An update to the American Society of Clinical Oncology (ASCO) clinical practice guideline on the management of patients with potentially curative pancreatic cancer identified the combination chemotherapy regimen of 5-fluorouracil (without bolus administration), oxaliplatin, and irinotecan (modified FOLFIRINOX, also known as mFOLFIRINOX) as the preferred adjuvant therapy for patients with pancreatic adenocarcinoma who have undergone an R0 or R1 resection and have not received neoadjuvant chemotherapy. This new recommendation was added to the previously published ASCO clinical practice guideline covering the management of these patients, and is published in the Journal of Clinical Oncology.1
In the phase 3 PRODIGE 24/Canadian Cancer Trials Group (CCTG) PA.6 trial (ClinicalTrials.gov Identifier: NCT01526135), patients aged 18 to 79 years with resected (R0 or R1) pancreatic adenocarcinoma who had not received prior chemotherapy or radiation therapy were randomly assigned to receive 6 months of adjuvant therapy with either gemcitabine or mFOLFIRINOX.2
Median disease-free survival, the primary end point of the study, was significantly prolonged for patients receiving mFOLFIRINOX compared with gemcitabine monotherapy (21.6 months versus 12.8 months; hazard ratio [HR], 0.58; 95% CI, 0.46-0.73; P <.001). Furthermore, median overall survival, a secondary end point of the study, was 54.4 months and 35.0 months for those receiving mFOLFIRINOX and gemcitabine, respectively (HR, 0.64; 95% CI, 0.48-0.86; P =.003).
Grade 3/4 adverse events were more frequent in the mFOLFIRINOX arm compared with the gemcitabine arm (75.9% versus 52.9%), including fatigue, diarrhea, nausea, vomiting, abdominal pain, sensory peripheral neuropathy, paresthesia, mucositis, and increased γ-glutamyltransferase level.More patients receiving gemcitabine experienced grade 3/4 thrombocytopenia (1.3% versus 4.5%). 2
Based on these results, the current version of the ASCO clinical practice guideline specifies that “all patients with resected pancreatic adenocarcinoma who did not receive preoperative therapy should be offered 6 months of adjuvant chemotherapy in the absence of medical or surgical contraindications. The modified combination regimen mFOLFIRINOX as used in the latter part of the PRODIGE 24/CCTG PA.6 trial (oxaliplatin 85 mg/m2, leucovorin 400 mg/m2, irinotecan 150 mg/m2 D1, and 5-fluorouracil 2.4 g/m2 over 46 hours every 14 days for 12 cycles) is preferred in the absence of concerns for toxicity or tolerance; alternatively, doublet therapy with gemcitabine and capecitabine or monotherapy with gemcitabine alone or fluorouracil plus folinic acid alone can be offered.”
- Khorana AA, McKernin SE, Berlin J, et al. Potentially curable pancreatic adenocarcinoma: ASCO clinical practice guideline update [published online June 10, 2019]. J Clin Oncol. doi: 10.1200/JCO.19.00946
- Conroy T, Hammel P, Hebbar M, et al. FOLFIRINOX or gemcitabine as adjuvant therapy for pancreatic cancer. N Engl J Med. 2018;379(25):2395-2406.