Treatment for pancreatic cancer may target tumor microenvironment
(21 November 2009: VIDYYA MEDICAL NEWS SERVICE) -- Researchers have found some clues to suggest why combining nab-paclitaxel (Abraxane) with gemcitabine may be a more effective treatment for advanced pancreatic cancer than gemcitabine alone, the current standard of care.
This spring, updated results from an early stage clinical trial testing the combination therapy showed a promising response, particularly in patients whose tumors produced an abundance of the protein known as SPARC. Results from a mouse model study presented today at the AACR-NCI-EORTC Molecular Targets and Cancer Therapeutics conference in Boston indicate that adding nab-paclitaxel to gemcitabine may improve response to treatment in part by altering the supportive tissue around the tumor, or stroma, allowing more gemcitabine to reach tumor cells.
The finding “shows that effective treatment does not necessarily require a fancy new molecular therapy, but just the smart combination of what is already available,” said the study’s lead investigator, Dr. Anirban Maitra from the Johns Hopkins University School of Medicine. Gemcitabine is the standard first-line treatment for pancreatic cancer, and nab-paclitaxel, a different form of paclitaxel (Taxol) that is bound to the protein albumin to improve its delivery, is approved for metastatic breast cancer.
To conduct the study, the research team tested the combination in pancreatic cancer mouse models generated at Johns Hopkins. Mice that received the combination were twice as likely to respond to the treatment as those that received gemcitabine alone, with an overall response rate (at least some tumor shrinkage) of 57 percent. They also found that mice given the combination therapy had significantly less of the “abundant fibrotic stroma” that typically surrounds pancreatic tumors and which was always seen in mice given only gemcitabine or no treatment at all. The concentration of gemcitabine in tumors from mice that received the combination therapy was 3.7-fold higher than in the animals given only gemcitabine.
Nab-paclitaxel was recently granted orphan drug status by the FDA (making it eligible for expedited FDA review and extended patent protection, among other things) for use in patients with pancreatic cancer and advanced melanoma. Enrollment is currently open for a phase III trial for pancreatic cancer that will compare gemcitabine plus nab-paclitaxel against gemcitabine alone.
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