Phase I trial of nedaplatin chemotherapy concurrent with radiotherapy for untreated locoregionally advanced nasopharyngeal carcinoma.

Purpose: In this phase I study, single-agent chemotherapy was conducted in patients with locoregionally advanced nasopharyngeal carcinoma (NPC) using nedaplatin (NDP) and concomitant radiotherapy. The study sought to determine the maximum tolerated dose (MTD), recommended dose (RD) and the clinical efficacy of this treatment in locoregionally advanced NPC patients.

Experimental Design: Twenty patients were enrolled. The eligibility criteria included local advanced NPC (stage III or IVa) without any previous treatment and an expected survival of ≥ 3 months. The regimen consisted of 1.8-2.0 Gy daily radiation for 5 days a week and NDP with dose escalation of 70-100 mg/m(2) on day 1. The cycles were repeated every 21 days (day 1, day 22 and day 43) until the completion of chemoradiation. Dose-limiting toxicities (DLTs) included: grade 4 anemia; grade 4 neutropenia lasting for ≥ 5 days; grades 3 and 4 febrile neutropenia; grade 4 thrombocytopenia; grades 3-4 non-hematological toxicity (with the exception of alopecia, nausea) and any of the grade 5 responses.

Results: Ninety-five percent of the assessed patients experienced a treatment response. The median time to progression among all patients was 41.9 months. Two-year overall survival was 95%, while the progression-free survival was 85%. DLT included febrile neutropenia of grade 3. The RD of NDP was 90 mg/m(2) during cycles 1-3.

Conclusion: NDP combined with radiotherapy and administered every 21 days for three cycles was active in patients with locoregionally advanced NPC. The regimen resulted in mild adverse effects and good patient compliance. Based on the findings from the study, the RD of NDP for phase II trial was found to be 90 mg/m(2).