Effects of dose-modified FOLFIRINOX on toxicity and effectiveness in Japanese patients with unresectable pancreatic cancer (PC).

Abstract

480 Background: FOLFIRINOX has been shown superior to GEM in terms of OS, PFS and/or RR for treatment of metastatic PC in Accord 11, and this regimen has become the standard of care for the first-line chemotherapy. However, the major disadvantage of FOLFIRINOX is significantly higher toxicity, and, in particular, quite higher incidence of neutropenia(78%) and febrile neutropenia(22%) was observed in the PII clinical trial of FOLFIRINOX performed in Japan (LOHP-PII-05, JSCO 2013). Thus, in clinical practice for the Japanese patients, it should be needed to make modification on this regimen in terms of dose reduction without compromising in its effectiveness. We evaluated the safety and efficacy of modified(m) FOLFIRINOX in Japanese patients with unresectable locally advanced PC(LAPC) and/or metastatic PC(MPC). Methods: The modifications to FOLFIRINOX include discontinuation of the bolus 5-FU and dose-reduction(25%) of irinotecan. 20 patients with unresectable LAPC and/or MPC (PS 0-1) were treated with m FOLFIRINOX given every 2 weeks, and toxicity and efficacy were evaluated in these patients who received more than 3 courses. All patients did not receive prophylactic filgrastim. Results: Patient characteristics were as follows: LAPC/MPC 4/9; median age 65 yrs(range 39~75); male/female 15/5. Median number of cycles was 5.5 (range 1~17). Grade 3/4 toxicities included neutropenia(25%), nausea(30%), anorexia(35%) and diarrhea(20%). Grade 1/2 toxicities were sensory neuropathy(45%) and vomiting(40%). Febrile neutropenia was noted in 2 patients(10%). Toxic death was not observed, and 12 patients(60%) required dose reduction due to toxicity. Hematologic toxicities were decreased, however, those concerned with gastrointestinal toxicities were observed in a bit higher incidence compared to those in LOHP-PII-05. Response by CA19-9 was evaluable in 11 patients. 9 of 11 patients (82%) showed a decline in CA19-9 levels from baseline, and a greater than 50% decline was noted in 5 of 11 patients(45%). Conclusions: m FOLFIRINOX seems to have an improved safety profile even without prophylactic filgrastim and to maintain its efficacy.

Response to Y. Sasaki et al.: Is repeating FOLFIRINOX in the original dosage and treatment schedule tolerable in Japanese patients with pancreatic cancer?

“…Although several studies have been conducted to investigate the efficacy and safety of modified FOLFIRINOX regimens, the appropriate FOLFIRINOX regimen remains unclear. (5)(6)(7)(8)(9) Prospective studies of modified FOLFIRINOX regimens are being conducted in Japan, Europe and the USA. In the future, we anticipate the establishment of a modified FOLFIRINOX regimen that can control toxicity successfully without compromising efficacy.…”

“…Although several studies have been conducted to investigate the efficacy and safety of modified FOLFIRINOX regimens, the appropriate FOLFIRINOX regimen remains unclear 5–9. Prospective studies of modified FOLFIRINOX regimens are being conducted in Japan, Europe and the USA.…”