Induction chemotherapy with mitomycin, epirubicin, cisplatin, fluorouracil, and leucovorin followed by radiotherapy in the treatment of locoregionally advanced nasopharyngeal carcinoma

Purpose : Survival in advanced nasopharyngeal carcinoma (NPC) is compromise d by distant metastasis. Because mitomycin is active against hypoxic and GO cells, which may help to eradicate micrometastasis, we investigated the ef fect of mitomycin-containing cisplatin-based induction chemotherapy. Patients and Methods: Recruited for this study were American Joint Committe e on Cancer (AJCC) 1992 staging system stage IV NPC patients with the follo wing adverse features: obvious intracranial invasion, supraclavicular or bi lateral neck lymph node metastasis, large neck node (> 6 cm), or elevated s erum lactate dehydrogenase (LDH) level. Patients were given three cycles of chemotherapy before radiotherapy. The chemotherapy comprised a 3-week cycl e of mitomycin, epirubicin, and cisplatin on day 1 and fluorouracil and leu covorin on day 8 (MEPFL). Results: From January 1994 to December 1997, 111 patients were recruited. T he median follow-up period was 43 months. The actuarial 5-year overall surv ival rate was 70% (95% confidence interval [CI], 60% to 80%; n = 111). For patients having completed radiotherapy (n = 100), the 5-year locoregional c ontrol rate was 70% (95% CI, 55% to 84%) and the distant metastasis-free ra te was 81% (95% CI, 73% to 89%). The 5-year distant metastasis-free rate of N3a and N3b disease of AJCC 1997 staging system were 79% (95% CI, 62% to 9 5%) and 74% (95% Cl, 60% to 89%), respectively. By Cox multivariate analysi s, high pretreatment serum LDH level (P =.04) and neck nodal enlargement be fore radiotherapy (P =.001) were adverse prognostic factors of survival. Conclusion: The good 5-year survival of N3 disease supports the effectivene ss of induction MEPFL in the primary treatment of advanced NPC. Further inv estigation to incorporate concurrent chemoradiotherapy is warranted. J Clin Oncol 19:4305-4313. (C) 2001 by American Society of Clinical Oncology.