title: Neoadjuvant and adjuvant chemotherapy of cervical cancer: mature results of the phase 2 PBM-PFU protocol.
abstract: OBJECTIVE
  The mature results of the neoadjuvant and adjuvant chemotherapy arms of the nonrandomized, phase 2 Yale University cisplatin, bleomycin, methotrexate, and 5-FU protocol are presented.
  
  
  METHODS
  Sixty-seven patients were prospectively accrued with a median follow-up of 5.4 years, and standard parameters of toxicity and efficacy were studied. Both univariate and multivariate analyses were applied.
  
  
  RESULTS
  The 5-year disease-free survival of 78% for the 25 patients in the adjuvant group, of which 80% had high-risk features including positive margins, parametria, and lymph nodes and 28% had adenocarcinomas, was comparable to recent relevant literature. Only 64% of patients in this group received consolidation radiation therapy, which did not impact on survival. Only 12% of patients recurred distantly. Notably, those who received 4 months or more of chemotherapy had prolonged survival (P = 0.012). In the neoadjuvant group, chemotherapy response rate among 42 patients (with stages 1B-IIIB cancer) was 79% (50% partial response, 29% complete response), and no patient progressed. In the subgroup of 22 patients who underwent surgery after chemotherapy, 59% had nonsquamous histology. Forty-five percent of patients with stage IIB cancer were deemed operable after chemotherapy. Ninety-five percent received postoperative radiation therapy. There was a 9% pathologic complete response rate, with positive lymph nodes found in 27%. Notably, those who received 3 months or less of chemotherapy had improved overall survival (P = 0.030). Survival rates of these 22 patients at 3 and 5 years were 73% and 63%, respectively. Although not randomized, these survival rates were similar to those achieved with chemoradiation.
  
  
  CONCLUSIONS
  Although there are several logistical/design features of the cisplatin, bleomycin, methotrexate, and 5-FU regimen that are not in line with the current chemotherapy era, our experience with this well-tolerated regimen can serve as a proof of principle. Our data suggests that both neoadjuvant and adjuvant cisplatin-based neoadjuvant chemotherapy may have their place. It also raises the possibility that the optimal duration of chemotherapy in adjuvant cases should be longer than in neoadjuvant cases.
authors: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, University of Arizona, Tucson, AZ 85724, USA.
authors: Rebecca
authors: R
authors: McCaffrey
authors: Mert
authors: M
authors: Bahtiyar
authors: Ernest I
authors: EI
authors: Kohorn
authors: Joseph T
authors: JT
authors: Chambers
authors: Peter E
authors: PE
authors: Schwartz
authors: Setsuko K
authors: SK
authors: Chambers
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy*; D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001761:Bleomycin / Q000627:therapeutic use; D018196:Carcinoma, Adenosquamous / Q000188:drug therapy*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000627:therapeutic use; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000627:therapeutic use; D020714:Maximum Tolerated Dose; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D009367:Neoplasm Staging; D011446:Prospective Studies; D015996:Survival Rate; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D001761:Bleomycin; D002945:Cisplatin; D002955:Leucovorin; D005472:Fluorouracil; D008727:Methotrexate