Researchers from Germany have reported that the addition of Eloxatin (oxaliplatin) or Platinol (cisplatin) to Gemzar (gemcitabine) improves progression-free (PFS) and overall survival (OS) in patients with advanced pancreatic cancer. [1] The results of this meta-analysis of two randomized German trials were presented at the 2006 annual meeting of the American Society of Clinical Oncology. A second report at the same meeting suggested that Avastin® (bevacizumab) could be added to a regimen of Gemzar and Eloxatin without increasing toxicity in patients with advanced pancreatic cancer.[2]

Gemzar is standard therapy for patients with pancreatic cancer. There is evolving evidence that the addition of a platinum compound to Gemzar can improve responses and possibly overall outcomes of patients with advanced pancreatic cancer. Eloxatin is being increasingly evaluated in platinum-sensitive cancers as it is possible less toxic than Platinol or Paraplatin® (carboplatin). 

These authors looked at two randomized studies evaluating the impact of adding Eloxatin or Platinol to Gemzar for the treatment of advanced pancreatic cancer. In each study there were trends for improved outcome in patients treated with two drugs versus those treated with Gemzar alone. The two studies together had over 500 patients and when combined there was more power for statistical observations. They reported that the median PFS was 5.5 months for two drug therapy and 3.6 months for single drug therapy. The effect was greatest in patients with excellent performance status. The median OS for patients with ECOG 0 performance status was 8.3 months for combination therapy and 6.7 months for single agent therapy. These authors concluded that the addition of a platinum compound significantly improved PFS and OS of patients with advanced pancreatic cancer.

At ASCO 2006, Researchers affiliated with the North Central Cancer Treatment Group (NCCTG) reported that the addition of Avastin to Gemzar and Eloxatin was well tolerated.

Avastin is a recombinant humanized monoclonal antibody to vascular endothelial growth factor (VEGF). VEGF appears to play an important role in tumor angiogenesis, and blocking this activity should have an anti-tumor effect.

Clinical trials of Avastin have shown activity in a variety of tumors, especially when combined with other agents. However, there have been no reports of Avastin as a single agent for the treatment of pancreatic cancer. However, there is suggestive evidence that the addition of Tarceva® (erlotinib) may improve the outcomes of patients with advanced pancreatic cancer treated with Gemzar (see related news). Tarceva has been approved by the FDA for the treatment of patients with recurrent NSCLC, and Avastin is approved for the treatment of advanced colorectal cancer. Tarceva is an epidermal growth factor receptor tyrosine kinase inhibitor, and Avastin targets the vascular endothelial growth factor pathway.

This late breaking abstract suggested that Avastin could be added safely to a regimen of Gemzar and Eloxatin without increasing toxicity. It will be of major interest to see if this approach improves PFS and OS.

Comments:  These and other studies suggest that a regimen of Gemzar and Eloxatin with a targeted biological agent such as Avastin or Tarceva may improve outcomes of patients with pancreatic cancer.

Related News

Gemzar® Plus Oxaliplatin is a Well Tolerated Palliative Combination for Patients with Advanced Pancreatic Cancer  (4/22/2002)

Addition of Tarceva™ to Gemzar® Improves Survival in Pancreatic Cancer  (5/15/2005)

Gemzar® - New Standard of Care in Adjuvant Therapy for Pancreatic Cancer  (5/15/2005)

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