By David Douglas
NEW YORK (Reuters Health) - 7/6/2019
In the majority of studied patients with locally advanced pancreatic cancer, total neoadjuvant treatment with fluorouracil, leucovorin, oxaliplatin and irinotecan (FOLFIRINOX) along with losartan and chemoradiation allowed complete tumor removal, according to a single-arm phase 2 trial.
"Around 40 percent of pancreatic cancer patients have either locally advanced or borderline resectable disease, with historically poor rates of successful surgery," Dr. Janet Murphy of Harvard Medical School, in Boston, said in a statement. "To be able to successfully remove the primary tumor in 61 percent of patients sets a new benchmark and offers much hope."
There is evidence that FOLFIRINOX can downstage the disease, Dr. Murphy and colleagues note in JAMA Oncology, online May 30. Angiotensin-I-receptor blockers such as losartan, they add, may "both reduce the malignant potential of cancer cells and alter the tumor microenvironment, activating immunity and normalizing the extracellular matrix to allow for enhanced delivery of cytotoxic chemotherapy."
The researchers studied 49 previously untreated patients. All had been determined by multidisciplinary review to have locally advanced unresectable pancreatic cancer; 38 were given FOLFIRINOX and losartan for eight cycles, while the remainder had fewer cycles due to disease progression, losartan intolerance or toxicity.
Thirty-eight patients went on to have long-term chemoradiotherapy and seven had short-term chemoradiotherapy. Surgical exploration was conducted in 42 patients and 34 underwent resection. R0 resection was achieved in 30 of these (88%) and overall in 61% of eligible participants.
Twenty-seven patients were still alive at study completion, representing a median follow-up of 17.1 months.
In patients who underwent resection, median progression-free survival was 21.3 months compared to 17.5 months in those who did not. Corresponding proportions for overall survival were 33.0 months and 31.4 months.
Dr. Murphy told Reuters Health by email that "locally advanced pancreatic cancer is a historically incurable disease. Publishing a study with a primary endpoint of surgical resection speaks to how far we have moved the needle."
She added that her team attributes the 61% R0 resection rate to the combination of highly active chemotherapy, tailored radiation and an aggressive surgical approach.
"We posit that the addition of losartan was instrumental in our outcome, a question we are exploring in a current randomized trial," Dr. Murphy said.
JAMA Oncol 2019.