Induction chemotherapy followed by radiotherapy versus radiotherapy alone in patients with advanced nasopharyngeal carcinoma: Results of a matched cohort study

BACKGROUND. Prospective randomized and retrospective studies on adjunctive chemotherapy in patients with advanced locoregional nasopharyngeal carcinoma have yielded conflicting results and the role of chemotherapy in this disease had not been clearly defined. The authors report the results of a single institution, matched cohort study comparing a group of 61 patients with advanced stage nasopharyngeal carcinoma treated with induction chemotherapy followed by radiation therapy with a matched group treated with radiotherapy alone. METHODS. Between 1985 and 1992, 61 patients with advanced locoregional nasopharyngeal carcinoma received induction chemotherapy [cisplatin, 100 mg/m² on Day 1 and 5-fluorouracil [5-FU], 1000 mg/m², on Days 1-5) for 3 cycles followed by definitive radiation therapy (CT/RT group). This group was matched with a group of 61 patients from a population of 378 patients who received radiation therapy alone (RT group). Matching characteristics were T classification, N classification, histology, and level of cervical lymph node metastases. These characteristics were found to be significant determinants of distant metastasis (DM) and/or survival in a multivariate analysis that was performed in the entire radiotherapy group. Radiation therapy consisted of 66-72 gray in 6.5 to 7 weeks in both groups. Fifty-nine patients (97%) in both groups had Stage IV disease. Fifteen patients (25%) in both groups had lower cervical lymph node metastases. The tumor histologic types also had similar distribution in both groups. Median follow-up time among surviving patients of the CT/RT group was 4.9 years (range, 1.3-9.8 years). RESULTS. The 5-year cumulative incidence of DM was 19 ± 5% for the CT/RT group and 34 ± 6% for the RT alone group (P = 0.019; log rank test). This reduction in distant failure was more prominent in patients with intermediate (N2-N3 disease; upper or midcervical lymph nodes), or high risk (N2-N3 disease; lower cervical lymph nodes) of DM. This reduction in DM translated into improvement in disease free survival (DFS) and overall survival (OS). The 5- year actuarial DFS rates were 64 ± 6% for the CT/RT group compared with 42 ± 7% for the RT group (P = 0.015). The 5-year actuarial OS rates were 69 ± 6% (CT/RT group) and 48 ± 7% (RT group), respectively (P = 0.012). The incidence of locoregional failure was slightly lower in the CT/RT group, but this difference did not reach statistical significance. There was no significant difference in the incidence and severity of acute mucositis between the two groups during radiotherapy. The 5-year cumulative incidence of Grade 3 or higher late complications was also similar in both groups (5 ± 3% in the CT/RT group and 8 ± 3% in the RT group; P = 0.721). CONCLUSIONS. This matched cohort study provides additional evidence that induction cisplatin-5-FU chemotherapy prior to definitive radiation improves freedom from distant metastasis, DFS, and OS for patients with locoregional Stage IV nasopharyngeal carcinoma without increasing treatment-related morbidity.