FOLFIRINOX regimen better than older chemo after surgery for pancreatic cancer

Last Updated: 2018-12-19

By Gene Emery

(Reuters Health) - Six months of postoperative treatment for pancreatic cancer with a four-drug combination once restricted to later stages of the disease offers better survival than conventional gemcitabine therapy, according to preliminary results from the PRODIGE-24 study of nearly 500 patients published December 19 online in The New England Journal of Medicine.

But the discovery is not expected to benefit most pancreatic cancer patients because fewer than 20% are candidates for surgery by the time their tumor is discovered.

The treatment is a combination of fluorouracil, leucovorin, irinotecan and oxaliplatin known as FOLFIRINOX. The research team, led by Thierry Conroy at the Lorraine Institute of Oncology in France, modified the treatment by eliminating bolus fluorouracil in an attempt to reduce its toxicity.

Median disease-free survival was 21.6 months with FOLFIRINOX versus 12.8 months with gemcitabine (P<0.001).

Overall survival rates at three years were 63.4% and 48.6% respectively.

"The median overall survival of 54.4 months in the experimental group is truly unprecedented among patients with this disease," said Dr. Hedy Kindler, professor of medicine at University of Chicago Medicine, in a Journal editorial.

FOLFIRINOX "has been much more effective" than originally projected when the study began, Prof. Conroy told Reuters Health in a telephone interview. "These are very good results and we had manageable toxicities."

The odds of developing grade 3- or -4 adverse events were far higher with FOLFIRINOX group (75.9%) than with gemcitabine (52.9%).

Serious problems that occurred more frequently in the modified-FOLFIRINOX group included diarrhea, paresthesia, fatigue, nausea, vomiting, abdominal pain, mucositis, sensory peripheral neuropathy and higher gamma-glutamyl transferase levels. Higher-grade thrombocytopenia was more common with gemcitabine.

The Conroy team said the poorer safety profile was expected.

The study did not assess quality of life. But Prof. Conroy said that in previous studies of FOLFIRINOX, patients with metastatic disease reported improved quality of life despite the side effects.

Dr. William Hawkins, chief of hepatobiliary-pancreatic and gastrointestinal surgery at Washington University School of Medicine in St. Louis, Missouri, who was not involved in the study, thinks the new results will not dramatically affect care in the United States because doctors are already giving the treatment to patients who can tolerate it.

"We have a long way to go because only 20% can have surgery and only a select group of patients can have these harsh drugs," he told Reuters Health by phone.

Pancreatic cancer is one of the hardest to cure, with a success rate of just 8%. Even when surgery is considered curative, fewer than 4% live 10 years. Nearly 44,000 people die from it in the U.S. each year.

"Within the next decade, pancreatic cancer is projected to become the second leading cause of death from cancer in the United States, which reflects the inadequacy of our current treatment options," Dr. Kindler said.

Seventy -seven hospitals in France and Canada were involved in the new test.

All the volunteers had histologically confirmed pancreatic ductal adenocarcinoma with no residual tumor or microscopic residual tumor after resection. Their CA 19-9 levels were below 181. The study was terminated prematurely because the findings were so significant.

"A cancer-related event, second cancer, or death occurred in 134 patients (54.3%) in the modified-FOLFIRINOX group and in 180 (73.2%) in the gemcitabine group," the Conroy team reported.

Disease-free survival rates for FOLFIRINOX versus gemcitabine were 69.0% and 53.7% respectively at one year, 47.0% and 30.7% at two years, and 39.7% and 21.4% at three years.

Age did not affect the effectiveness of therapy.

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Dr. Kindler said researchers may want to try giving FLOFIRINOX therapy before surgery to see if that improves outcomes.

Prof. Conroy said that he knows of two randomized studies that are already testing the idea.

Dr. Hawkins said many doctors in the U.S. are already giving the therapy first in an attempt to shrink the tumor enough to be resected.

"If their tumor is that aggressive, we avoid this great big operation that would probably not help them," he said. "If we do the surgery first, we lose a lot of patients who are too sick to have this chemotherapy."

For now, "The remarkable results that have been achieved with adjuvant modified FOLFIRINOX therapy in the PRODIGE 24 trial have now changed the standard of care for many patients with resectable tumors," Dr. Kindler said. "However, the majority of patients with pancreatic cancer present with far more advanced disease. For them, this remains a recalcitrant cancer."

SOURCE: https://bit.ly/2A2WVbv

N Engl J Med 2018.