Combination Therapy May Enhance Gemcitabine Activity for Pancreatic Cancer
- Nab-paclitaxel appears to enhance gemcitabine activity.
- Study also shows the potential value of a time-delay administration.
- Combination treatment regimen already in late-stage phase III clinical trial.
PHILADELPHIA — Oncologists who treat patients with pancreatic cancer may be one step closer to understanding why gemcitabine, the only currently available treatment, works in some cases but not in others, according to a paper in Cancer Discovery, a journal of the American Association for Cancer Research.
David Tuveson, M.D., Ph.D., a professor of pancreatic cancer medicine at the University of Cambridge, utilized a laboratory model to test the combination of gemcitabine and nab-paclitaxel in pancreatic cancer.
“The combination has shown promise in an early clinical trial, and clinical results from a pivotal phase III trial will be reported in 2013,” said Tuveson. “However, we know very little about the mechanism of action because tumor samples have been so small.”
Using a laboratory model of metastatic pancreatic ductal adenocarcinoma, the researchers showed that combination treatment increased intratumoral gemcitabine levels due to a marked decrease in the primary gemcitabine metabolizing enzyme, cytidine deaminase.
Paclitaxel appeared to reduce these levels through reactive oxygen species-mediated degradation, resulting in increased stabilization of gemcitabine. Tuveson said understanding these mechanisms of action are important and will lead to better administration of the therapeutic combination if the larger human trials prove positive.
“For example, we predict from this mechanistic study that nab-paclitaxel may be most effective if we administer it first, and delay administration of the gemcitabine. The next step is to test this prediction, since it could help a great deal with patient treatment,” said Tuveson.
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Founded in 1907, the American Association for Cancer Research (AACR) is the world’s first and largest professional organization dedicated to advancing cancer research and its mission to prevent and cure cancer. AACR’s membership includes 34,000 laboratory, translational and clinical researchers; population scientists; other health care professionals; and cancer advocates residing in more than 90 countries. The AACR marshals the full spectrum of expertise of the cancer community to accelerate progress in the prevention, biology, diagnosis and treatment of cancer by convening more than 20 conferences and educational workshops, the largest of which is the AACR Annual Meeting with more than 18,000 attendees. In addition, the AACR publishes seven peer-reviewed scientific journals and a magazine for cancer survivors, patients and their caregivers. The AACR funds meritorious research directly as well as in cooperation with numerous cancer organizations. As the Scientific Partner of Stand Up To Cancer, the AACR provides expert peer review and scientific oversight of individual and team science grants in cancer research that have the potential for patient benefit. The AACR actively communicates with legislators and policy makers about the value of cancer research and related biomedical science in saving lives from cancer.
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