MedicalResearch.com Interview with:
Rajesh Kumar NV, Ph.D.
Instructor of Oncology and Pathology
Johns Hopkins University School of Medicine
Baltimore, MD, USA
Current Affiliation: Senior Manager, Human Therapeutics Division, Intrexon Corporation, 20358 Seneca Meadows Parkway, Germantown, MD, USA
MedicalResearch.com: What is the background for this study?
Response: Pancreatic cancer remains as one of the most deadly malignancies in the world. Recently, a cremophor-free and albumin-bound formulation of paclitaxel (nab-PTX, Abraxane) in combination with gemcitabine (GEM, Gemzar) is recently approved as a standard of care treatment option for patients with metastatic pancreatic cancer. Majority of the newly diagnosed pancreatic cancer patients use the nab-PTX plus GEM regimen. Currently there are over 100 clinical trials at various stages with this regimen as a backbone to approved medicines or investigational agents. Since widely available cremophor-based paclitaxel (PTX, Taxol) is a key chemotherapy component for the treatment of several human malignancies and the treatment cost of nab-PTX is relatively higher than PTX, patients, clinicians, third party payers and regulatory agencies have a substantial interest in understanding whether these two drugs provide a similar level of therapeutic efficacy in pancreatic cancer.
We utilized orthotopic models of human pancreatic cancer, which were shown to better recapitulate the histologic and metastatic characteristics of disease, and compared the anticancer efficacy, effect on tumor stroma modulation, metastatic spreading to distant organs and survival following GEM, PTX, nab-PTX and combinations of GEM plus PTX or nab-PTX. The preclinical trial used a total of 300 mice with established orthotopic pancreatic tumors. The tumors used for implantation were originally resected from the primary tumors of patients with moderately differentiated and poorly differentiated pancreatic cancer.
MedicalResearch.com: What are the main findings?
Response: Our results demonstrated that therapeutic efficacy of nab-PTX and PTX vary widely. Nab-PTX treatment resulted in significantly higher paclitaxel tumor plasma ratio, remarkably effective in blocking primary tumor progression, depletion of dense tumor stroma and consistently achieved greater antitumor response, resulting in enhanced survival of tumor harboring animals compared to PTX treatment. Combined treatment of GEM plus nab-PTX decreased metastatic tumor burden and increased overall survival of animals when compared to either agent used alone. These therapeutic effects were accompanied by depletion of dense fibrotic tumor stroma and decreased proliferation of carcinoma cells.
MedicalResearch.com: What should readers take away from your report?
Response: Therapeutic efficacy of nab-paclitaxel was superior to paclitaxel in pancreatic cancer. Nab-paclitaxel monotherapy was equivalent to nab-paclitaxel plus gemcitabine combination in providing survival advantage to mice with established orthotopic tumors in a highly aggressive metastatic pancreatic cancer model. Nab-paclitaxel prevented the progression of aggressive pancreatic cancer, indicating its potential utility as a backbone to approved drugs or investigational agents. The addition of paclitaxel to gemcitabine showed no survival advantage over gemcitabine treatment, concluding that a clinical combination of paclitaxel and gemcitabine may unlikely to provide significant survival advantage over gemcitabine monotherapy and may not be a viable alternative to the nab-paclitaxel plus gemcitabine regimen for the treatment of pancreatic cancer patients.
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Br J Cancer. 2016 Aug 9;115(4):442-53. doi: 10.1038/bjc.2016.215. Epub 2016 Jul 21.
Superior therapeutic efficacy of nab-paclitaxel over cremophor-based paclitaxel in locally advanced and metastatic models of human pancreatic cancer.
Rajeshkumar NV1,2, Yabuuchi S2, Pai SG2, Tong Z3, Hou S4, Bateman S5, Pierce DW6, Heise C6, Von Hoff DD7, Maitra A8,9, Hidalgo M10.
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