior chemotherapy or radiotherapy received cisplatin 60 mg/m² and raltitrexed 2.5 mg/m² on day 1, levofolinic acid 250 mg/m² (leucovorin would be used in the United States), and 5-FU 900 mg/m² on day 2 (arm A), or cisplatin 65 mg/m² and methotrexate 500 mg/m² on day 1, levofolinic acid 250 mg/m² and 5-FU 800 mg/m² on day 2 (arm B).
Both treatments were repeated every 2 weeks. Evaluation for tumor response was performed after four cycles.
When 35 patients had been evaluated in each arm, investigators terminated accrual in arm B after an interim analysis showed significantly better overall and complete response rates in the raltitrexed arm.
At that point, there were 10 complete responses and 18 partial responses in arm A for an overall response rate of 80%. In arm B, 3 complete responses and 11 partial responses were observed for an overall response rate of 40%. Differences were significant at P = .03 and P = .001, respectively.
The main side effect, neutropenia, occurred at the grade 3-4 level in 28 patients on arm A and 32 patients on arm B. Nonhematologic toxicity was mild in both arms.
