Clinical Pearls & Morning Reports
Published December 19, 2018
Pancreatic adenocarcinoma is a major cause of cancer-related death in Western countries and is anticipated to emerge as the second leading cause of cancer-related death in the United States by 2030. Conroy et al. conducted a phase 3 trial to explore the efficacy of FOLFIRINOX, as compared with gemcitabine, as adjuvant therapy after resection of pancreatic cancer. A modified version of the FOLFIRINOX regimen, without bolus fluorouracil, was used to decrease the incidence and severity of hematologic toxic effects and diarrhea. Read the Latest NEJM Original Article here.
Q: What are the components of FOLFIRINOX?
A: FOLFIRINOX is a drug combination that includes fluorouracil, leucovorin, irinotecan, and oxaliplatin; FOLFIRINOX has resulted in longer overall survival than gemcitabine when administered as first-line treatment in patients with metastatic pancreatic cancer.
Q: What adjuvant therapies are currently used for pancreatic ductal cancer?
A: Surgery offers the only chance of cure, but 5-year survival rates after surgical resection alone are low (approximately 10%). A 6-month regimen of adjuvant therapy with gemcitabine or a fluoropyrimidine (fluorouracil plus leucovorin or S-1 in Japan) has been shown to significantly improve outcomes and is recognized as standard care in patients with resected pancreatic cancer. However, recurrence rates remain high despite adjuvant treatment, with 69 to 75% of patients having a relapse within 2 years.
A: In the trial by Conroy et al., adjuvant chemotherapy with a modified FOLFIRINOX regimen led to significantly longer disease-free survival, overall survival, metastasis-free survival, and cancer-specific survival than treatment with gemcitabine. The median disease-free survival (primary end point) was significantly longer, by 8.8 months, in the modified-FOLFIRINOX group than in the gemcitabine group. The disease-free survival benefit with modified FOLFIRINOX was significant in the majority of subgroups, including subgroups of patients with adverse prognostic factors (i.e., T3 or T4 tumor status, positive lymph nodes, or R1 [cancer cells seen microscopically at the resection margin] resection). Overall survival was significantly longer by 19.4 months in the modified-FOLFIRINOX group than in the gemcitabine group, with a similar duration of follow-up in each group. However, the data remain immature, with 61% of all the patients being alive at the time of analysis. The trial is ongoing, with 3 years of follow-up currently.
A: The incidence of toxic effects was higher with the modified FOLFIRINOX regimen than with gemcitabine therapy. Adverse events of grade 3 or 4 were reported in 75.9% in the modified-FOLFIRINOX group and in 52.9% in the gemcitabine group, and grade 4 events were reported in 29 patients (12.2%) and 29 patients (12.0%), respectively. The incidence of grade 3 or 4 events of diarrhea, changes in the γ-glutamyltransferase level, paresthesia, fatigue, sensory peripheral neuropathy, nausea, vomiting, abdominal pain, and mucositis was significantly higher in the modified-FOLFIRINOX group, whereas thrombocytopenia of grade 3 or 4 was significantly more common in the gemcitabine group.