TY - JOUR
T1 - Influence of initial dose intensity on efficacy of FOLFIRINOX in patients with advanced pancreatic cancer
AU - Kobayashi, Satoshi
AU - Ueno, Makoto
AU - Omae, Katsuhiro
AU - Kuramochi, Hidekazu
AU - Terao, Masato
AU - Mizuno, Nobumasa
AU - Ozaka, Masato
AU - Ueno, Hideki
AU - Uesugi, Kazuhiro
AU - Kobayashi, Noritoshi
AU - Kobayashi, Marina
AU - Todaka, Akiko
AU - Fukutomi, Akira
N1 - Publisher Copyright:
Copyright: Kobayashi et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2019/3/1
Y1 - 2019/3/1
N2 - The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard of care for advanced pancreatic cancer, but causes hematological and gastrointestinal toxicities, leading to treatment delay and dose reduction; optimal modification based on toxicities is needed. Therefore, we evaluated the effect of initial relative dose intensity (RDI) on FOLFIRINOX efficacy by conducting a Japanese nationwide survey. We evaluated overall survival (OS) and progression-free survival (PFS) of patients administered two or more cycles of FOLFIRINOX, and determined RDIs for each drug within the first two cycles. RDI's effect on efficacy was evaluated using a multivariate analysis with a Cox regression hazard model. Of 399 patients enrolled, 359 and 346 were evaluated for OS and PFS, respectively. Median RDI was 71.8%, 64.7%, 23.4%, and 76.9% for oxaliplatin, irinotecan, and bolus and continuous infusions of 5-FU, respectively. A high RDI for 5-FU bolus resulted in poor prognosis in terms of PFS (hazard ratio: 1.34; p = 0.022) and negatively correlated with objective response (coefficient: −0.70; p = 0.021), and a high RDI for CPT-11 positively correlated with objective response (coefficient: 1.02; p = 0.031). In conclusion, low and high RDIs for irinotecan and 5-FU bolus, respectively, resulted in poor FOLFIRINOX efficacy.
AB - The combination of fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX) is the standard of care for advanced pancreatic cancer, but causes hematological and gastrointestinal toxicities, leading to treatment delay and dose reduction; optimal modification based on toxicities is needed. Therefore, we evaluated the effect of initial relative dose intensity (RDI) on FOLFIRINOX efficacy by conducting a Japanese nationwide survey. We evaluated overall survival (OS) and progression-free survival (PFS) of patients administered two or more cycles of FOLFIRINOX, and determined RDIs for each drug within the first two cycles. RDI's effect on efficacy was evaluated using a multivariate analysis with a Cox regression hazard model. Of 399 patients enrolled, 359 and 346 were evaluated for OS and PFS, respectively. Median RDI was 71.8%, 64.7%, 23.4%, and 76.9% for oxaliplatin, irinotecan, and bolus and continuous infusions of 5-FU, respectively. A high RDI for 5-FU bolus resulted in poor prognosis in terms of PFS (hazard ratio: 1.34; p = 0.022) and negatively correlated with objective response (coefficient: −0.70; p = 0.021), and a high RDI for CPT-11 positively correlated with objective response (coefficient: 1.02; p = 0.031). In conclusion, low and high RDIs for irinotecan and 5-FU bolus, respectively, resulted in poor FOLFIRINOX efficacy.
KW - Dose response relationship
KW - Fluorouracil
KW - Irinotecan
KW - Leucovorin
KW - Oxaliplatin
UR - http://www.scopus.com/inward/record.url?scp=85062763846&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.26633
DO - 10.18632/oncotarget.26633
M3 - Article
C2 - 30956757
AN - SCOPUS:85062763846
SN - 1949-2553
VL - 10
SP - 1775
EP - 1784
JO - Oncotarget
JF - Oncotarget
IS - 19
ER -