International randomized phase 2 study on the addition of docetaxel to the combination of cisplatin and 5-fluorouracil in the induction treatment for nasopharyngeal carcinoma in children and adolescents

Purpose: Nasopharyngeal carcinoma (NPC) is a rare but aggressive malignancy in children and adolescents. An international, randomized phase 2 trial was conducted to compare induction chemotherapy with docetaxel plus cisplatin and 5-fluorouracil (TPF) with cisplatin and 5-fluorouracil (PF) in NPC patients under the age of 21. Methods: Patients with stage IIB-IV NPC were randomly assigned, in a 2:1 ratio, to receive TPF or PF 3-weekly for three cycles, followed by chemoradiotherapy. The primary endpoint was the complete response rate achieved with TPF or PF. Docetaxel pharmacokinetics was also evaluated. Results: Seventy-five patients (median 16 years old) were randomized, with 50 assigned to the TPF group and 25 to the PF group. Overall response was assessed after induction treatment: one patient in the TPF group and none in the PF group had a complete response. Partial response was achieved in 76.0 and 80.0 % in the TPF and PF groups, respectively. The overall safety profile was consistent with findings in adults. The estimated 3-year overall survival rate was 78.0 % for the PF group and 85.7 % for the TPF group (median follow-up 3.3 years). Mean docetaxel area under the curve was 3.41 μg h/mL, compared with 3.51 μg h/mL seen in adult patients. Conclusion: This study demonstrated the feasibility of prospective randomized protocols, even for such rare tumors as pediatric NPC. Overall, there were no differences between the two treatment arms in terms of efficacy and toxicity. The pharmacokinetics of docetaxel in pediatric patients at 75 mg/m² was similar to those observed in adults.