PMID- 28761740
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210126
IS  - 2059-7029 (Print)
IS  - 2059-7029 (Electronic)
IS  - 2059-7029 (Linking)
VI  - 2
IP  - 2
DP  - 2017
TI  - Patient-reported tolerability of adverse events in phase 1 trials.
PG  - e000148
LID - 10.1136/esmoopen-2016-000148 [doi]
LID - e000148
AB  - BACKGROUND: Phase I experts recommend revisiting dose-limiting toxicity (DLT) 
      definition to include chronic and cumulative toxicities induced by new 
      molecularly targeted therapies. Patient's assessment of late toxicities' 
      tolerability is, however, unknown. MATERIALS AND METHODS: A prospective survey on 
      adverse events (AEs) tolerability on 23 National Cancer InstituteCommon 
      Terminology Criteria for Adverse Event, Version 4 (NCI-CTCAE.v4) items was 
      conducted at Gustave Roussy's Phase I department. Patients' maximum tolerability 
      duration was recorded at baseline, during trial and at trial completion. Results 
      were compared with the corresponding physicians' survey. RESULTS: 52 patients 
      enrolled in 27 Phase I trials between May 2014 and November 2015 completed 102 
      forms. At baseline, the most feared G2/G3 AEs were haematuria (74%), vomiting 
      (71%) and hyperglycemia (64%)/dry mouth (94%), hyperglycemia (92%) and vomiting 
      (92%). At trial completion, the most feared G2/G3 AEs were personality change 
      (83.3%), haematuria (82%) and fever (80%)/dry mouth, fever and dizziness (100% 
      each). Tolerability score did not differ over time. More previous treatments and 
      occurrence of severe AEs were associated with better tolerability at study 
      completion (p=0.0234 and p=0.0153, respectively, in multivariate analysis). 
      Patient's tolerability differed from physician's assessment. CONCLUSION: AEs 
      considered intolerable by patients are toxicities that directly impact their 
      quality of life and differ from those feared by physicians or included in DLT 
      definition. Patient-reported tolerability of AEs may help in optimising drug 
      development.
FAU - Henon, Clemence
AU  - Henon C
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
FAU - Lissa, Delphine
AU  - Lissa D
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
FAU - Paoletti, Xavier
AU  - Paoletti X
AD  - Biostatistics and Epidemiology Department, Gustave Roussy Cancer Campus, 
      Villejuif, France.
AD  - CESP-OncoStat, INSERM and Paris-Saclay University, Paris-Sud University, 
      Versailles Saint-Quentin-en-Yvelines University, Villejuif, France.
FAU - Thibault, Constance
AU  - Thibault C
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
FAU - Le Tourneau, Christophe
AU  - Le Tourneau C
AD  - Department of Medical Oncology, Institut Curie, Paris, France.
AD  - UMR900, INSERM, Paris, France.
FAU - Lanoy, Emilie
AU  - Lanoy E
AD  - Biostatistics and Epidemiology Department, Gustave Roussy Cancer Campus, 
      Villejuif, France.
AD  - CESP-OncoStat, INSERM and Paris-Saclay University, Paris-Sud University, 
      Versailles Saint-Quentin-en-Yvelines University, Villejuif, France.
FAU - Hollebecque, Antoine
AU  - Hollebecque A
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
FAU - Massard, Christophe
AU  - Massard C
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
FAU - Soria, Jean-Charles
AU  - Soria JC
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
AD  - UMR981, INSERM, Villejuif, France.
FAU - Postel-Vinay, Sophie
AU  - Postel-Vinay S
AD  - Drug Development department (DITEP), Gustave Roussy Cancer Campus, Paris-Saclay 
      University, Villejuif, France.
AD  - UMR981, INSERM, Villejuif, France.
LA  - eng
PT  - Journal Article
DEP - 20170623
PL  - England
TA  - ESMO Open
JT  - ESMO open
JID - 101690685
PMC - PMC5519806
OTO - NOTNLM
OT  - Dose limiting toxicity
OT  - adverse event
OT  - patient reported outcome
OT  - phase 1
OT  - tolerability
COIS- Competing interests: None declared.
EDAT- 2017/08/02 06:00
MHDA- 2017/08/02 06:01
PMCR- 2017/06/23
CRDT- 2017/08/02 06:00
PHST- 2016/12/13 00:00 [received]
PHST- 2017/02/12 00:00 [revised]
PHST- 2017/02/15 00:00 [accepted]
PHST- 2017/08/02 06:00 [entrez]
PHST- 2017/08/02 06:00 [pubmed]
PHST- 2017/08/02 06:01 [medline]
PHST- 2017/06/23 00:00 [pmc-release]
AID - S2059-7029(20)32445-5 [pii]
AID - esmoopen-2016-000148 [pii]
AID - 10.1136/esmoopen-2016-000148 [doi]
PST - epublish
SO  - ESMO Open. 2017 Jun 23;2(2):e000148. doi: 10.1136/esmoopen-2016-000148. 
      eCollection 2017.