A phase II safety and efficacy study of the vascular endothelial growth factor receptor tyrosine kinase inhibitor pazopanib in patients with metastatic urothelial cancer.

Abstract

BACKGROUND:

Vascular endothelial growth factor (VEGF) is produced by bladder cancer cell lines in vitro and expressed in human bladder tumor tissues. Pazopanib is a vascular endothelial receptor tyrosine kinase inhibitor with anti-angiogenesis and anti-tumor activity in several preclinical models. A 2-stage phase II study was conducted to assess the activity and toxicity profile of pazopanib in patients with metastatic, urothelial carcinoma.

METHODS:

Patients with one prior systemic therapy for metastatic urothelial carcinoma were eligible. Patients received pazopanib at a dose of 800 mg orally for a 4-week cycle.

RESULTS:

Nineteen patients were enrolled. No grade 4 or 5 events were experienced. Nine patients experienced 11 grade 3 adverse events. Most common toxicities were anemia, thrombocytopenia, leucopenia, and fatigue. For stage I, none of the first 16 evaluable patients were deemed a success (complete response or partial response) by the Response Evaluation Criteria In Solid Tumors criteria during the first four 4-week cycles of treatment. Median progression-free survival was 1.9 months. This met the futility stopping rule of interim analysis, and therefore the trial was recommended to be permanently closed.

CONCLUSIONS:

Pazopanib did not show significant activity in patients with urothelial carcinoma. The role of anti-VEGF therapies in urothelial carcinoma may need further evaluation in rational combination strategies.

• Authors: Roberto Pili, Rui Qin, P J Flynn, Joel Picus, Michael Millward, Wing Ming Ho, Henry Pitot, Winston Tan, Kiersten M Miles, Charles Erlichman, Ulka Vaishampayan
• Journal: Clinical genitourinary cancer (Clin Genitourin Cancer) Vol. 11 Issue 4 Pg. 477-83 (Dec 2013) ISSN: 1938-0682 [Electronic] United States
• PMID: 23891158 (Publication Type: Clinical Trial, Phase II, Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Angiogenesis Inhibitors
• Indazoles
• Pyrimidines
• Sulfonamides
• pazopanib
• Receptors, Vascular Endothelial Growth Factor

Topics

• Adult
• Aged
• Aged, 80 and over
• Angiogenesis Inhibitors (adverse effects, therapeutic use)
• Carcinoma, Transitional Cell (drug therapy, mortality)
• Disease-Free Survival
• Female
• Humans
• Indazoles
• Male
• Middle Aged
• Neovascularization, Pathologic (drug therapy)
• Pyrimidines (adverse effects, therapeutic use)
• Receptors, Vascular Endothelial Growth Factor (antagonists & inhibitors)
• Sulfonamides (adverse effects, therapeutic use)
• Treatment Failure
• Urologic Neoplasms (drug therapy, mortality)
• Urothelium (drug effects, pathology)