Correlation of clinical outcome with p53 and p21 status in patients with advanced transitional-cell carcinoma treated with paclitaxel and carboplatin.
BACKGROUND
The purpose of the present study was to correlate the nuclear expression of p53 and p21 with response to paclitaxel and carboplatin, progression-free survival (PFS) as well as overall survival (OS), in patients with urothelial metastatic transitional-cell carcinoma (TCC).


METHODS
Histological specimens of 23 patients with metastatic TCC, who were treated with paclitaxel and carboplatin, were investigated for p53 and p21 proteins and correlated with overall response (OR) to chemotherapy, PFS and OS.


RESULTS
After a median follow-up of 33.2 months, the OR rate was 57%. Median PFS was 7.4 (range: 2.5-49.2) months while median OS was 13.2 (range: 4.2-49.5) months. The tumour specimens of 48% of patients were classified as p53-positive, whereas 57% were classified as p21-positive. Neither p53- nor p21-status were significantly associated with CR, CR and PR or CR, PR and SD. In addition, neither PFS nor OS were significantly influenced by p53- and p21-status.


CONCLUSIONS
Previous findings on the efficacy of the combination of paclitaxel and carboplatin in metastatic TCC patients are thus re-confirmed even after a considerable duration of follow-up. Moroever, the clinically relevant results obtained were independent from p53- or p21-status thus suggesting the involvement of other, yet unidentified, pathways as prognostic indicators for the course of the disease under the present treatment.
Flamm
Maria
M
Department of Urology, University Hospital, Vienna, Austria.
Brodowicz
Thomas
T
Haitel
Andrea
A
Susani
Martin
M
Tomek
Sandra
S
Köstler
Wofgang
W
Pycha
Armin
A
Kratzik
Christian
C
Marberger
Michael
M
Zielinski
Christoph C
CC
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000556:secondary; D002467:Cell Nucleus / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000096:biosynthesis*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017239:Paclitaxel / Q000008:administration & dosage; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53; D016190:Carboplatin; D017239:Paclitaxel