PMID- 35799138
OWN - NLM
STAT- MEDLINE
DCOM- 20220711
LR  - 20220716
IS  - 1471-2407 (Electronic)
IS  - 1471-2407 (Linking)
VI  - 22
IP  - 1
DP  - 2022 Jul 7
TI  - Efficacy of donepezil for the treatment of oxaliplatin-induced peripheral 
      neuropathy: DONEPEZOX, a protocol of a proof of concept, randomised, 
      triple-blinded and multicentre trial.
PG  - 742
LID - 10.1186/s12885-022-09806-8 [doi]
LID - 742
AB  - BACKGROUND: The use of oxaliplatin in digestive tract cancers could induce severe 
      peripheral neuropathy (OIPN) decreasing the quality of life of patients and 
      survivors. There is currently, no univocal treatment for these peripheral 
      neuropathies. Donepezil, a reversible inhibitor of cholinesterase, used to treat 
      Alzheimer's disease and dementia, is reported to have a good safety profile in 
      humans, and preclinical data have provided initial evidence of its effectiveness 
      in diminishing neuropathic symptoms and related comorbidities in OIPN animal 
      models. METHODS: The DONEPEZOX trial will be a proof-of-concept, randomised, 
      triple-blinded, and multicentre study. It will be the first clinical trial 
      evaluating the efficacy and safety of donepezil for the management of OIPN. Adult 
      cancer survivors with OIPN that report sensory neuropathy according to QLQ-CIPN20 
      sensory score (equivalence of a grade >/= 2), at least 6 months after the end of an 
      oxaliplatin-based chemotherapy will be included. Eighty patients will be randomly 
      assigned to receive either donepezil or placebo over 16 weeks of treatment. The 
      primary endpoint will be the rate of responders (neuropathic grade decreases 
      according to the QLQ-CIPN20 sensory score) in the donepezil arm. The severity of 
      OIPN will be assessed by the QLQ-CIPN20 sensory scale before and after 16 weeks 
      of treatment. The comparison versus the placebo arm will be a secondary 
      objective. The other secondary endpoints will be tolerance to donepezil, the 
      severity and features of OIPN in each arm before and after treatment, 
      related-comorbidities and quality of life. Fleming's one-stage design will be 
      used for sample size estimation. This design yields a type I error rate of 0.0417 
      and power of 91% for a responder rate of at least 30% in donepezil arm. A total 
      of 80 randomized patients is planned. DISCUSSION: This study will allow, in the 
      case of positive results, to initiate a phase 3 randomized and placebo-controlled 
      (primary endpoint) clinical study to assess the therapeutic interest of donepezil 
      to treat OIPN. TRIAL REGISTRATION: NCT05254639 , clincialtrials.gov, Registered 
      24 February 2022.
CI  - (c) 2022. The Author(s).
FAU - Kerckhove, Nicolas
AU  - Kerckhove N
AUID- ORCID: 0000-0003-2223-1240
AD  - UMR 1107 NEURODOL, service de pharmacologie medicale, CHU Clermont-Ferrand, 
      Universite Clermont Auvergne, INSERM, 63000, Clermont-Ferrand, France. 
      nkerckhove@chu-clermontferrand.fr.
FAU - Tougeron, David
AU  - Tougeron D
AD  - Service d'Hepato gastroenterologie, CHU Poitiers, 86000, Poitiers, France.
FAU - Lepage, Come
AU  - Lepage C
AD  - Service d'Hepatogastroenterologie et oncologie digestive, CHU Dijon, Universite 
      de Bourgogne, Dijon, France.
AD  - UMR LNC 1231, EPICAD INSERM, Universite de Bourgogne, Dijon, France.
FAU - Pezet, Denis
AU  - Pezet D
AD  - Service de chirurgie digestive, U1071, M2iSH, USC-INRA 2018, CHU 
      Clermont-Ferrand, Universite Clermont Auvergne, INSERM, INRA, 63000, 
      Clermont-Ferrand, France.
FAU - Le Malicot, Karine
AU  - Le Malicot K
AD  - UMR LNC 1231, EPICAD INSERM, Universite de Bourgogne, Dijon, France.
AD  - Federation Francophone de Cancerologie Digestive (FFCD), 21079, Dijon, France.
FAU - Pelkowski, Manon
AU  - Pelkowski M
AD  - UMR LNC 1231, EPICAD INSERM, Universite de Bourgogne, Dijon, France.
AD  - Federation Francophone de Cancerologie Digestive (FFCD), 21079, Dijon, France.
FAU - Pereira, Bruno
AU  - Pereira B
AD  - Direction de la recherche clinique et de l'innovation, CHU Clermont-Ferrand, 
      63000, Clermont-Ferrand, France.
FAU - Balayssac, David
AU  - Balayssac D
AD  - UMR 1107 NEURODOL, service de pharmacologie medicale, CHU Clermont-Ferrand, 
      Universite Clermont Auvergne, INSERM, 63000, Clermont-Ferrand, France.
AD  - Direction de la recherche clinique et de l'innovation, CHU Clermont-Ferrand, 
      63000, Clermont-Ferrand, France.
LA  - eng
SI  - ClinicalTrials.gov/NCT05254639
GR  - 20-082 PHRC-K 2020/Institut National Du Cancer/
PT  - Clinical Trial Protocol
PT  - Journal Article
DEP - 20220707
PL  - England
TA  - BMC Cancer
JT  - BMC cancer
JID - 100967800
RN  - 04ZR38536J (Oxaliplatin)
RN  - 8SSC91326P (Donepezil)
SB  - IM
MH  - Clinical Trials, Phase III as Topic
MH  - Donepezil/therapeutic use
MH  - Humans
MH  - Multicenter Studies as Topic
MH  - Oxaliplatin/adverse effects
MH  - *Peripheral Nervous System Diseases/chemically induced/drug therapy
MH  - Quality of Life
MH  - Randomized Controlled Trials as Topic
PMC - PMC9264497
OTO - NOTNLM
OT  - Anticholinesterase
OT  - Chemotherapy-induced peripheral neuropathy
OT  - Donepezil
OT  - Oxaliplatin
OT  - Pain
OT  - Study protocol
COIS- The authors declare that they have no competing interests. MYLAN will not provide 
      donepezil free of charge and will not participate in any stage of the clinical 
      study or analysis of the results.
EDAT- 2022/07/08 06:00
MHDA- 2022/07/12 06:00
PMCR- 2022/07/07
CRDT- 2022/07/07 23:44
PHST- 2022/05/09 00:00 [received]
PHST- 2022/06/22 00:00 [accepted]
PHST- 2022/07/07 23:44 [entrez]
PHST- 2022/07/08 06:00 [pubmed]
PHST- 2022/07/12 06:00 [medline]
PHST- 2022/07/07 00:00 [pmc-release]
AID - 10.1186/s12885-022-09806-8 [pii]
AID - 9806 [pii]
AID - 10.1186/s12885-022-09806-8 [doi]
PST - epublish
SO  - BMC Cancer. 2022 Jul 7;22(1):742. doi: 10.1186/s12885-022-09806-8.