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 (Platinol), raltitrexed (Tomudex, investigational in the United States), levofolinic acid, and 5-fluorouracil (5-FU), compared with cisplatin, methotrexate, levofolinic acid, and 5-FU.
SAN FRANCISCOInterim 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 (Platinol), raltitrexed (Tomudex, investigational in the United States), levofolinic acid, and 5-fluorouracil (5-FU), compared with cisplatin, 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.
Dr. Caponigro noted that with 58 patients currently in arm A (with 47 evaluable), the overall response rate is at 74% and the complete response rate is 20%, with both hematologic and non-hematologic toxicities remaining comparable between the arms (neutropenia 71% for arm A, 64% for arm B). Overall response for arm B is at 42% (15 of 36 patients).
While three patients in arm A experienced renal toxicity, none were grade 3-4. In arm B, among the six patients with renal toxicity, one was grade 4 and resulted in death. There was one other toxic death, also in arm B, from grade 4 mucositis.
While characterizing the results as "encouraging," Dr. Caponigro noted that the findings are not generating the same enthusiasm stimulated by the early findings. Final results from the remaining patients and survival data will determine whether or not phase III trials will be conducted.