title: Phase II trial combining mitomycin with 5-fluorouracil, epirubicin, and cisplatin in recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type.
abstract: BACKGROUND
  This phase-II study was conducted to investigate the potential benefit from the addition of mitomycin to a conventional anthracycline-cisplatin- and 5-fluorouracil-based chemotherapy for recurrent and metastatic undifferentiated carcinoma of nasopharyngeal type (UCNT).
  
  
  METHODS
  Between July 1989 and December 1991, 44 consecutive patients (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 metastatic UCNT were entered in this study after complete clinical, biological, and radiological pre-therapeutic work-ups. Chemotherapy (FMEP regimen) consisted of 800 mg/m2/day 5-fluorouracil in continuous infusion from day 1 to day 4 combined with 70 mg/m2 epirubicin, 10 mg/m2 mitomycin, and 100 mg/m2 cisplatin on day 1, every four weeks for six cycles. Mitomycin was delivered in cycles 1, 3, and 5 only. Eleven patients had isolated loco-regional recurrences, 12 patients had local recurrences associated with distant metastasis, and 21 patients had metastasis only. Toxicity and response were evaluated according to WHO criteria.
  
  
  RESULTS
  Grade 3-4 neutropenia was observed in 122 of 212 evaluable cycles (57%) and 39 of 44 patients (89%); febrile neutropenia occurred in 16 patients (36%) and 24 cycles (11.3%). Grade 3-4 thrombocytopenia was observed in 27 patients (61%) and 45 cycles (21%), including 27 of 45 cycles (60%) with 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 occurred in 25 cycles (11%) and 14 patients (32%), mainly in those previously 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.
  
  
  RESULTS
  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 patients after documentation of response: Nasopharyngeal tumor + cervical nodes (eight patients) and/or on bone metastasis sites (five patients); mediastinal lymph nodes (one patient). At a median follow-up of 87 months (range 71-100), five patients are alive and in continuous complete remission. The median survival time was 14 months and the median time to progression nine months.
  
  
  CONCLUSIONS
  The regimen under study is active in recurrent/metastatic UCNT, but associated with excessive toxicity.
authors.affiliation: Department of Medicine, Institut Gustave Roussy, Villejuif, France.
authors.forename: A
authors.initials: A
authors.lastname: Hasbini
authors.forename: R
authors.initials: R
authors.lastname: Mahjoubi
authors.forename: A
authors.initials: A
authors.lastname: Fandi
authors.forename: N
authors.initials: N
authors.lastname: Chouaki
authors.forename: A
authors.initials: A
authors.lastname: Taamma
authors.forename: P
authors.initials: P
authors.lastname: Lianes
authors.forename: H
authors.initials: H
authors.lastname: Cortès-Funes
authors.forename: S
authors.initials: S
authors.lastname: Alonso
authors.forename: J P
authors.initials: JP
authors.lastname: Armand
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
authors.forename: E
authors.initials: E
authors.lastname: Raymond
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002277:Carcinoma / Q000188:drug therapy* / Q000532:radiotherapy / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D015251:Epirubicin / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006402:Hematologic Diseases / Q000139:chemically induced; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D008937:Mitomycins / Q000008:administration & dosage; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000473:pathology; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate
chemical_list: D008937:Mitomycins; D015251:Epirubicin; D002945:Cisplatin; D005472:Fluorouracil