Chemotherapy Before Surgery Extends Survival in Pancreatic Cancer
Patients with pancreatic cancer who received chemotherapy both before and after surgery experienced longer survival rates than would be expected from surgery followed by chemotherapy, according to a new study from researchers at Yale School of Medicine.
The study, published June 20 in JAMA Oncology, included patients with pancreatic ductal adenocarcinoma (PDAC), an aggressive cancer with a high mortality rate which accounts for 90% of pancreatic cancers. The researchers say these findings are encouraging for the 15 to 20% of patients with operable pancreatic cancer.
The single-arm Phase II trial evaluated a modified form of the chemotherapy treatment FOLFIRINOX. This combination treatment consisting of leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin received US Food and Drug Administration approval in 2011 as a first-line treatment for patients with metastatic pancreatic cancer. Patients in the trial received six cycles of the modified FOLFIRINOX before surgery, followed by an additional six cycles of the chemotherapy treatment after surgery. The modified regimen consisted of slightly lower doses of FOLFIRINOX to improve tolerability, which was previously shown in a 2016 publication not to impact outcomes negatively.
Of the 46 patients who started the modified treatment, 37 completed all six cycles of chemotherapy before surgery and 27 had successful tumour removal operations. For all enrolled patients, the 12-month progression-free survival rate was 67%, indicating significant progress in controlling the disease. Furthermore, 59% of all patients lived at least two years after completing the full chemotherapy treatment plan and surgery.
The study was the first of its kind for patients with PDAC when senior author and Yale Cancer Center member Jill Lacy, MD, started it in 2014. The study goal had been a 12-month progression-free survival rate of at least 50% of patients.
“When the study launched, even with operable pancreatic cancers, 90% of patients were still relapsing and dying from their cancer eventually,” said Michael Cecchini, MD, the first author of the study. “We sought to move chemotherapy up in their treatment regimen and give it before surgery to see if we could improve the outcome for our patients.”
The study used advanced techniques to monitor the progress of treatment, including analysing circulating tumour DNA (ctDNA) and using the cancer biomarker keratin 17 to help predict outcomes. For example, patients with detectable ctDNA four weeks post-surgery had significantly worse progression-free survival than those who had no detectable ctDNA.
Cecchini said larger randomised clinical trials are needed to continue to investigate the role of FOLFIRINOX before surgery for patients with operable PDAC.
“I think even though there have been changes in standard of care for patients with this aggressive pancreatic cancer type, we have here very promising data to justify a larger study,” said Cecchini.
Source: Yale School of Medicine
