INDUCTION CHEMOTHERAPY FOLLOWED BY RADIOTHERAPY VERSUS RADIOTHERAPY ALONE IN PATIENTS WITH ADVANCED NASOPHARYNGEAL CARCINOMA - RESULTS OF AMATCHED COHORT STUDY

BACKGROUND. Prospective randomized and retrospective studies on adjunc tive chemotherapy in patients with advanced locoregional nasopharyngea l carcinoma have yielded conflicting results and the role of chemother apy in this disease had not been clearly defined. The authors report t he results of a single institution, matched cohort study comparing a g roup of 61 patients with advanced stage nasopharyngeal carcinoma treat ed with induction chemotherapy followed by radiation therapy with a ma tched group treated with radiotherapy alone. METHODS. Between 1985 and 1992, 61 patients with advanced locoregional nasopharyngeal carcinoma received induction chemotherapy (cisplatin, 100 mg/m(2) on Day 1 and 5-fluorouracil [5-FU], 1000 mg/m(2), on Days 1-5) for 3 cycles followe d by definitive radiation therapy (CT/RT group). This group was matche d with a group of 61 patients from a population of 378 patients who re ceived radiation therapy alone (RT group). Matching characteristics we re T classification, N classification, histology, and level of cervica l lymph node metastases. These characteristics were found to be signif icant determinants of distant metastasis (DM) and/or survival in a mul tivariate 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 m etastases. 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 cu mulative 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 i n distant failure was more prominent in patients with intermediate (N2 -N3 disease; upper or midcervical lymph nodes), or high risk (N2-N3 di sease; lower cervical lymph nodes) of DM. This reduction in DM transla ted into improvement in disease free survival (DFS) and overall surviv al (OS). The 5-year actuarial DFS rates were 64 +/- 6% for the CT/RT g roup 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 grou p), respectively (P = 0.012). The incidence of locoregional failure wa s 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 durin g radiotherapy. The 5-year cumulative incidence of Grade 3 or higher l ate 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 m atched cohort study provides additional evidence that induction cispla tin-5-FU chemotherapy prior to definitive radiation improves freedom f rom distant metastasis, DFS, and OS for patients with locoregional Sta ge IV nasopharyngeal carcinoma without increasing treatment-related mo rbidity. (C) 1997 American Cancer Society.