Radiation therapy concurrent with weekly paclitaxel for locoregionally advanced nasopharyngeal carcinoma: outcomes of a phase I trial.

Purpose: The purpose of this study was to define the maximum tolerated dose (MTD) by describing the dose-limiting toxicity (DLT) of paclitaxel given as a 3-hour intravenous infusion concurrently with conventional radiotherapy in patients with locoregionally advanced nasopharyngeal carcinoma (NPC).
Materials and Methods: Patients with locoregionally advanced NPC were enrolled into a dose-escalating study. Toxicity was graded according to Common Toxicity Criteria 2.0. MTD was defined when 2 of 6 patients developed DLT. The starting dose of paclitaxel was 20 mg/m2 once weekly, with a subsequent dose escalation of 10 mg/m2 in cohorts of 3 new patients. Radiation therapy was administered in a conventional technique over 7 weeks in 2.0-Gy/daily fractions for 5 days/wk up to total doses of 68-70 Gy.
Results: From November 2000 to June 2001, 16 patients completed chemoradiotherapy. On the first-dose level (20 mg/m2), no patient experienced DLT. On the next dose level with 30 mg/m2, 1 patient experienced DLT with grade 3 mucositis, which lasted for 5 weeks, and among the additional 3 patients, no one developed DLT. On the third dose level with 40 mg/m2, 1 patient developed grade 3 mucositis and another grade 3 dermatitis, and both of them lasted more than 3 weeks. To make the trial more credible, another 4 patients were added to the 30-mg/m2 level, and no DLT occurred. Thus, the accrual of patients stopped.
Conclusion: Combined modality with paclitaxel given weekly, as a 3-hour infusion concomitant to conventional radiotherapy, is feasible for locoregionally advanced NPC. The dose recommended for a phase II trial is 30 mg/m2 with mucositis and dermatitis as DLT, and other toxicity is mild.