Phase II trial of cisplatin, 5-fluorouracil and folinic acid using a weekly 24-h infusion schedule for locally advanced head and neck cancer: a pharmacokinetic and clinical survey.

The objective of this phase II prospective study was to determine the efficacy and the toxicity of a new schedule of neoadjuvant chemotherapy in locally advanced squamous cell carcinomas of the head and neck (SCCHN). Thirty-three patients were included in this study (13 stage III and 20 stage IV). Cisplatin (CDDP: 35 mg/m2), 5-fluorouracil (FU: 2 g/m2) and folinic acid (FA: 500 mg/m2) were administered by continuous i.v. infusion for 24 h, once every 7 days. Six cycles of neoadjuvant chemotherapy were planned before definitive locoregional treatment. A total of 195 cycles were analysed for toxicity: mucositis was observed in 11/195 cycles; 12/195 showed diarrhea and vomiting occurred in 10/195. The myelosuppression was low (neutropenia: 4/195, thrombopenia: 3/195). One treatment-related death was observed after grade IV neutropenia at the fourth cycle. Thirty-two patients were evaluated for response. The objective response rate was 87%, with 50% complete response (CR) and 37% partial response. Failure rate was 13% (stable disease). There was no progressive disease. Survival and DFS duration were significantly higher in cases of CR or in laryngeal localization. The average peak plasma levels for the 6 courses of CDDP, 5-FU, dl-FA and mTHF were 4.9+/-0.76 microM, 4.1+/-0.54 microM, 29.1+/-2.4 microM and 4.8+/-0.31 microM respectively. Therefore, the administration of the 3 drugs by a 24 h continuous i.v. infusion reached an efficient level for drug modulation. This new weekly schedule is as active as other standard therapy in the disease but significantly less toxic as neoadjuvant chemotherapy in advanced untreated SCCHN. With the low toxicities observed with this schedule, additional treatment (surgery and/or radiotherapy) is warranted to evaluate the impact on overall survival of SCCHN.