Pancreatic cancer patients who received chemotherapy before and after surgery had longer survival rates compared to those who had surgery followed by chemotherapy.
That is according to new research published in JAMA Oncology and by Yale Cancer Centre and Yale School of Medicine.
The study included patients with pancreatic ductal adenocarcinoma (PDAC), which accounts for 90% of pancreatic cancers.
An aggressive cancer with a high mortality rate, PDAC is predicted to become the second leading cause of cancer-related deaths in the US by 2030.
Results are encouraging for the 15 to 20% of pancreatic cancer patients whose tumours are operable.
The single-arm (only one treatment type or regimen) Phase II trial evaluated a modified form of the chemotherapy treatment FOLFIRINOX (a combination treatment consisting of leucovorin calcium, fluorouracil, irinotecan hydrochloride, and oxaliplatin approved 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 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 — meaning the disease did not worsen – was 67%, indicating significant progress in controlling the disease. Furthermore, 59% of all patients lived at least two years after completing the chemotherapy treatment plan and surgery.
When senior author and YCC member Dr Jill Lacy started the study in 2014, it was the first of its kind for patients with PDAC. The study goal was a 12-month progression-free survival rate of at least 50% of patients.
Dr Michael Cecchini, the first author of the study and the co-director of the colorectal program at the Center for Gastrointestinal Cancers at Smilow Cancer Hospital and YCC, said: ‘When the study launched, even with operable pancreatic cancers, 90% of patients were still relapsing and dying from their cancer eventually. 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 treatment progress, 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 without detectable ctDNA.
Cecchini said more extensive randomised clinical trials are needed to continue investigating the role of FOLFIRINOX before surgery for patients with operable PDAC.
‘Even though there have been changes in the standard of care for patients with this aggressive pancreatic cancer type, we have very promising data to justify a larger study.’
