Distant metastasis has become the most frequent failure site-more so than locoregional relapse-after adequate radiotherapy in nasopharyngeal carcinoma (NPC). A prospective study was initiated to test the role of postradiation adjuvant chemotherapy using a weekly schedule for selected patients with high-risk NPC (N3, T4N2b-2c, and N2b-2c, with one of nodal size > 4 cm, or residual disease after radiotherapy). Through July 1993 to August 1994, a total of 20 patients were entered into the study: 16 men and four women, with a median age of 49 years and age range of 27-75 years. Pathology showed WHO type I:II:III = 2:13:5. Previous treatment consisted of concurrent chemoradiotherapy (16 patients), radiotherapy alone (two), and neoadjuvant chemotherapy followed by radiotherapy (two). Postradiation adjuvant chemotherapy was usually started 2 months after radiotherapy, using a weekly FP schedule (5-fluorouracil 1,250 mg/m2 + cisplatin 25 mg/m2, mixed in 100 ml saline, 24 h continuous i.v. infusion) for 18 weeks. The treatment of five patients was at 5, 6, 10, 14, and 15 weeks because of leukopenia-induced mortality, sudden death unrelated to adjuvant chemotherapy, a patient's refusal, and distant metastasis (the last two cases) during adjuvant chemotherapy. The major toxicity was leukopenia (grade I, 20%; grade II, 45%; grade III, 15%; and grade IV, 10%). Ten patients (50%) developed distant metastasis after a median follow-up time of 20 months. Our preliminary data indicate that postradiation adjuvant chemotherapy with a weekly FP regimen at our dosage is not recommended for high-risk NPC.