A medical and research team at Massachusetts General Hospital (MGH) Cancer Center published clinical trial results of a new treatment protocol for locally advanced pancreatic cancer (LAPC). The procedure combined intensive chemotherapy and radiation with the blood-pressure drug losartan. The research was published in the journal JAMA Oncology.
Locally advanced pancreatic cancer is a type that has grown into major blood vessels and as a result, can’t be removed safety via surgery (unresectable). The cancer has not yet metastasized outside the pancreas.
“Around 40% of pancreatic cancer patients have either locally advanced or borderline resectable disease, with historically poor rates of successful surgery,”Janet Murphy told The Harvard Gazette. Murphy is co-lead and corresponding author of the study, an instructor in medicine in the hematology/oncology division of Mass General’s Department of Medicine.
“To be able to successfully remove the primary tumor in 61% of patients sets a new benchmark and offers much hope,” she added. “To our knowledge, this is the first LAPC clinical trial that defined surgical success as its primary outcome.”
The new aspect of the procedure and the study is the addition of losartan, a drug for high blood pressure that is marketed as a generic form and under the brand name of Cozaar. Earlier studies by co-author Rakesh K. Jain, director of the Steele Laboratories for Tumor Biology at MGH and Andrew Werk Cook Professor of Radiation Oncology at Harvard Medical School, found that the drug improved chemotherapy delivery in animal models of breast, pancreatic and ovarian cancer. Its method of action for this is to relieve pressure in the tumor microenvironment that actually blocks drug delivery and decreases the oxygen supply, which is necessary for the tumor-killing activity of radiation therapy. Jain’s studies also indicated that cancer patients who were otherwise taking losartan or similar hypertension medications generally lived longer than others receiving the same types of cancer therapies.
In the current study, between August 2013 and July 2017, 49 MGH Cancer Center patients who had previously been untreated for LAPC received chemotherapy with a combination of fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX) for four months. They also took daily doses of losartan.
They then underwent CT scans to determine if the blood vessels were still involved with the tumors. Those whose blood vessels were no longer entangled received a short course of proton-beam radiation therapy. Those whose tumors still involved blood vessels received more conventional radiation therapy. Both groups continued to receive capecitabine chemotherapy during this post-CT period.
After this stage, 34 of the 49 patients had improved to where they could have their cancers removed. Thirty of the 34 patients’ cancers were successfully removed eliminating all evidence of cancer. For three patients, a pathologic complete response was observed, meaning no tumor was observed anywhere.
Biomarker studies also saw significant decreases in the expression of TGF-ß, showing that losartan was having the desired effect. Time until recurrence as well as overall survival time was significantly longer than was previously observed in LAPC patients.
“Locally advanced pancreatic cancer has been generally considered an incurable disease, so these results mark a dramatic improvement with respect both to rates of conversion to surgical resectability and to long-term disease outcomes,” co-lead author Jennifer Wo, assistant professor of radiation oncology, told The Harvard Gazette. “Based on these results we have launched a new, multi-institutional clinical trial that will also include the immunotherapy drug nivolumab [Bristol-Myers Squibb’s Opdivo), since losartan treatment has also been shown to activate several immune-system pathways.”
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