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Adding Blood Pressure Drug to Chemo May Spark Immune Response in Advanced Pancreatic Cancer

A combination of the blood pressure medication, Cozaar, to a chemo regimen is more effective in reducing genes related to immunosuppression and invasion than chemo alone, study results show.

Patients receiving neoadjuvant (treatment administered before surgery) chemotherapy and chemoradiation for locally advanced pancreatic cancer saw a greater immune response and reduction of tumor size when treated with the blood pressure drug Cozaar (losartan) as opposed to chemo alone.

Pancreatic cancer accounts for 3% of cancer diagnoses in the United States but is responsible for 7% of all cancer deaths, according to the American Cancer Society. Treatment options for the disease are currently quite limited, especially so for patients whose disease is locally advanced (spread to the tissue surrounding the initial tumor) or metastatic (spread to a distant location).

Chemotherapy and radiation do not often cure pancreatic cancer, so surgery is needed to excise cancerous cells. This poses a challenge for patients with locally advanced disease, as the chances of removing all cancerous cells decreases when disease advances past the initial tumor site.

“Patients with advanced pancreatic cancer, they are not amenable to surgery because the tumor impinges on surrounding big vessels and other tissues,” said Yves Boucher, study author and associate professor of radiation oncology at Massachusetts General Hospital in Boston, in an interview with CURE®. “So what the clinicians do (is) treat (the cancer cells) with cytotoxic therapies. The hope there is that you would reduce the size of the tumor and reduce the invasion of surrounding blood vessels. That's why people receive what's called neoadjuvant chemotherapy.”

Boucher explained that the blood pressure medication could help reduce the invasion of cancer cells to surrounding tissues as well as reduce the activity of immunosuppressive cells.

“Essentially, we found that, in resected lesions that were treated with (Cozaar), the cancer cells were most likely less invasive, genes related to invasion were downregulated,” he said. “The lower expression of several invasive genes was related to better survival of the patients. We also found that immunosuppressive genes were downregulated and in lesions with a good treatment response there was less immunosuppressive cells. So that would mean that the immune system could work better because there's less immunosuppression.”

Tumors often produce proteins that suppress the immune system. This makes it easier for the tumor to grow and spread while reducing the chances the body will kill tumor cells, so adding a medication to negate immunosuppression gives patients a better chance at disease eradication.

This study specifically paired Cozaar with a chemotherapy cocktail referred to as FOLFIRINOX (folinic acid, fluorouracil, irinotecan, and oxaliplatin) and included chemoradiation treatment afterwards. Side effects associated with the treatment regimen include neutropenia, thrombocytopenia, diarrhea, nausea/vomiting and peripheral neuropathy (damage to peripheral nerves). While side effects were severe in some cases, no treatment-related deaths have been recorded.

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