Chemotherapy regimen extends life by nearly 20 months

<p class="article-intro">In a randomized phase-III-trial people with surgically removed pancreatic cancer who received mFOLFIRINOX lived a median of 20 months longer and were cancer-free nine months longer than those who received the current standard of care, gemcitabine.</p> <hr /> <p class="article-content"><p>The PRODIGE 24/CCTG PA.6 trial enrolled patients with non-metastatic pancreatic ductal adenocarcinoma (PDAC) who had surgery that removed all or nearly all of the tumor meaning no cancer cells visible to the surgeon after surgery, but microscopic tumoral cells may have remained. Three to 12 weeks after surgery, 493 patients were randomly assigned in France and in Canada to receive either gemcitabine or mFOLFIRINOX (oxaliplatin, leucovorin, irinotecan and 5-fluorouracil) for six months.</p> <p>At a median follow-up of 33,6 months, the median length of time without recurrence of pancreatic cancer (disease-free survival) was much longer in the mFOLFIRINOX group than in the gemcitabine group (21,6 months vs. 12,8 months), as was the median overall survival (54,4 months with mFOLFIRINOX vs. 35,0 months with gemcitabine). The benefit of the mFOLFIRINOX is observed in all subgroups of patients. mFOLFIRINOX also markedly extended the time until metastases appeared (median 30,4 months vs. 17,0 months with gemcitabine). <br />Overall, more patients experienced severe side effects (mainly hematologic) in the mFOLFIRINOX group than in the gemcitabine group (76 % vs. 53 % ), but the side effects were manageable, according to the authors. One treatment-related death occurred in the gemcitabine group, and none in the mFOLFIRINOX group. <br />The types of side effects also differed between the two groups. The most common side effects of gemcitabine were headache, fever, flu-like symptoms, swelling, and low white blood cell counts. Patients who received mFOLFIRINOX had more diarrhea, nausea, vomiting, and fatigue. There was no difference in the risk of febrile neutropenia between the two groups. <br />Past medical history of ischemic heart disease represents a risk with either regimen, but particularly mFOLFIRINOX. Patients should be assessed for underlying heart disease before starting this adjuvant treatment.</p> <p>The next step will be to explore the timing of chemotherapy. Patients may benefit from receiving neoadjuvant chemotherapy to shrink the tumor, to destroy undetectable micrometastases and increase the chance that the tumor can be completely removed through surgery. Another option is to give half the cycles of chemotherapy before, and the other half after surgery. Ongoing clinical trials are already testing both of these approaches.</p> <p><strong>Reference:</strong> <br />Conroy T et al.: Unicancer GI PRODIGE 24/CCTG PA.6 trial: A multicenter international randomized phase III trial of adjuvant mFOLFIRINOX versus gemcitabine (gem) in patients with resected pancreatic ductal adenocarcinomas. ASCO Annual Meeting 2018, abstract #LBA4001</p></p>