title: Randomized trial of neoadjuvant chemotherapy comparing paclitaxel, ifosfamide, and cisplatin with ifosfamide and cisplatin followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the SNAP01 (Studio Neo-Adjuvante Portio) Italian Collaborative Study.
abstract: OBJECTIVE
  Neoadjuvant chemotherapy may represent an alternative to irradiation in locally advanced squamous cell cervical cancer. Aims of this study were to compare a three-drug (paclitaxel, ifosfamide, and cisplatin [TIP]) with a two-drug (ifosfamide and cisplatin [IP]) regimen and to assess the prognostic value of pathologic response on survival.
  
  
  METHODS
  Patients (n = 219) were randomly assigned to ifosfamide 5 g/m(2) during 24 hours plus cisplatin 75 mg/m(2), or paclitaxel 175 mg/m(2) plus ifosfamide 5 g/m(2) during 24 hours and cisplatin 75 mg/m(2) every 3 weeks for three courses.
  
  
  RESULTS
  Grades 3 to 4 neutropenia, anemia, and thrombocytopenia were more frequent with TIP. We recorded four deaths related to toxicity. The optimal pathologic response (OPT) rate (residual disease < 3 mm stromal invasion) was higher with TIP than with IP (48% v 23%; odds ratio, 3.22; 95% CI, 1.69 to 5.88; P = .0003). At a median follow-up of 43.4 months, 79 women experienced disease progression or died (46 in the IP arm, 33 in the TIP arm). Patients receiving TIP experienced a treatment failure rate 25% less than those receiving IP, but this difference was not statistically significant (hazard ratio [HR], 0.75; 95% CI, 0.48 to 1.17; P = .20). Sixty-one patients died (37 in the IP arm, 24 in the TIP arm), and the HR of death was in favor of TIP, although not significantly (HR, 0.66; 95% CI, 0.39 to 1.10; P = .11). In patients assessable for response (n = 189), the average death rates were higher in the group that did not achieve OPT (HR, 5.88; 95% CI, 2.50 to 13.84; P < .0001).
  
  
  CONCLUSIONS
  The TIP regimen is associated with a higher response rate than the IP regimen, without a statistically significant effect on overall survival. OPT was a prognostic factor for survival.
authors.affiliation: Department of Obstetrics and Gynecology, University of Milano-Bicicca, San Gerardo Hospital, Monza, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Buda
authors.forename: Roldano
authors.initials: R
authors.lastname: Fossati
authors.forename: Nicoletta
authors.initials: N
authors.lastname: Colombo
authors.forename: Francesca
authors.initials: F
authors.lastname: Fei
authors.forename: Irene
authors.initials: I
authors.lastname: Floriani
authors.forename: Desiderio
authors.initials: D
authors.lastname: Gueli Alletti
authors.forename: Dionyssios
authors.initials: D
authors.lastname: Katsaros
authors.forename: Fabio
authors.initials: F
authors.lastname: Landoni
authors.forename: Andrea
authors.initials: A
authors.lastname: Lissoni
authors.forename: Carmine
authors.initials: C
authors.lastname: Malzoni
authors.forename: Enrico
authors.initials: E
authors.lastname: Sartori
authors.forename: Paolo
authors.initials: P
authors.lastname: Scollo
authors.forename: Valter
authors.initials: V
authors.lastname: Torri
authors.forename: Paolo
authors.initials: P
authors.lastname: Zola
authors.forename: Costantino
authors.initials: C
authors.lastname: Mangioni
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy*; D016009:Chi-Square Distribution; D002945:Cisplatin / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000627:therapeutic use*; D007558:Italy; D016015:Logistic Models; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D016016:Proportional Hazards Models; D016019:Survival Analysis; D043823:Taxoids / Q000627:therapeutic use*; D016896:Treatment Outcome; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy*
chemical_list: D043823:Taxoids; D002945:Cisplatin; D007069:Ifosfamide