Published online Dec 15, 2018. doi: 10.4251/wjgo.v10.i12.505
Peer-review started: September 19, 2018
First decision: October 15, 2018
Revised: October 24, 2018
Accepted: November 25, 2018
Article in press: November 26, 2018
Published online: December 15, 2018
Proper second-line treatment can improve survival of patients with unresectable pancreatic cancer (PC) who fail first-line treatment with gemcitabine (GEM)-based regimen. Although some previous phase III trials showed survival improvement with their study regimens, the standard second-line treatment remains unclear.
FOLFIRINOX, a standard first-line treatment for PC, has been proposed as a second-line treatment regimen; however, concerns about relatively high toxicity limited broad use of FOLFIRINOX as a second-line therapy.
We evaluated the efficacy and safety of modified dose of FOLFIRINOX as a second-line treatment for GEM-refractory unresectable PC.
In this prospective, multicenter, one-arm, open-label, phase II trial, unresectable PC patients, who showed disease progression during GEM-based therapy were enrolled. All patients were administered FOLFIRINOX with reduced irinotecan and oxaliplatin (RIO; irinotecan 120 mg/m2 and oxaliplatin 60 mg/m2), which was set according to the previous phase I study of FOLFIRINOX, with the standard dose of 5-fluorouracil (5-FU). The objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), overall survival (OS), adverse events, and changes in quality of life (QoL) were evaluated.
A total of 48 patients were enrolled in eight Korean centers. The ORR and DCR were 18.8% and 62.5%, respectively, including one patient who showed complete remission. The median PFS was 5.8 mo [95% confidence interval (CI): 3.7-7.9] and median OS was 9.0 mo (95%CI: 6.4-11.6). Neutropenia (64.6%) was the most common grade 3-4 adverse event. Although 14.6% of patients experienced grade 3 fatigue, most non-hematologic AEs were under grade 2. In the QoL analysis, the global health status score before treatment was not different from the score at the last visit after treatment (45.43 ± 22.88 vs 48.66 ± 24.14, P = 0.548).
FOLFIRINOX with RIO showed acceptable tolerability for patients in terms of patient QoL and may be considered as a treatment option in patients with GEM-refractory unresectable PC. However, the presence of hematologic toxicities should be carefully observed and the routine use of granulocyte colony-stimulating factor should be considered to minimize the risk of hematologic toxicities.
Prospective study with larger population comparing the efficacy and safety between FOLFIRINOX with RIO and 5-FU plus leucovorin needs to be conducted.