Induction chronomodulated chemotherapy plus radiotherapy for nasopharyngeal carcinoma: A Phase II prospective randomized study

The aim of this study was to evaluate the efficacy and toxicities of induction chronomodulated chemotherapy in comparison with conventional induction chemotherapy for nasopharyngeal carcinoma (NPC).Between 2003 and 2004, 60 patients with pathologically confirmed NPC were included and randomly assigned to two groups. Patients in the chronomodulated chemotherapy group (n = 30, CC group) received cisplatin at 80 mg/m2 through intravenous infusion from 10:00 to 22:00 and 5-fluorouracil (5-FU) at 1000 mg/m2 plus citrovorum factor at 200 mg/m2 from 22:00 to 10:00 each day for 3 days. Patients in the routine chemotherapy group (n = 30, RC group) received cisplatin infusion within 1 h and 5-FU infusion for about 24 h. The dose in the RC group was the same as that in the CC group. The total irradiation dose in each group was 70 Gy for the whole nasopharynx.One month after induction chemotherapy, the overall response rate was 96.7% in the CC group versus 73.3% in the RC group (P = 0.011). By the end of the 10-year follow-up, 11 patients (36.7%) in the CC group had experienced local recurrence versus 11 patients (36.7%) in the RC group (P > 0.999). The overall survival rates at 1, 5, and 10 years were 96.7%, 53.3%, and 43.3%, respectively, in the CC group, and 96.7%, 43.3%, and 33.3%, respectively, in the RC group (P = 0.346). During induction chemotherapy, the incidence rates of leukocytopenia (43.3% vs. 80%, P = 0.003), thrombocytopenia (26.7% vs. 56.7%, P = 0.018), and nausea/vomiting (40% vs. 66.7%, P = 0.038) were significantly lower in the CC group than in the RC group. The incidence of radiation-induced complications was similar in these two groups.Compared with conventional chemotherapy, induction chrono-chemotherapy seemed to reduce chemotherapy-related toxicities and improve average local relapse time in patients treated with combined chemoradiotherapy for NPC.