Objective:The purpose of this study was to define the maximum tolerated dose(MTD) by describing the doselimiting toxicity(DLT) of weekly cisplatin concurrently with conventional plus 3-dimensional conformal radiotherapy(CT + 3DCRT) in patients with loco-regionally advanced nasopharyngeal carcinoma(NPC).Methods:Patients with loco-regionally advanced NPC(III/IVa stage) were enrolled into a dose-escalating study.Toxicity was graded according to Common Terminology Criteria for Adverse Events version 3.0(CTCAE v3.0).MTD was defined when 2 of 6 patients developed DLT.The starting dose of cisplatin was 15 mg/m2/w,with a subsequent dose escalation of 5 mg/m2/w in cohorts of 3 new patients.CT + 3DCRT was given to the nasopharynx and the upper neck;the lower neck was treated by a single anterior field irradiation.The prescription dose was 70-80 Gy by 35-40 fractions to the nasopharynx gross tumor,and 66-70 Gy by 33-35 fractions to the positive neck lymph nodes.Results:From Jun.2008 to Sep.2009,24 patients received complete chemoradiotherapy,and all of them were eligible for toxicity evaluation.On the first five dose levels of 15 mg/m2/w and 35 mg/m2/w,no patient experienced DLT.On the next dose level of 40 mg/m2/w,1 patient experienced DLT of grade 3 myelosuppression for 1.4 weeks,and among the additional 3 patients,no one developed DLT.On the seventh dose level of 45 mg/m2/w,all the patients developed grade 3 myelosuppression for more than 1 weeks,and the dose-escalating trial stopped.The 23(95.8%) patients achieved clinical complete remission(CR) in the local site;22(91.7%) achieved CR in the regional site,and all patients got CR 3 months later.After a median follow-up of 16.4 months,1 patient developed liver metastases 2 months later,1 patient developed bone metastases 10 months later and 22 kept disease-free survival.Conclusion:The MTD of cisplatin weekly with concurrent CT + 3DCRT for local advanced NPC is 40 mg/m2/w,with myelosuppression as DLT.
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