Larotaxel with Cisplatin in the first-line treatment of locally advanced/metastatic urothelial tract or bladder cancer: a randomized, active-controlled, phase III trial (CILAB).

Abstract

BACKGROUND:

This open-label, randomized phase III trial evaluated larotaxel/cisplatin versus gemcitabine/cisplatin as first-line treatment for locally advanced (T4b) or metastatic urothelial tract or bladder cancer.

METHODS:

Patients were randomized to larotaxel 50 mg/m(2) with cisplatin 75 mg/m(2) every 3 weeks (larotaxel/cisplatin) or gemcitabine 1,000 mg/m(2) on days 1, 8, and 15 with cisplatin 70 mg/m(2) on day 1 every 4 weeks (gemcitabine/cisplatin). The primary endpoint was overall survival (OS).

RESULTS:

The trial was prematurely closed following the sponsor's decision to stop clinical development of larotaxel (n = 337 randomized). The larotaxel dose was reduced to 40 mg/m(2) and cisplatin to 60 mg/m(2) following a data monitoring committee safety review of the first 97 patients. At the time of analysis, the median OS was 13.7 months [95% confidence interval (CI) 11.2-17.1] with larotaxel/cisplatin and 14.3 months (95% CI 10.5 to not reached) with gemcitabine/cisplatin [hazard ratio (HR) 1.21; 95% CI 0.83-1.76; p = 0.33]. The median progression-free survival (PFS) was 5.6 months (95% CI 4.1-6.2) with larotaxel/cisplatin and 7.6 months (95% CI 6.6-9.1) with gemcitabine/cisplatin (HR 1.67; 95% CI 1.24-2.25). More myelosuppression was observed with gemcitabine/cisplatin.

CONCLUSION:

There was no difference in OS. Although the trial was closed prematurely, PFS appeared worse with larotaxel/cisplatin, suggesting that larotaxel/cisplatin does not improve outcomes versus cisplatin/gemcitabine.

• Authors: Cora N Sternberg, Iwona A Skoneczna, Daniel Castellano, Christine Theodore, Normand Blais, Eric Voog, Joaquim Bellmunt, Frank Peters, Solenn Le-Guennec, Linda Cerbone, Marie-Laure Risse, Jean-Pascal Machiels
• Journal: Oncology (Oncology) Vol. 85 Issue 4 Pg. 208-15 ( 2013) ISSN: 1423-0232 [Electronic] Switzerland
• PMID: 24080920 (Publication Type: Clinical Trial, Phase III, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2013 S. Karger AG, Basel.

Chemical References

• Antineoplastic Agents
• Taxoids
• Deoxycytidine
• Cisplatin
• larotaxel
• Gemcitabine

Topics

• Adult
• Aged
• Aged, 80 and over
• Antineoplastic Agents (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Carcinoma, Transitional Cell (drug therapy, mortality, pathology)
• Cisplatin (administration & dosage)
• Deoxycytidine (administration & dosage, analogs & derivatives)
• Disease-Free Survival
• Female
• Humans
• Male
• Middle Aged
• Neoplasm Recurrence, Local (drug therapy)
• Prospective Studies
• Survival Analysis
• Taxoids (administration & dosage)
• Treatment Outcome
• Urinary Bladder Neoplasms (drug therapy, mortality, pathology)
• Urothelium (pathology)
• Gemcitabine