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The aim of this study is to evaluate the toxicity and survival of outpatient weekly 24\u2010hour infusion adjuvant chemotherapy for NPC patients with high\u2010risk of distant failure.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods.<\/jats:title><jats:p>Our definition of high\u2010risk NPC included patients with (1) 1992 AJCC staging system of N3, T4N2, or N2 with one of nodal size &gt; 4 cm; (2) supraclavicular node metastasis; and (3) residual disease after radiotherapy or neck relapse. From August 1994 to August 1997, 41 NPC patients matching the preceding criteria agreed to receive weekly PFL (cisplatin 25 mg\/m<jats:sup>2<\/jats:sup>, 5\u2010fluorouracil 1250 mg\/m<jats:sup>2<\/jats:sup>, and leucovorin 120 mg\/m<jats:sup>2<\/jats:sup>) adjuvant chemotherapy for a total of 18 weeks. Clinical data of another 88 patients with similar disease status who did not receive adjuvant chemotherapy during the same period were collected and analyzed for comparison. Survival analysis was investigated by the Kaplan\u2010Meier method and the Cox proportional hazards model.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results.<\/jats:title><jats:p>A total of 700 weekly chemotherapy doses was delivered to 41 patients. The ratio of actual\/planned dose delivery was 94.9%. Grade 3\u20134 toxicity of adjuvant chemotherapy included leucopenia (7.3%), anemia (2.4%), thrombocytopenia (2.4%), and nausea\/vomiting (2.4%). After a median follow\u2010up of 70 months, 26.8% (11 of 41) and 47.7% (42 of 88) of patients in PFL and no adjuvant chemotherapy groups had distant metastasis (<jats:italic>p<\/jats:italic> = .0247). The 5\u2010year metastasis\u2010free survival rates were 71.9% for the PFL group compared with 48.4% for no adjuvant chemotherapy patients (<jats:italic>p<\/jats:italic> = .0187). The 5\u2010year overall survival rates were 53.7% (PFL group) and 38.3% (no adjuvant chemotherapy group), respectively (<jats:italic>p<\/jats:italic> = .0666). Multivariate Cox analysis showed PFL adjuvant chemotherapy was the independent factor that predicted metastasis\u2010free survival after adjustment for other variables.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions.<\/jats:title><jats:p>Outpatient weekly 24\u2010hour continuous infusion PFL adjuvant chemotherapy is a well\u2010tolerated regimen with promising results in high\u2010risk NPC patients and merits investigation in phase III studies. \u00a9 2003 Wiley Periodicals, Inc. 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