Background & objective: Concurrent chemoradiotherapy has definite effect on local-regionally advanced nasopharyngeal carcinoma (NPC). Paclitaxel is confirmed by clinical trail to be one of the most effective single drugs for NPC. This study was to define the maximal tolerant dose (MTD) of paclitaxel in weekly paclitaxel with concurrent intensity-modulated radiotherapy (IMRT) for local-regionally advanced NPC.
Methods: Naive patients with locally advanced NPC were enrolled into this dose-escalating study. Adverse events were graded according to Common Terminology Criteria for Adverse Events version 3.0 (CTCAE v3.0). Primary end points were determined by dose-limiting toxicity (DLT). The starting dose of paclitaxel was 30 mg.(m(2).w)(-1), with a subsequent dose escalation of 10 mg.(m(2).w)(-1). IMRT was given to the nasopharynx and the upper neck; the lower neck was treated by a single anterior field irradiation. The prescription dose was 68 Gy by 30 fractions to the nasopharynx gross tumor, and 60-66 Gy by 30 fractions to the positive neck lymph nodes.
Results: From Apr. 2004 to Sep. 2004, 15 patients received complete chemoradiotherapy, and all of them were eligible for toxicity evaluation. On the first two dose levels of 30 mg.(m(2).w)(-1) and 40 mg.(m(2).w)(-1), no patient experienced DLT. On the next dose level of 50 mg.(m(2).w)(-1), 1 patient experienced DLT of grade 3 mucositis for 4 weeks, and among the additional 3 patients no one developed DLT. On the forth dose level of 60 mg.(m(2).w)(-1), all the patients developed grade 3 mucositis for more than 3 weeks, and the dose-escalating trial stopped. All of the 15 patients achieved clinical complete remission (CR) in the local site; 14 (93.3%) achieved CR in the regional site, and 1 achieved partial remission (PR) and got CR 1 month later. After a median follow-up of 20 months, 1 patient developed multiple bone metastases, and 14 kept disease-free.
Conclusion: The MTD of paclitaxel in weekly paclitaxel with concurrent IMRT for local-regionally advanced NPC is 50 mg.(m(2).w)(-1), with mucositis as DLT.