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.
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.
Buda
Alessandro
A
Department of Obstetrics and Gynecology, University of Milano-Bicicca, San Gerardo Hospital, Monza, Italy.
Fossati
Roldano
R
Colombo
Nicoletta
N
Fei
Francesca
F
Floriani
Irene
I
Gueli Alletti
Desiderio
D
Katsaros
Dionyssios
D
Landoni
Fabio
F
Lissoni
Andrea
A
Malzoni
Carmine
C
Sartori
Enrico
E
Scollo
Paolo
P
Torri
Valter
V
Zola
Paolo
P
Mangioni
Costantino
C
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*
D043823:Taxoids; D002945:Cisplatin; D007069:Ifosfamide