5-fu continuous pump infusion via superficial temporal artery cannula for high T-staged nasopharyngeal cancinoma: A phase I clinical trial.

Background: To present the maximum tolerated dose(MTD) , safety, and efficacy of 5-Fu continuously pump infusion via superficial temporal artery cannula for high T staged nasopharyngeal cancinoma. Methods: 29 patients with histologically confirmed nasopharyngeal cancinoma were eligible in the phase I trial. They received induction chemotherapy which consisted of cisplatin (20 mg/m2/d , days 1-5) and 5-FU(pump infused continuously for 120 hours in different dose gradient), while the regimen was administrated via superficial temporal artery. The MTD of 5-Fu was determined by detecting increasing doses in different groups until the highest dose with acceptable toxicities were obtained. Dose-limiting toxicity (DLT) was defined as any grade 4 or more serious toxicity, and the trial was closed when the rate of DLT exceeded 25%. The total length of the chemotherapy cycle was 21 days. Followed with 2 circles chemotherapy, the radical radiotherapy was conducted. We assessed efficacy, toxicity and life quality, especially on the oral mucositis and radiation brain damage. Results: There were six dose gradients of 5-Fu, including 200mg/m2(6 cases), 250mg/m2(6 cases), 300mg/m2(5 cases), 350mg/m2(5 cases), 400mg/m2(5 cases),450mg/m2 (5 cases)and 500mg/m2(2 cases). No toxicities of grade III or above was observed in the group with dose of not exceeding 350 mg/m2. In the group of 400mg/m2, there were 2 patients developed grade III oral mucositis. And 1 cases was found with grade IV toxicity in the 450mg/m2 group. The 2 patients enrolled in the group of 500mg/m2 all were observed the grade IV toxicity mainly included oral mucositis, so the test was terminated. The overall response rates for the primary mass and lymph nodes were 93% and 100%, respectively. The 5-year overall survival (OS) was 80%. The 5-years progression-free-survival(PFS) was 73.3%. The MTD of 5-Fu was 450mg/m2, we also determined the optimal dose was 400mg/m2 according to the response, toxicities and survival. Conclusions: 5-Fu continuously pump infusion via superficial temporal artery cannula results in promising efficacy and tolerability in patients with high T staged nasopharyngeal cancinoma, the MTD was 450mg/m2.