title: Concurrent 5-fluorouracil, mitomycin C and radiation with or without brachytherapy in recurrent cervical cancer: a scoring system to predict clinical response and outcome.
abstract: OBJECTIVE
  This is a prospective, phase II study aimed to evaluate the effect of concurrent 5-fluorouracil, mitomycin C, and radiation with or without brachytherapy on the clinical outcome of a series of recurrent cervical cancer patients and to determine the prognostic impact of a subset of factors.
  
  
  METHODS
  Thirty-three patients with locally recurrent, non-metastatic cervical cancer received external beam radiation (4-week split course: 23.4 + 23.4 Gy) plus two courses of concomitant chemotherapy (5-fluorouracil, 96-h continuous infusion, days 1-4, 1 g/m2/day; mitomycin C, 10 mg/m2, bolus i.v., day 1). Twelve patients with vaginal recurrence (36.4%) underwent endocavitary low-dose rate brachytherapy boost (20-25 Gy); 11 patients with lateral pelvic recurrence (33.3%) received external beam radiation boost (14-20 Gy).
  
  
  RESULTS
  Fourteen complete responses (42.4%), 7 partial responses (21.2%), 5 disease stabilizations (15.1%) and 7 progressions (21.2%) were obtained. After a median follow-up of 34 months (range, 6-127), overall actuarial 3-year survival, progression-free survival and local progression-free survival were 59.7%, 48.1% and 51.7%, respectively. Patients with vaginal recurrence of less than 4 cm and negative lymph nodes proved to respond best to the treatment. Two patients (6.1%) experienced hematologic grade 3 toxicity. One patient had grade 3 intestinal toxicity (3.0%). No patient had major skin or urological acute toxicity. Severe late toxicity was infrequent. Three patients had prolonged leukopenia (9.0%). Four patients showed severe vaginal stenosis (12.1%). A clinical score of 0 to 1 was assigned to each patient on the basis of the absence (score = 0) or presence (score = 1) of any of the following prognostic factors: time between surgery and recurrence shorter than 12 months, pelvic wall site of recurrence, positive lymph nodes, hemoglobin < 11 g/dL. Using this system, it was clear that patients with a low total score had a significantly better outcome (clinical remission, 51% of patients with a score < or = 2 vs 12% of patients with a score > 2, P = 0.06), local control of the disease (65% vs 20% after 3 years, P = 0.001,) and overall survival (75% vs 30% after 3 years, P = 0.032).
  
  
  CONCLUSIONS
  Our data suggest that this combined modality therapy was relatively well tolerated and resulted in reasonable local control and survival. The scoring system proved to be helpful to identify patients with the greatest chance of benefiting from the treatment. Further studies are probably needed to salvage the other patients, whose prognosis remains severe.
authors.affiliation: Department of Radiation Oncology, Catholic University of the Sacred Heart, Rome, Italy. dsmaniotto@rm.unicatt.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Smaniotto
authors.forename: Giuseppe
authors.initials: G
authors.lastname: D'Agostino
authors.forename: Stefano
authors.initials: S
authors.lastname: Luzi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Valentini
authors.forename: Gabriella
authors.initials: G
authors.lastname: Macchia
authors.forename: Giovanna
authors.initials: G
authors.lastname: Mantini
authors.forename: Pasquale Alessandro
authors.initials: PA
authors.lastname: Margariti
authors.forename: Gabriella
authors.initials: G
authors.lastname: Ferrandina
authors.forename: Giovanni
authors.initials: G
authors.lastname: Scambia
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001918:Brachytherapy; D017024:Chemotherapy, Adjuvant; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000532:radiotherapy*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D018714:Radiotherapy, Adjuvant; D016019:Survival Analysis; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*
chemical_list: D000970:Antineoplastic Agents; D016685:Mitomycin; D005472:Fluorouracil