Preliminary report of the Asian-Oceanian Clinical Oncology Association randomized trial comparing cisplatin and epirubicin followed by radiotherapy versus radiotherapy alone in the treatment of patients with locoregionally advanced nasopharyngeal carcinoma. Asian-Oceanian Clinical Oncology Association Nasopharynx Cancer Study Group

BACKGROUND: The aim of this trial was to compare the outcome achieved with neoadjuvant chemotherapy followed by radiotherapy to that achieved with radiotherapy alone for patients with locoregionally advanced undifferentiated or poorly differentiated nasopharyngeal carcinoma (NPC) meeting one of the following criteria: Ho's T3 disease, Ho's N2-N3 disease, or lymph node size > or =3 cm. METHODS: Between September 1989 and August 1993, 334 patients were enrolled in the study, with equal numbers of patients randomized to the neoadjuvant chemotherapy arm (CT arm) and the radiotherapy arm (RT arm). Neoadjuvant chemotherapy consisting of 2-3 cycles of cisplatin (60 mg/m2 on Day 1) and epirubicin (110 mg/m2 on Day 1) followed by radiotherapy was given to the CT arm. For radiotherapy, a dose of 66-74 gray (Gy) (median, 71 Gy) was delivered to the primary tumor and 60-76 Gy (median, 66 Gy) to the neck. Two hundred eighty-six eligible patients completed the treatment and were evaluable for treatment response (134 in the CT arm, 152 in the RT arm). All patients were included in the survival analysis based on the intention to treat. The median follow-up was 30 months for the whole cohort and 41 months for the surviving patients. RESULTS: Analysis of the 334 patients based on the intention to treat showed no significant difference in relapse free survival (RFS) or overall survival (OS) between the 2 treatment arms (3-year RFS rate: 48% in the CT arm vs. 42% in the RT arm, P = 0.45; 3-year OS rate: 78% vs. 71%, P = 0.57). In an efficacy analysis based on only the 286 evaluable patients, a trend of improved RFS favoring the CT arm was observed (3-year RFS rate: 58% vs. 46%, P = 0.053), with again no significant difference in OS (3-year OS rate: 80% vs. 72%, P = 0.21). In the subgroup of 49 patients with bulky neck lymph nodes >6 cm, improved RFS (3-year RFS rate: 63% vs. 28%, P = 0.026) and OS (3-year OS rate: 73% vs. 37%, P = 0.057) were observed, favoring the CT arm. CONCLUSIONS: This multicenter randomized study did not demonstrate any benefit with the addition of cisplatin-epirubicin neoadjuvant chemotherapy for patients with locoregionally advanced nasopharyngeal carcinoma; therefore routine administration of neoadjuvant chemotherapy to this target group cannot be recommended. Although the overall incidence of recurrence was reduced with the addition of chemotherapy in the efficacy analysis, the overall survival was not affected. A more effective chemotherapy regimen, the selection of an appropriate target group, and the use of an alternative strategy for combining chemoradiotherapy should be explored in future trials.