Randomized Phase III Study Comparing Paclitaxel/Cisplatin/ Gemcitabine and Gemcitabine/Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Cancer Without Prior Systemic Therapy: EORTC Intergroup Study 30987
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- 1 April 2012
- journal article
- research article
- Published by American Society of Clinical Oncology (ASCO) in Journal of Clinical Oncology
- Vol. 30 (10), 1107-1113
- https://doi.org/10.1200/jco.2011.38.6979
Abstract
The combination of gemcitabine plus cisplatin (GC) is a standard regimen in patients with locally advanced or metastatic urothelial cancer. A phase I/II study suggested that a three-drug regimen that included paclitaxel had greater antitumor activity and might improve survival. We conducted a randomized phase III study to compare paclitaxel/cisplatin/gemcitabine (PCG) with GC in patients with locally advanced or metastatic urothelial carcinoma. Primary outcome was overall survival (OS). Secondary outcomes were progression-free survival (PFS), overall response rate, and toxicity. From 2001 to 2004, 626 patients were randomly assigned; 312 patients were assigned to PCG, and 314 patients were assigned to GC. After a median follow-up of 4.6 years, the median OS was 15.8 months on PCG versus 12.7 months on GC (hazard ratio [HR], 0.85; P = .075). OS in the subgroup of all eligible patients was significantly longer on PCG (3.2 months; HR, 0.82; P = .03), as was the case in patients with bladder primary tumors. PFS was not significantly longer on PCG (HR, 0.87; P = .11). Overall response rate was 55.5% on PCG and 43.6% on GC (P = .0031). Both treatments were well tolerated, with more thrombocytopenia and bleeding on GC than PCG (11.4% v 6.8%, respectively; P = .05) and more febrile neutropenia on PCG than GC (13.2% v 4.3%, respectively; P < .001). The addition of paclitaxel to GC provides a higher response rate and a 3.1-month survival benefit that did not reach statistical significance. Novel approaches will be required to obtain major improvements in survival of incurable urothelial cancer.Keywords
This publication has 27 references indexed in Scilit:
- Prognostic Significance of Bladder Tumor History and Tumor Location in Upper Tract Transitional Cell CarcinomaJournal of Urology, 2006
- RECIST revisited: A review of validation studies on tumour assessmentEuropean Journal of Cancer, 2006
- Promoter Hypermethylation Is Associated With Tumor Location, Stage, and Subsequent Progression in Transitional Cell CarcinomaJournal of Clinical Oncology, 2005
- Urothelial umbrella cells of human ureter are heterogeneous with respect to their uroplakin composition: different degrees of urothelial maturity in ureter and bladder?European Journal of Cell Biology, 2005
- Spreading of embryologically distinct urothelial cells is inhibited by SPARCJournal of Cellular Physiology, 2004
- Distinct patterns of microsatellite instability are seen in tumours of the urinary tractOncogene, 2003
- Frequent microsatellite instability in sporadic tumors of the upper urinary tract.2002
- Pretreatment prognostic factors for survival in patients with advanced urothelial tumors treated in a phase I/II trial with paclitaxel, cisplatin, and gemcitabineCancer, 2002
- New Guidelines to Evaluate the Response to Treatment in Solid TumorsJNCI Journal of the National Cancer Institute, 2000
- A phase II study of gemcitabine in patients with transitional cell carcinoma of the urinary tract previously treated with platinumEuropean Journal of Cancer, 1998