Radiotherapy Concurrent With Weekly Cisplatin For Locoregionally Advanced Nasopharyngeal Carcinoma: Outcomes Of A Dose Escalating Study

OBJECTIVE: This study was to define the maximal tolerant dose of cisplatin in weekly cisplatin with concurrent conventional plus three conformal radiotherapy ( CT+3DCRT) for locally advanced NPC, and explore the changes of T cell subtypes of locally advanced nasopharyngeal carcinoma (NPC) during concurrent chemoradiotherapy.METHODS: Patients according to Common Terminology Criteria for adverse Events version 3.0 (CTCAE v3.0). Primary endpoints were determined by dose limiting toxicity(DLT). The starting dose of cisplatin was 15mg·(m²Â·w)^-1, with a subsequent dose escalation of 5mg·(m²Â·w)^-1. 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 66～76Gy by 33～38 fractions to the nasopharynx gross tumor , median dose 72.5Gy ,and 66～76Gy by 33～38fractions to the positive neck lymph nodes, median dose 70Gy, and50～60Gy by 25～30 fractions to the negative neck lymph nodes,median dose 55Gy. T cell subtypes of NPC patients were detected by flow cytometry before treatment , in the fourth and seventh week.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 from 15mg·(m²Â·w)^-1 to 35mg·(m²Â·w)^-1, no patient experienced DLT. On the next dose level of 40mg·(m²Â·w)^-1, 1 patient experienced DLT of grade 3 myelosuppression for 1.4 weeks, and among the additional 3 patients no one developed DLT. One the next dose level of 45mg·(m²Â·w)^-1, All the patients developed grade 3 myelosuppression for more than 1 weeks, and the dose-escalating trial stopped. The maximal tolerant dose of cisplatin in weekly cisplatin with concurrent conventional plus three conformal radiotherapy ( CT+3DCRT) for locally advanced NPC is 40mg·(m²Â·w)^-1, No one experienced grade 4 adverse events. There were no treatment-related deaths . and all patients got CR 3 month later .T cell subtypes of locally advanced NPC were dynamic changes during concurrent chemoradiotherapy. CD4 significantly decreased(p<0.01),CD8 slightly increased (p>0.25)and CD4/CD8 ration decreased in fourth week during treatment. CD4 slightly decreased(p>0.25),CD8 significantly increased (p<0.05)and CD4/CD8 ration decreased continually in seventh week during treatment. CD4/CD8 ration increased on the two dose levels from 15～20mg·(m²Â·w)^-1 in the seventh week,compared with patients the fourth week. CD4/CD8 ration decreased continually on the five dose levels from 25～45mg·(m²Â·w)^-1.CONCLUSION: The maximal tolerant dose of cisplatin in weekly cisplatin with concurrent CT+3DCRT for locally advanced NPC is 40mg·(m²Â·w)^-1, with myelosuppression as DLT.There are dynamic changes of T cell subtypes in NPC patients during treatment:CD4/CD8 ration decreased in fourth week during treatment. CD4/CD8 ration increased on the two dose levels from 15～20mg·(m²Â·w)^-1 in the seventh week,compared with patients the fourth week. CD4/CD8 ration decreased continually on the five dose levels from 25～45mg·(m²Â·w)^-1. These results are beneficial to clinical reasonable immune modulating treatment.