PMID- 33330814
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201218
IS  - 2434-9194 (Electronic)
IS  - 2434-9186 (Print)
IS  - 2434-9186 (Linking)
VI  - 2
IP  - 4
DP  - 2020 Aug 31
TI  - Impact of sex and histology on the therapeutic effects of fluoropyrimidines and 
      oxaliplatin plus bevacizumab for patients with metastatic colorectal cancer in 
      the SOFT trial.
PG  - 240-246
LID - 10.35772/ghm.2020.01050 [doi]
AB  - Mechanisms accounting for sex differences in the incidence of adverse events 
      caused by fluoropyrimidine treatments, and histologic differences in efficacy are 
      insufficiently understood. We determined differences between the sexes in terms 
      of the safety of S-1 plus oxaliplatin (SOX)/bevacizumab-versus-l-leucovorin, 
      5-fluorouracil (5-FU) and oxaliplatin (FOLFOX)/bevacizumab, and the impact of 
      histology on their therapeutic effects, in 512 unresectable metastatic colorectal 
      cancer patients from the SOFT phase III study. Nausea (OR: 2.88, P < 0.001) and 
      vomiting (OR: 3.04, P = 0.005) occurred more frequently in females than males 
      treated with SOX/bevacizumab, while nausea (OR: 2.12, P = 0.006), vomiting (OR: 
      3.26, P = 0.004), leukopenia (OR: 2.61, P < 0.001), neutropenia (OR: 2.92, P < 
      0.001), and alopecia (OR: 4.13, P < 0.001) were higher in females on 
      FOLFOX/bevacizumab. Mean relative dose intensities (RDIs) of S-1 during all 
      cycles of SOX/bevacizumab were significantly lower in females (73.9%) than males 
      (81.5%) (P < 0.001), while RDIs of continuous infusion of 5-FU in the 
      FOLFOX/bevacizumab regimen were 75.0% in females and 80.5% in males (P = 0.005). 
      No significant differences in efficacy with regard to overall survival (OS) and 
      progression-free survival (PFS) were identified between the sexes for either 
      SOX/bevacizumab or FOLFOX/bevacizumab treatment. Patients with 
      poorly-differentiated adenocarcinoma had significantly worse OS (HR: 2.72, 95% 
      CI: 1.67-4.44, P < 0.0001) and PFS (HR: 1.89, 95% CI: 1.18-3.02, P = 0.0079) than 
      patients with well- or moderately-differentiated adenocarcinoma. Female patients 
      experienced more frequent and severe adverse reactions to SOX/bevacizumab and 
      FOLFOX/bevacizumab and a worse prognosis for poorly-differentiated adenocarcinoma 
      were confirmed in this phase III study. This warrants further translational 
      research to identify the responsible mechanisms.
CI  - 2020, National Center for Global Health and Medicine.
FAU - Yamada, Yasuhide
AU  - Yamada Y
AD  - Gastrointestinal Medical Oncology Division, National Cancer Center Hospital, 
      Tokyo, Japan.
FAU - Muro, Kei
AU  - Muro K
AD  - Department of Clinical Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi, 
      Japan.
FAU - Takahashi, Keiichi
AU  - Takahashi K
AD  - Department of Surgery, Tokyo Metropolitan Cancer and Infectious Diseases Center, 
      Komagome Hospital, Tokyo, Japan.
FAU - Baba, Hideo
AU  - Baba H
AD  - Department of Gastroenterological Surgery, Kumamoto University, Kumamoto, Japan.
FAU - Komatsu, Yoshito
AU  - Komatsu Y
AD  - Cancer Center, Hokkaido University Hospital, Sapporo, Hokkaido, Japan.
FAU - Satoh, Taroh
AU  - Satoh T
AD  - Department of Frontier Science for Cancer and Chemotherapy, Osaka University, 
      Osaka, Japan.
FAU - Goto, Masahiro
AU  - Goto M
AD  - Cancer Center, Osaka Medical College Hospital, Osaka, Japan.
FAU - Mishima, Hideyuki
AU  - Mishima H
AD  - Aichi Medical University, Nagakute, Aichi, Japan.
FAU - Watanabe, Masahiko
AU  - Watanabe M
AD  - Kitasato University Kitasato Institute Hospital, Tokyo, Japan.
FAU - Sakata, Yuh
AU  - Sakata Y
AD  - Misawa City Hospital, Misawa, Aomori, Japan.
FAU - Morita, Satoshi
AU  - Morita S
AD  - Kyoto University, Kyoto, Japan.
FAU - Shimada, Yasuhiro
AU  - Shimada Y
AD  - Kochi Health Sciences Center, Kochi, Japan.
FAU - Takenaka, Naruhito
AU  - Takenaka N
AD  - Taiho Pharmaceutical Co. Ltd., Tokyo, Japan.
FAU - Hirooka, Tadashi
AU  - Hirooka T
AD  - Taiho Pharmaceutical Co. Ltd., Tokyo, Japan.
FAU - Sugihara, Kenichi
AU  - Sugihara K
AD  - Tokyo Medical and Dental University, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PL  - Japan
TA  - Glob Health Med
JT  - Global health & medicine
JID - 101771579
PMC - PMC7731258
OTO - NOTNLM
OT  - S-1
OT  - bevacizumab
OT  - fluorouracil
OT  - gender
OT  - poorly differentiated adenocarcinoma
COIS- YY has received honoraria from Taiho, Chugai, Nipponkayaku, Japan. KM has 
      received honoraria from Eli Lilly, Chugai, Takeda, Ono, Taiho, Sanofi, Bristol- 
      Myers Squibb, and Bayer; and research funding from Parexel International, Merck 
      Serono, Daiichi-Sankyo, Sumitomo-Dainippon Pharma, Shionogi, Pfizer, Mediscience 
      Planning, and Solasia Pharma. HB has received honoraria from Taiho and Chugai; 
      and research funding from Taiho, Chugai and Yakult Honsha. KY has received 
      honoraria from Ono, Taiho, Chugai, Bayer, Bristol-Myers Squibb, and Eli Lilly; 
      and research funding from Quintiles MS, NanoCarrier, Eli Lilly, Sumitomo- 
      Dainippon Pharma, Takeda, Taiho, Chugai, MSD, Daiichi-Sankyo, and Ono. TS 
      receives a department support grant from Chugai and Yakult Honsha; honoraria from 
      Taiho and Chugai. MG has received honoraria from Taiho and Chugai. HM has 
      received research funding from Chugai. YS has received honoraria from Yakult 
      Honsha and Taiho. SM has received honoraria from Taiho. NT and TH were employees 
      of Taiho. The other authors declare that they have no conflicts of interest.
EDAT- 2020/12/18 06:00
MHDA- 2020/12/18 06:01
PMCR- 2020/08/31
CRDT- 2020/12/17 05:55
PHST- 2020/05/22 00:00 [received]
PHST- 2020/08/06 00:00 [revised]
PHST- 2020/08/18 00:00 [accepted]
PHST- 2020/12/17 05:55 [entrez]
PHST- 2020/12/18 06:00 [pubmed]
PHST- 2020/12/18 06:01 [medline]
PHST- 2020/08/31 00:00 [pmc-release]
AID - 10.35772/ghm.2020.01050 [doi]
PST - ppublish
SO  - Glob Health Med. 2020 Aug 31;2(4):240-246. doi: 10.35772/ghm.2020.01050.