Annals of Oncology Advance Access published online on January 30, 2009
Annals of Oncology, doi:10.1093/annonc/mdn690
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A phase II, randomized trial of neo-adjuvant chemotherapy comparing a three-drug combination of paclitaxel, ifosfamide, and cisplatin (TIP) versus paclitaxel and cisplatin (TP) followed by radical surgery in patients with locally advanced squamous cell cervical carcinoma: the Snap-02 Italian Collaborative Study
1 Department of Obstetrics and Gynecology, University of Milano-Bicocca, S. Gerardo Hospital, Monza
2 European Institute of Oncology, Milan
3 Department of Obstetrics and Gynecology, Mauriziano Hospital, Turin
4 Department of Obstetrics and Gynecology, Policlinico University of Turin, Turin
5 Department of Obstetrics and Gynecology, Treviglio Hospital, Treviglio
6 Department of Oncology, "Mario Negri" Institute, Milan, Italy
* Correspondence to: Dr R. Fossati, Istituto Mario Negri, Via Giuseppe La Masa 19, 20156 Milan, Italy. Tel: +30-02-390-14-467; Fax: +39-02-332-00-231; E-mail: fossati{at}marionegri.it
Background: The efficacy and tolerability of the regimen containing paclitaxel and cisplatin (TP) in the neo-adjuvant treatment of locally advanced squamous cell cervical cancer are unknown. The TIP regimen (TP plus ifosfamide) showed high efficacy but high toxicity and it is used as an internal control.
Patients and methods: In all, 154 patients were randomized to TP (paclitaxel 175 mg/m2 + cisplatin 75 mg/m2; n = 80) or TIP (TP + ifosfamide 5 g/m2; n = 74), three cycles, followed by radical surgery. Pathological response to chemotherapy was classified as optimal [no residual tumor (complete response) or residual disease with 
3 mm stromal invasion (PR1)] or suboptimal response.
Results: Patient characteristics (TP/TIP): stage IB2 (56%/64%), IIA (18%/14%), IIB (20%/19%), III–IVA (5%/4%) and median age (42 years/45 years). The optimal response rate in the TP group was 25%, 95% confidence interval (CI) = 16% to 37% and 43%, 95% CI = 31% to 55% in the TIP group. Grades 3–4 leukopenia (6%/53%) and neutropenia (26%/76%) were significantly more frequent on TIP.
Conclusion: TP performance was below expectation since the lower 95% confidence limit of the optimal response rate failed to reach the prespecified minimum requirement of efficacy, i.e. 22%. The TIP regimen confirmed its activity but was associated with higher haematological toxicity than TP.
cisplatin, ifosfamide, locally advanced cervical carcinoma, neo-adjuvant chemotherapy, paclitaxel, randomized trial
Received for publication July 19, 2008. Revision received September 16, 2008. Accepted for publication October 1, 2008.