PMID- 38063405
OWN - NLM
STAT- MEDLINE
DCOM- 20240101
LR  - 20240123
IS  - 2045-7634 (Electronic)
IS  - 2045-7634 (Linking)
VI  - 12
IP  - 24
DP  - 2023 Dec
TI  - Efficacy and safety of fruquintinib dose-escalation strategy for elderly patients 
      with refractory metastatic colorectal cancer: A single-arm, multicenter, phase II 
      study.
PG  - 22038-22046
LID - 10.1002/cam4.6786 [doi]
AB  - BACKGROUND: Fruquintinib has demonstrated significant improvement in overall 
      survival (OS) among previously treated metastatic colorectal cancer (mCRC) 
      patients. However, the utilization of fruquintinib has been constrained by 
      various toxicities, such as hand-foot skin reaction (HFSR) and hypertension, 
      particularly in elderly patients with reduced tolerance to the standard dosage. 
      This study aims to investigate the efficacy and safety of fruquintinib 
      dose-escalation strategy for elderly refractory mCRC patients. PATIENTS AND 
      METHODS: This open-label, single-arm, phase II trial included patients aged 
      65 years or over with mCRC who had progressed after two or more lines of 
      chemotherapy. Fruquintinib was administered for 21 consecutive days of a 28-day 
      treatment cycle. The starting dose of fruquintinib was 3 mg/day and escalated to 
      4 mg/day in Week 2 and 5 mg/day in Week 3 if no significant drug-related toxicity 
      was observed. The highest tolerated dose from Cycle 1 would be administered in 
      Cycle 2 and all subsequent cycles. Before commencing treatment, all enrolled 
      patients underwent a G8 questionnaire and comprehensive geriatric assessments. 
      The primary endpoint of the study was progression-free survival (PFS). RESULTS: A 
      total of 29 patients were enrolled and all started fruquintinib at 3 mg/day. 
      Fifteen patients (51.7%) were subsequently escalated to 4 mg/day and 4 (13.8%) to 
      5 mg/day. Only four (13.8%) patients discontinued treatment due to adverse events 
      (AEs). The median PFS was 3.8 months (95% CI, 2.7-4.9), and the median OS was 
      7.6 months (95% CI, 6.5-8.7). Treatment-related adverse events (TRAEs) were 
      observed in all 29 patients (100%). The most frequently occurring (>10%) TRAEs 
      greater than Grade 3 were HFSR (20.7%), hypertension (20.7%), and diarrhea 
      (10.3%). CONCLUSION: Our study indicated that a dose of 4 mg/day was well 
      tolerated by most elderly patients, suggesting that fruquintinib dose-escalation 
      strategy during the first cycle could serve as a viable alternative to the 
      standard 5 mg/day dosing.
CI  - (c) 2023 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.
FAU - Tan, Sirui
AU  - Tan S
AD  - Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan 
      University, Sichuan, China.
FAU - Zhang, Shunyu
AU  - Zhang S
AD  - Gastric Cancer Center, West China Hospital, Sichuan University, Sichuan, China.
FAU - Zhou, Nan
AU  - Zhou N
AD  - Gastric Cancer Center, West China Hospital, Sichuan University, Sichuan, China.
FAU - Cai, Xiaohong
AU  - Cai X
AD  - Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, 
      University of Electronic Science and Technology of China, Chengdu, China.
FAU - Yi, Cheng
AU  - Yi C
AUID- ORCID: 0000-0002-5963-5751
AD  - Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan 
      University, Sichuan, China.
FAU - Gou, Hongfeng
AU  - Gou H
AUID- ORCID: 0000-0002-2071-6773
AD  - Department of Medical Oncology, Cancer Center, West China Hospital, Sichuan 
      University, Sichuan, China.
AD  - Gastric Cancer Center, West China Hospital, Sichuan University, Sichuan, China.
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Journal Article
PT  - Multicenter Study
DEP - 20231208
PL  - United States
TA  - Cancer Med
JT  - Cancer medicine
JID - 101595310
RN  - 49DXG3M5ZW (HMPL-013)
RN  - 0 (Benzofurans)
SB  - IM
MH  - Aged
MH  - Humans
MH  - *Colorectal Neoplasms/pathology
MH  - *Colonic Neoplasms/drug therapy
MH  - *Benzofurans/adverse effects
MH  - *Rectal Neoplasms/drug therapy
MH  - *Hypertension/chemically induced
MH  - Antineoplastic Combined Chemotherapy Protocols/therapeutic use
PMC - PMC10757135
OTO - NOTNLM
OT  - dose-escalation
OT  - fruquintinib
OT  - geriatric assessment
OT  - mCRC
OT  - third-line therapy
COIS- The authors have no conflict of interest.
EDAT- 2023/12/08 12:42
MHDA- 2024/01/02 11:42
PMCR- 2023/12/08
CRDT- 2023/12/08 09:04
PHST- 2023/08/24 00:00 [revised]
PHST- 2023/07/03 00:00 [received]
PHST- 2023/09/30 00:00 [accepted]
PHST- 2024/01/02 11:42 [medline]
PHST- 2023/12/08 12:42 [pubmed]
PHST- 2023/12/08 09:04 [entrez]
PHST- 2023/12/08 00:00 [pmc-release]
AID - CAM46786 [pii]
AID - 10.1002/cam4.6786 [doi]
PST - ppublish
SO  - Cancer Med. 2023 Dec;12(24):22038-22046. doi: 10.1002/cam4.6786. Epub 2023 Dec 8.