TY - JOUR
T1 - Natural history, management and pharmacokinetics of Everolimus-induced-oral ulcers
T2 - Insights into compliance issues
AU - Ferté, Charles
AU - Paci, Angelo
AU - Zizi, Meriem
AU - Gonzales, Daniel Barrios
AU - Goubar, Aicha
AU - Gomez-Roca, Carlos
AU - Massard, Christophe
AU - Sahmoud, Tarek
AU - André, Fabrice
AU - Soria, Jean Charles
PY - 2011/10/1
Y1 - 2011/10/1
N2 - Background: Oral Ulcers is a well-recognised adverse event (AE) of mTOR inhibitors. Paradoxically, little is known about its natural history, risk factors, and basic management. Patients and methods: AEs of 79 patients prospectively enrolled in 6 phase I-II studies testing Everolimus were reviewed. The following parameters were analysed: incidence, severity, duration and associated AE. The association between OU and Everolimus dose, pharmacokinetics and the effectiveness of empiric treatments were explored. Results: OU, grade 3-4 OU, prolonged time under OU and RCOU (recurrent and chronic oral ulcer) were observed in 72% 11%, 30% and 25% patients, respectively. Patients with antecedent of prior chemotherapy, with PS 1, or receiving Everolimus in combination tended to present higher rates of prolonged time under OU and of grade 3-4 OU. As Everolimus daily dose increased, the median time to OU was shorter, the median duration was longer and OU incidence tended to increase. Simultaneously, OU tended to be associated with higher Everolimus exposure. None of the empiric treatments appeared effective against OU (preventive or curative intent). Conclusion: Everolimus-induced OU is a frequent, recurrent and sometimes harmful complication. A dose effect relationship is displayed. Its daily management remains challenging. OU represents a key issue in the compliance of mTOR inhibitors.
AB - Background: Oral Ulcers is a well-recognised adverse event (AE) of mTOR inhibitors. Paradoxically, little is known about its natural history, risk factors, and basic management. Patients and methods: AEs of 79 patients prospectively enrolled in 6 phase I-II studies testing Everolimus were reviewed. The following parameters were analysed: incidence, severity, duration and associated AE. The association between OU and Everolimus dose, pharmacokinetics and the effectiveness of empiric treatments were explored. Results: OU, grade 3-4 OU, prolonged time under OU and RCOU (recurrent and chronic oral ulcer) were observed in 72% 11%, 30% and 25% patients, respectively. Patients with antecedent of prior chemotherapy, with PS 1, or receiving Everolimus in combination tended to present higher rates of prolonged time under OU and of grade 3-4 OU. As Everolimus daily dose increased, the median time to OU was shorter, the median duration was longer and OU incidence tended to increase. Simultaneously, OU tended to be associated with higher Everolimus exposure. None of the empiric treatments appeared effective against OU (preventive or curative intent). Conclusion: Everolimus-induced OU is a frequent, recurrent and sometimes harmful complication. A dose effect relationship is displayed. Its daily management remains challenging. OU represents a key issue in the compliance of mTOR inhibitors.
KW - Everolimus
KW - Management
KW - Mucositis
KW - Oral ulcer
KW - mTOR inhibitors
UR - http://www.scopus.com/inward/record.url?scp=80053377953&partnerID=8YFLogxK
U2 - 10.1016/j.ejca.2011.03.017
DO - 10.1016/j.ejca.2011.03.017
M3 - Article
C2 - 21489779
AN - SCOPUS:80053377953
SN - 0959-8049
VL - 47
SP - 2249
EP - 2255
JO - European Journal of Cancer
JF - European Journal of Cancer
IS - 15
ER -