A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer

A. B. El-Khoueiry, R. K. Ramanathan, D. Y. Yang, W. Zhang, S. Shibata, J. J. Wright, David R Gandara, H. J. Lenz

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Purpose Patients with metastatic pancreatic cancer have limited therapeutic options. The role of the Ras-Raf-MAPK pathway and of vascular endothelial growth factor in pancreatic carcinogenesis provided the rational to evaluate the efficacy of sorafenib with or without gemcitabine in a randomized phase II study. Methods Patients with metastatic pancreatic cancer were randomized to sorafenib alone (arm A) or sorafenib with gemcitabine (arm B). Results Arm A was closed to accrual at interim analysis due to the lack of objective response. Median PFS and OS were 2.3 and 4.3 months respectively. There was one partial response among the 37 patients in arm B. Median PFS and OS were 2.9 and 6.5 months respectively. There were more grade 3 and 4 toxicities in arm B with the most common being neutropenia (17%), thrombocytopenia (8%), alkaline phosphatase elevation (14%), venous thromboembolism (8%), diarrhea, hypokalemia and ALT elevation (5%) each. Several associations were noted between single nucleotide polymorphisms in ribonucleotide reductase, Cox-2, vascular endothelial growth factor and survival in patients treated with gemcitabine and sorafenib. Conclusions Neither sorafenib alone or sorafenib in combination with gemcitabine manifested promising activity in metastatic pancreatic cancer.

Original languageEnglish (US)
Pages (from-to)1175-1183
Number of pages9
JournalInvestigational New Drugs
Volume30
Issue number3
DOIs
StatePublished - Jun 2012

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gemcitabine
Pancreatic Neoplasms
Vascular Endothelial Growth Factor A
Ribonucleotide Reductases
Hypokalemia
Venous Thromboembolism
Neutropenia
Thrombocytopenia
Single Nucleotide Polymorphism
Alkaline Phosphatase
sorafenib
Diarrhea
Carcinogenesis

Keywords

  • Gemcitabine
  • Pancreatic cancer
  • Ribonulceotide reductase
  • Sorafenib

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Oncology

Cite this

El-Khoueiry, A. B., Ramanathan, R. K., Yang, D. Y., Zhang, W., Shibata, S., Wright, J. J., ... Lenz, H. J. (2012). A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer. Investigational New Drugs, 30(3), 1175-1183. https://doi.org/10.1007/s10637-011-9658-9

A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer. / El-Khoueiry, A. B.; Ramanathan, R. K.; Yang, D. Y.; Zhang, W.; Shibata, S.; Wright, J. J.; Gandara, David R; Lenz, H. J.

In: Investigational New Drugs, Vol. 30, No. 3, 06.2012, p. 1175-1183.

Research output: Contribution to journalArticle

El-Khoueiry, A. B. ; Ramanathan, R. K. ; Yang, D. Y. ; Zhang, W. ; Shibata, S. ; Wright, J. J. ; Gandara, David R ; Lenz, H. J. / A randomized phase II of gemcitabine and sorafenib versus sorafenib alone in patients with metastatic pancreatic cancer. In: Investigational New Drugs. 2012 ; Vol. 30, No. 3. pp. 1175-1183.
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