Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type

Background: This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisp latin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic u ndifferentiated carcinoma of nasopharyngeal type (UCNT). Patients and methods: Between July 1989 and December 1991, 44 consecutive p atients (M/F 36/8; median age: 45, range 20-72; performance status (PS) 0: 20 patients, PS 1: 14 patients, PS 2: 10 patients) with recurrent or metast atic UCNT were entered in this study after complete clinical, biological, a nd radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consi sted of 800 mg/m(2)/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m(2) epirubicin, 10 mg/m(2) mitomycin, and 100 m g/m(2) cisplatin on day 1, every four weeks for six cycles. Mitomycin was d elivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regi onal recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response wer e evaluated according to WHO criteria. Toxicity: Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 pati ents (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed i n 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) wi th mitomycin. Grade 3 anemia was noted in 18 patients (40%) and 23 cycles ( 11%), including 18 of 23 cycles (78%) with mitomycin. Grade 3-4 mucositis o ccurred in 25 cycles (11%) and 14 patients (32%), mainly in those previousl y treated with radiation therapy in the head and neck area. There were four treatment-related deaths (9%); three of them neutropenia-related, and one of cardiac toxicity. Response: Forty-four patients were evaluable for response: There were 23 of 44 objective responses (52%), including six complete responses (13%), and 17 partial responses (38%). Additional radiotherapy was given to 13 patient s after documentation of response: Nasopharyngeal tumor + cervical nodes (e ight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-10 0), five patients are alive and in continuous complete remission. The media n survival time was 14 months and the median time to progression nine month s. Conclusion: The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.