PMID- 35729008
OWN - NLM
STAT- MEDLINE
DCOM- 20230623
LR  - 20230623
IS  - 1958-5578 (Electronic)
IS  - 0040-5957 (Linking)
VI  - 78
IP  - 3
DP  - 2023 May-Jun
TI  - Pulmonary toxicity of mTOR inhibitors. Comparisons of two populations: Solid 
      organ recipients and cancer patients.
PG  - 267-278
LID - S0040-5957(22)00105-6 [pii]
LID - 10.1016/j.therap.2022.05.008 [doi]
AB  - INTRODUCTION: Mammalian target of rapamycin (mTOR) inhibitors-associated 
      pneumonitis (mTOR-IP) has long been described in solid organ recipients (T) 
      patients but more recently in cancer (K) patients. Its overall characteristics 
      have never been compared between these 2 populations. The aim of this study was 
      to compare them in terms of presentation, severity and outcome in T and in K 
      patients. MATERIAL AND METHODS: We carried out a retrospective study in a single 
      French tertiary center. Four databases were used to ensure the exhaustive 
      collection of all mTOR-IP cases between 2001 and 2020. All clinical, biological, 
      radiological, pathological and outcome data were reviewed. RESULTS: Thirty-nine 
      patients with mTOR-IP were diagnosed during this period, 24T and 15K patients. 
      The average dosage of everolimus and sirolimus was 2,65mg (+/-1,78) and 2,75mg 
      (+/-0,96) in T patients, respectively, versus 8,75mg (+/-2,26) for everolimus in K 
      patients. The overall prevalence of mTOR-IP was 6.4% with a median time of 
      occurrence of 7 months [IQR 3-35 months]. mTOR-IP were significantly more 
      frequent (P<0.001) and occurred earlier (P<0.001) in cancer patients. No 
      clinical, functional, radiological, pathological nor outcome differences were 
      otherwise observed between the 2 groups. Average everolimus blood levels at the 
      time of mTOR-IP diagnosis were in the range of recommended therapeutic values. 
      CONCLUSION: Our study shows that mTOR-IP is comparable in terms of presentation 
      in T and in K patients but that it occurs significantly earlier after drug 
      introduction in the latter. This raises questions as to the potential role of the 
      higher doses used in K patients as well as that of co-treatments in the pathogeny 
      of the disease.
CI  - Copyright (c) 2022 Societe francaise de pharmacologie et de therapeutique. 
      Published by Elsevier Masson SAS. All rights reserved.
FAU - Gendarme, Sebastien
AU  - Gendarme S
AD  - Service de pneumologie, centre de competence maladies pulmonaires rares, hopital 
      europeen Georges-Pompidou, AP-HP, 75000 Paris, France. Electronic address: 
      s-ge@hotmail.fr.
FAU - Pastre, Jean
AU  - Pastre J
AD  - Service de pneumologie, centre de competence maladies pulmonaires rares, hopital 
      europeen Georges-Pompidou, AP-HP, 75000 Paris, France.
FAU - Billaud, Eliane M
AU  - Billaud EM
AD  - Service de pharmacologie, hopital europeen Georges-Pompidou, AP-HP, 75000 Paris, 
      France.
FAU - Gibault, Laure
AU  - Gibault L
AD  - Service d'anatomopathologie et cytologie, hopital europeen Georges-Pompidou, 
      AP-HP, 75000 Paris, France.
FAU - Guillemain, Romain
AU  - Guillemain R
AD  - Unite de transplantation cardiaque et pulmonaire, hopital europeen 
      Georges-Pompidou, AP-HP, 75000 Paris, France.
FAU - Oudard, Stephane
AU  - Oudard S
AD  - Service d'oncologie medicale, hopital europeen Georges-Pompidou, AP-HP, 75000 
      Paris, France; Universite de Paris, 75000 Paris, France.
FAU - Medioni, Jacques
AU  - Medioni J
AD  - Service d'oncologie medicale, hopital europeen Georges-Pompidou, AP-HP, 75000 
      Paris, France; Universite de Paris, 75000 Paris, France.
FAU - Lillo-Lelouet, Agnes
AU  - Lillo-Lelouet A
AD  - Centre de pharmacovigilance, hopital europeen Georges-Pompidou, AP-HP, 75000 
      Paris, France.
FAU - Israel-Biet, Dominique
AU  - Israel-Biet D
AD  - Service de pneumologie, centre de competence maladies pulmonaires rares, hopital 
      europeen Georges-Pompidou, AP-HP, 75000 Paris, France; Universite de Paris, 75000 
      Paris, France.
LA  - eng
PT  - Journal Article
DEP - 20220608
PL  - France
TA  - Therapie
JT  - Therapie
JID - 0420544
RN  - 9HW64Q8G6G (Everolimus)
RN  - 0 (Immunosuppressive Agents)
RN  - 0 (MTOR Inhibitors)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - W36ZG6FT64 (Sirolimus)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Humans
MH  - Everolimus/adverse effects
MH  - Immunosuppressive Agents/adverse effects
MH  - *MTOR Inhibitors/adverse effects
MH  - *Neoplasms/drug therapy
MH  - Retrospective Studies
MH  - *Sirolimus/adverse effects
MH  - TOR Serine-Threonine Kinases/therapeutic use
OTO - NOTNLM
OT  - Adverse drug reactions
OT  - Everolimus
OT  - Interstitial lung disease
OT  - Sirolimus
OT  - TOR serine-threonine kinases
EDAT- 2022/06/22 06:00
MHDA- 2023/05/22 06:42
CRDT- 2022/06/21 22:04
PHST- 2021/12/31 00:00 [received]
PHST- 2022/04/14 00:00 [revised]
PHST- 2022/05/24 00:00 [accepted]
PHST- 2023/05/22 06:42 [medline]
PHST- 2022/06/22 06:00 [pubmed]
PHST- 2022/06/21 22:04 [entrez]
AID - S0040-5957(22)00105-6 [pii]
AID - 10.1016/j.therap.2022.05.008 [doi]
PST - ppublish
SO  - Therapie. 2023 May-Jun;78(3):267-278. doi: 10.1016/j.therap.2022.05.008. Epub 
      2022 Jun 8.