Effect of FOLFIRINOX as second-line chemotherapy for metastatic pancreatic cancer after gemcitabine-based chemotherapy failure

Abstract

Background: This study aimed to determine the maximum tolerated dose (MTD), dose-limiting toxicity, and efficacy of second-line chemotherapy with FOLFIRINOX after gemcitabine (GEM)-based chemotherapy failure in metastatic pancreatic cancer (MPC).

Methods: We studied 18 histopathologically proven MPC patients. The schedule was 85 mg/m oxaliplatin, irinotecan, and 400 mg/m leucovorin, followed by 400 mg/m 5-fluorouracil (5-FU) as a bolus on day 1 and 2400 mg/m 5-FU as a 46-hour continuous infusion biweekly. The dose of irinotecan was defined as follows: level 0: 100 mg/m, level 1: 125 mg/m, level 2: 150 mg/m, and level 3: 180 mg/m. The doses of other drugs were fixed. The primary endpoint of phase II study was the response rate (RR).

Results: We initially evaluated 6 patients in a phase I study. One patient developed neutropenia and 1 patient developed hyperglycemia and severe infection. Accordingly, level 1 was chosen as the MTD. According to a phase II study, the RR was 22.2% and the disease control rate was 61.1%. The progression-free survival and overall survival were 2.8 (range, 0.7-19.1) and 9.8 (2.4-19.8) months, respectively. The most common severe adverse event was neutropenia (66.7%). Febrile neutropenia occurred in 1 (5.6%) case.

Conclusion: The recommended dose was 85 mg/m oxaliplatin, 100 mg/m irinotecan, and 400 mg/m leucovorin, followed by 400 mg/m 5-FU as a bolus on day 1 and 2400 mg/m 5-FU as a 46-hour continuous infusion. These results indicate that second-line FOLFIRINOX is a marginally effective treatment for GEM-based chemotherapy failure cases.

Figure 1

Kaplan–Meier analysis of progression-free survival in a phase II study of FOLFIRINOX as second-line chemotherapy for unresectable pancreatic cancer after gemcitabine-based chemotherapy failure. The median progression-free survival was 2.8 months (95% confidence interval, 2.3–3.1). No patient data were censored.

Figure 2

Kaplan–Meier analysis of overall survival in a phase II study of FOLFIRINOX as second-line chemotherapy for unresectable pancreatic cancer after gemcitabine-based chemotherapy failure. The median survival was 9.8 months (95% confidence interval, 6.4–13.1). No patient data were censored.

Figure 3

Kaplan–Meier analysis of overall survival from first-line treatment in a phase II study of FOLFIRINOX as second-line chemotherapy for unresectable pancreatic cancer after gemcitabine-based chemotherapy failure. The median survival was 15.5 months (95% confidence interval, 9.0–21.9). No patient data were censored.