OBJECTIVE: A phase I clinical trial was conducted to investigate the effective dose of induction chemotherapy in combination with concurrent intensity-modulated radiotherapy for the treatment of locally advanced nasopharyngeal carcinoma.
MATERIALS AND METHODS: Patients with stage III, IVa and IVb (2002 UICC stage) primary nasopharyngeal carcinoma were enrolled and given induction chemotherapy with Docetaxel 60 mg/m2 day1, DDP 60 mg/m2 day1 and 5-Fu for 120 h by intravenous infusion at an initial dose of 450 mg/(m2?day). The initial dose of 450 mg/(m2?day) was escalated by 50 mg/(m2?day) every 3 weeks for 3 courses. Intensity-modulated radiotherapy (IMRT) was given after 3 weeks of the third course of chemotherapy, and the concurrent chemotherapy was DDP single agent 80 mg/m2 every three weeks for 2-3 courses. The GTV of the primary site of intensity-modulated radiotherapy was outlined in two parts, GTVpost-IC was outlined according to the size of the tumor visible on imaging after induction chemotherapy, GTV pre-post-IC was the area of original tumor invasion and tumor regression after induction chemotherapy, 68 Gy and 63 Gy were given respectively, and 60 Gy and 54 Gy were given to the high clinical risk area (CTV60) and low risk area (CTV54). The maximum-tolerated dose (MTD) of 5-Fu was determined in the phase I clinical trial, and the local tumor control, distant metastasis and normal tissue toxicity were further observed in the phase II clinical trial with this modality.
RESULTS: A total of 30 patients completed treatment from November 2007 to July 2009. Among them, the dose of TPF-induced chemotherapy regimen was determined by treating 12 patients: Docetaxel 60 mg/m2 day1, DDP 60 mg/m2 day1, 5-Fu 550 mg/(m2?day) day1-5, 120h intravenous infusion. Dose-limiting toxicity (DLT) was manifested by mucosal reactions and diarrhea. A total of 24 patients were treated at this dose level, including 12 patients in stage III, 5 patients in stage IVa and 7 patients in stage IVb. 22 patients completed 3 courses of induction chemotherapy, 2 patients completed only 1 course of induction chemotherapy due to chemotherapy toxicity, and all patients completed concurrent radiotherapy as planned. 91.6% of the 3 courses of induction chemotherapy were completed, and the overall response rate of induction chemotherapy was 100%. The complete remission rate of nasopharyngeal lesions and cervical lymph nodes reached 31.8% (7/22), and the complete remission rate of nasopharyngeal lesions and cervical lymph nodes reached 81.8% at the end of concurrent radiotherapy. No delay in radiotherapy was seen with induction chemotherapy, and induction chemotherapy did not aggravate the toxic effects of concurrent radiotherapy. After a median follow-up period of 9 months, 22 patients had 100% local regional control and no distant metastases were observed.
CONCLUSIONS: TPF induction chemotherapy regimen in patients with locally advanced nasopharyngeal carcinoma has a high near-term response rate, with tolerable chemotherapy-related toxicity and dose-limiting toxicity of mucosal and diarrheal reactions. The combination of TPF with concurrent intensity-modulated radiotherapy had good near-term efficacy in the treatment of locally advanced nasopharyngeal carcinoma, and induction chemotherapy did not aggravate the toxic effects of concurrent radiotherapy.