A New Chapter Has Opened in Pancreatic Cancer Treatment

The most common cancer of the pancreas is pancreatic adenocarcinoma, also called "exocrine pancreatic cancer". Pancreatic adenocarcinoma is among the top 5 causes of cancer-related death in Western countries and, in 2030, is expected to become, in the United States, the second leading cause of cancer-related deaths.

This is thought to have 2 main causes:

1. Obesity rates are rising, increasing the incidence of pancreatic cancer, and 
2. effective new treatments for pancreatic cancer have not yet been found. However, for many other cancers, particularly after 2010, numerous effective treatments of various types entered use (such as immune checkpoint inhibitors and targeted drugs).

Nevertheless, a new chemotherapy combination making a difference in pancreatic cancer treatment entered use after 2011 in stage 4 pancreatic cancer: the FOLFIRINOX regimen!

Surgery is the only chance of cure (complete recovery) for pancreatic cancer, but with pancreatic cancer surgery alone, 5-year survival rates are low (approximately % 10). Therefore, postoperative adjuvant (protective) chemotherapy is given, and this approach is known to reduce cancer recurrence rates. Until now, the standard chemotherapy drug for adjuvant treatment of pancreatic cancer has been a 6-month course of gemcitabine . Despite adjuvant treatment, within 2 years the proportion of patients experiencing relapse (recurrence) is between % 69 and 75. The combination of fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX), metastatic pancreatic cancer when used as first-line treatment, had previously been shown to provide superior overall survival compared with gemcitabine. Based on these findings, as adjuvant therapy after pancreatic cancer surgery, gemcitabine and modified-FOLFIRINOXwere compared for efficacy in a phase 3 clinical trial , and the results of this noteworthy study were published on 20 December 2018 in NEJM.

Note: In modified-FOLFIRINOX, compared with the standard regimen, the bolus fluorouracil dose has been removed to reduce adverse effects such as bone marrow suppression and diarrhea .

Details of the Study

The study evaluated 493 patients who had undergone pancreatic cancer surgery. Patients were randomly assigned to 2 arms;

• The experimental group received modified-FOLFIRINOX (oxaliplatin 85 mg/m2, irinotecan starting at 180 and reduced after safety analysis to 150 mg/m2, leucovorin 400 mg/m2 and fluorouracil 2400 mg/m2 every 14 days),
• The control group received gemcitabine (1000 mg/m2 on days 1, 8 and 15 every 4 weeks).
• Treatments continued for 24 weeks (6 months).
• The primary endpoint the study sought to measure was disease-free survival . Secondary endpoints were overall survival and safety.

Study Results

After a median follow-up of 33.6 months;

• Median disease-free survival in the modified-FOLFIRINOX group was 21.6 months , compared with the gemcitabine arm, where it was 12.8 months . Giving modified-FOLFIRINOX instead of gemcitabine reduced the risk of a cancer-related event, secondary cancer or death by % 42.
• At year 3, the disease-free survival rate was % 39.7 in the modified-FOLFIRINOX arm and % 21.4 in the gemcitabine arm.
• Median overall survival was 54.4 months in the modified-FOLFIRINOX arm and 35 months in the gemcitabine arm. Use of mofifiye-FOLFIRINOX reduced the risk of death by % 36.
• At year 3, overall survival rates were % 63.4 versus % 48.6.
• Severe (grade 3 and 4) adverse effects occurred in % 75.9 of those receiving modified-FOLFIRINOX and % 52.9 of those receiving gemcitabine (in the gemcitabine group, 1 patient died from an adverse effect called interstitial pneumonitis).

Conclusion

Set to change oncology practice, this valuable clinical study shows that in adjuvant pancreatic cancer treatment, modified-FOLFIRINOX provides significantly better survival than gemcitabine . However, this combination chemotherapy regimen also has a higher rate of adverse effects, which should not be forgotten.