Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99] — Ann Oncol

Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99]
P. Albers1,*, S.-I. Park2, G. Niegisch1, G. Fechner2, U. Steiner3, J. Lehmann4, D. Heimbach5, A. Heidenreich6, R. Fimmers7, R. Siener2 and for the AUO Bladder Cancer Group

Ann Oncol (2011) 22 (2): 288-294.
doi: 10.1093/annonc/mdq398
First published online: August 2, 2010


+ Author Affiliations
1Department of Urology, Düsseldorf University, Düsseldorf
2Department of Urology, Bonn University, Bonn
3Department of Urology, Charité University Berlin, Berlin
4Department of Urology, Homburg University, Homburg
5Department of Urology, St. Vincenz Hospital, Datteln
6Department of Urology, Aachen University, Aachen
7Institute of Medical Biometry, Informatics and Epidemiology, Bonn University, Bonn, Germany


*Correspondence to: Prof. Dr P. Albers, Department of Urology, Heinrich-Heine-University,Moorenstrasse 5, 40225 Düsseldorf, Germany. Tel: +49-221-81-18-110; Fax: +49-221-81-18-676; E-mail: peter.albers@med.uni-duesseldorf.de


Received May 17, 2010.
Accepted May 31, 2010.


Abstract
Background: The second-line chemotherapeutic treatment for metastatic urothelial cancer (UC) after failure of cisplatin-based first-line therapy needs to be improved. Based on encouraging phase II data of gemcitabine and paclitaxel (Taxol) (GP), this trial was designed to compare a short-term (arm A) versus a prolonged (arm B) second-line combination chemotherapy of GP.

Patients and methods: Of 102 randomized patients, 96 were eligible for analysis. Primary end point was overall survival (OS). Secondary end points were progression-free survival (PFS), objective response rates (ORR) and toxicity.

Results: Neither OS [arm A: 7.8 (95% CI: 4.2–11.4), arm B: 8.0 (95% CI: 4.9–11.1) months] and PFS [arm A: 4.0 (95% CI: 0–8.0), arm B: 3.1 (95% CI: 1.9–4.2) months] nor ORR (arm A: 37.5%, arm B: 41.5%) were significantly different. On prolonged treatment, more patients experienced severe anemia (arm A: 6.7% versus arm B: 26.7% grade III/IV anemia; P = 0.011). In six patients, treatment was stopped during the first cycle due to disease progression or toxicity. Two patients died due to treatment-related toxic effects.

Conclusion: Due to rapid tumor progression and toxicity at this dosage and schedule in a multicenter setting, it was not feasible to deliver a prolonged regimen. However, a high response rate of ∼40% makes GP a promising second-line treatment option for patients with metastatic UC.

Randomized phase III trial of 2nd line gemcitabine and paclitaxel chemotherapy in patients with advanced bladder cancer: short-term versus prolonged treatment [German Association of Urological Oncology (AUO) trial AB 20/99] — Ann Oncol