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Clinical Trial
. 2012 Jun;30(3):1175-83.
doi: 10.1007/s10637-011-9658-9. Epub 2011 Mar 22.

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

A B El-Khoueiry  1 , R K Ramanathan, D Y Yang, W Zhang, S Shibata, J J Wright, D Gandara, H J Lenz
Affiliations
Clinical Trial

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

A B El-Khoueiry et al. Invest New Drugs. 2012 Jun.

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.

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Conflict of interest statement

Disclosures Dr. Heinz-Josef Lenz receives clinical trial funding from Bayer Phrmaceuticals. Dr. Anthony El-Khoueiry is on the speaker’s bureau for Bayer Pharmaceuticals. No other authors have conflicts of interest.

Figures

Fig. 1
Fig. 1
PFS for arm A and arm B
Fig. 2
Fig. 2
Recursive partitioning analysis: recursive partitioning (RP) was used to explore gene polymorphisms for identifying homogeneous subgroups for progression or death in the gemcitabine and sorafenib arm. In the case of PFS, compared to the most favorable group (carrying A/G of RRM1 G2464A), patients in the least favorable group (carrying A/A of RRM1 G2464A and C/C of RRM1 T524C) had HR of 7.39 (95% CI: 1.16–46.94) and PFS of 1.8 months (95%CI 1.1–2.6). In the case of OS, patients carrying genotype A/A of RRM1 G2464A, A/G or GG of RRM1 A2455G and T/C or C/C of COX-2 T8473C had the highest HR (3.79) and shortest median OS (4.4 months) compared to the most favorable group (carrying A/G of RRM1 G2464A)
See this image and copyright information in PMC

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