PMID- 32474564
OWN - NLM
STAT- MEDLINE
DCOM- 20200916
LR  - 20201030
IS  - 1423-0232 (Electronic)
IS  - 0030-2414 (Print)
IS  - 0030-2414 (Linking)
VI  - 98
IP  - 9
DP  - 2020
TI  - Oral S-1 with 24-h Infusion of Irinotecan plus Bevacizumab versus FOLFIRI plus 
      Bevacizumab as First-Line Chemotherapy for Metastatic Colorectal Cancer: An 
      Open-Label Randomized Phase II Trial.
PG  - 637-642
LID - 10.1159/000507293 [doi]
AB  - BACKGROUND: FOLFIRI plus bevacizumab have been widely used as first-line 
      treatment for metastatic colorectal cancer (mCRC). Pharmacokinetics and 
      pharmacodynamics suggested a low dose of irinotecan given as a long-term infusion 
      is expected to enhance antitumor activity. We conducted a randomized phase II 
      study to compare oral S-1 with a 24-h infusion of irinotecan plus bevacizumab 
      versus FOLFIRI plus bevacizumab. METHODS: The subjects comprised 120 
      chemotherapy-naive patients with mCRC. The study group received a 24-h infusion 
      of irinotecan at a dose of 125 mg/m2 on days 1 and 15, combined with oral S-1 80 
      mg/m2 on days 1-14 (24h-SIRI/B). The FOLFIRI/B group received irinotecan at a 
      dose of 150 mg/m2, 5-fluorouracil given at a dose of 400 mg/m2 as a bolus 
      injection and at a dose of 2,400 mg/m2 as a 46-h infusion, and 200 mg/m2 
      leucovorin on days 1 and 15. Bevacizumab was given at a dose of 5.0 mg/kg on days 
      1 and 15 in both groups. Treatment was repeated every 4 weeks. The primary 
      endpoint was 1-year progression-free survival (PFS). Secondary endpoints were 
      PFS, response rates (RR), overall survival (OS), and adverse events (AEs). 
      RESULTS: From December 2013 through January 2018, 120 patients were randomly 
      assigned, 61 patients to the 24h-SIRI/B and 59 patients to the FOLFIRI/B. The 
      median follow-up period was 22.8 months. The 1-year PFS rate was 43.14% in the 
      24h-SIRI/B arm and 19.15% in the FOLFIRI/B arm (HR = 0.312 [95%CI 0.13-0.78], p = 
      0.01). The median PFS was 10.2 months (95%CI 8.8-14.3) and 10.0 months (95%CI 
      7.4-11.0), and the median OS was 29.7 months (95%CI 22.9-43.9) and 28.8 months 
      (95%CI 18.4-ND), respectively (p = 0.3758, p = 0.8234). The overall RR was 86.3 
      and 61.7%, respectively (p = 0.0053). AEs were similar. CONCLUSIONS: Our results 
      show that the 24h-SIRI/B regimen is an effective and reasonably well-tolerated 
      regimen for the first-line treatment of mCRC.
CI  - (c) 2020 The Author(s) Published by S. Karger AG, Basel.
FAU - Sadahiro, Sotaro
AU  - Sadahiro S
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan, 
      sadahiro@is.icc.u-tokai.ac.jp.
FAU - Suzuki, Toshiyuki
AU  - Suzuki T
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
FAU - Okada, Kazutake
AU  - Okada K
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
FAU - Saito, Gota
AU  - Saito G
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
FAU - Miyakita, Hiroshi
AU  - Miyakita H
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
FAU - Ogimi, Takashi
AU  - Ogimi T
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
FAU - Chan, Lin Fung
AU  - Chan LF
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
FAU - Kamei, Yutaro
AU  - Kamei Y
AD  - Department of Surgery, Tokai University, School of Medicine, Isehara, Japan.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Randomized Controlled Trial
DEP - 20200529
PL  - Switzerland
TA  - Oncology
JT  - Oncology
JID - 0135054
RN  - 0 (Drug Combinations)
RN  - 150863-82-4 (S 1 (combination))
RN  - 1548R74NSZ (Tegafur)
RN  - 2S9ZZM9Q9V (Bevacizumab)
RN  - 5VT6420TIG (Oxonic Acid)
RN  - Q573I9DVLP (Leucovorin)
RN  - U3P01618RT (Fluorouracil)
RN  - XT3Z54Z28A (Camptothecin)
RN  - IFL protocol
SB  - IM
MH  - Administration, Oral
MH  - Adult
MH  - Aged
MH  - Antineoplastic Combined Chemotherapy Protocols/*administration & dosage
MH  - Bevacizumab/administration & dosage
MH  - Camptothecin/administration & dosage/analogs & derivatives
MH  - Colorectal Neoplasms/*drug therapy
MH  - Drug Administration Schedule
MH  - Drug Combinations
MH  - Female
MH  - Fluorouracil/administration & dosage
MH  - Humans
MH  - Infusions, Intravenous
MH  - Leucovorin/administration & dosage
MH  - Male
MH  - Middle Aged
MH  - Oxonic Acid/administration & dosage
MH  - Progression-Free Survival
MH  - Survival Rate
MH  - Tegafur/administration & dosage
MH  - Young Adult
PMC - PMC7592907
OTO - NOTNLM
OT  - 24-h infusion
OT  - Bevacizumab
OT  - Colorectal cancer
OT  - FOLFIRI
OT  - Irinotecan
OT  - Phase II study
OT  - S-1
COIS- All authors have no potential conflicts of interest to declare.
EDAT- 2020/06/01 06:00
MHDA- 2020/09/17 06:00
PMCR- 2020/05/29
CRDT- 2020/06/01 06:00
PHST- 2020/02/18 00:00 [received]
PHST- 2020/03/16 00:00 [accepted]
PHST- 2020/06/01 06:00 [pubmed]
PHST- 2020/09/17 06:00 [medline]
PHST- 2020/06/01 06:00 [entrez]
PHST- 2020/05/29 00:00 [pmc-release]
AID - 000507293 [pii]
AID - ocl-0098-0637 [pii]
AID - 10.1159/000507293 [doi]
PST - ppublish
SO  - Oncology. 2020;98(9):637-642. doi: 10.1159/000507293. Epub 2020 May 29.