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.
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.


METHODS
In all, 154 patients were randomized to TP (paclitaxel 175 mg/m(2) + cisplatin 75 mg/m(2); n = 80) or TIP (TP + ifosfamide 5 g/m(2); 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 < or = 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.


CONCLUSIONS
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.
Lissoni
A A
AA
Department of Obstetrics and Gynecology, University of Milano-Bicocca, S Gerardo Hospital, Monza, Italy.
Colombo
N
N
Pellegrino
A
A
Parma
G
G
Zola
P
P
Katsaros
D
D
Chiari
S
S
Buda
A
A
Landoni
F
F
Peiretti
M
M
Dell'anna
T
T
Fruscio
R
R
Signorelli
M
M
Grassi
R
R
Floriani
I
I
Fossati
R
R
Torri
V
V
Rulli
E
E
D000328:Adult; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000601:surgery*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D003131:Combined Modality Therapy; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000009:adverse effects; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage* / Q000009:adverse effects; D043823:Taxoids / Q000008:administration & dosage / Q000009:adverse effects; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000601:surgery*
D043823:Taxoids; D017239:Paclitaxel; D002945:Cisplatin; D007069:Ifosfamide