TY - JOUR
T1 - Predictive factors of renal toxicities related to anti-VEGFR multikinase inhibitors in phase 1 trials
AU - Boissier, Emilie
AU - Mir, Olivier
AU - Hollebecque, Antoine
AU - Izzedine, Hassan
AU - Ederhy, Stéphane
AU - Gazzah, Anas
AU - Bahleda, Rastislav
AU - Massard, Christophe
AU - Macquin-Mavier, Isabelle
AU - Tournigand, Christophe
AU - Spano, Jean Philippe
AU - Soria, Jean Charles
AU - Rousseau, Benoît
N1 - Publisher Copyright:
© 2016, Springer Science+Business Media New York.
PY - 2017/2/1
Y1 - 2017/2/1
N2 - Purpose Renal toxicities are common with angiogenesis multikinase inhibitors (AMKI), and can be limiting in phase I trials. Factors associated with such toxicities are poorly known. The aims of this exploratory study were to describe renovascular toxicities associated with AMKI, impact on drug development and to identify baseline parameters associated with the occurrence of renal toxicities in phase I trials. Methods Consecutive patients treated with AMKI in Gustave Roussy phase I unit between October 2005 and August 2013 were included. We retrospectively collected baseline characteristics and renovascular side effects. Associations were assessed in univariate and multivariate analyses. Results Overall, 168 patients were included: male 53.0 %, mean age 55.5 years old, history of hypertension 26.8 %, diabetes 6.0 %, atherosclerosis 13.6 %, stage 3 Chronic Kidney Disease (CKD, NKF-KDOQI) 17.2 %. Incidences of reno-vascular side effects were: hypertension 47.6 %, proteinuria 19.0 %, renal failure 11.9 % and thrombotic microangiopathy 10.1 %. Eighty percent of dose limiting toxicities (DLTs) were related to a renal toxicity. Multivariate analysis showed that onset of renal failure was associated with history of hypertension (p = 0.0003) and stage 3 CKD (p = 0.032). Conclusions A majority of the DLTs associated with AMKI in phase 1 trials are renal toxicities. Baseline hypertension and stage 3 CKD (NKF-KDOQI) might help to better identify patients at risk of AMKI-related renal toxicities.
AB - Purpose Renal toxicities are common with angiogenesis multikinase inhibitors (AMKI), and can be limiting in phase I trials. Factors associated with such toxicities are poorly known. The aims of this exploratory study were to describe renovascular toxicities associated with AMKI, impact on drug development and to identify baseline parameters associated with the occurrence of renal toxicities in phase I trials. Methods Consecutive patients treated with AMKI in Gustave Roussy phase I unit between October 2005 and August 2013 were included. We retrospectively collected baseline characteristics and renovascular side effects. Associations were assessed in univariate and multivariate analyses. Results Overall, 168 patients were included: male 53.0 %, mean age 55.5 years old, history of hypertension 26.8 %, diabetes 6.0 %, atherosclerosis 13.6 %, stage 3 Chronic Kidney Disease (CKD, NKF-KDOQI) 17.2 %. Incidences of reno-vascular side effects were: hypertension 47.6 %, proteinuria 19.0 %, renal failure 11.9 % and thrombotic microangiopathy 10.1 %. Eighty percent of dose limiting toxicities (DLTs) were related to a renal toxicity. Multivariate analysis showed that onset of renal failure was associated with history of hypertension (p = 0.0003) and stage 3 CKD (p = 0.032). Conclusions A majority of the DLTs associated with AMKI in phase 1 trials are renal toxicities. Baseline hypertension and stage 3 CKD (NKF-KDOQI) might help to better identify patients at risk of AMKI-related renal toxicities.
KW - Antiangiogenic agents
KW - Cancer
KW - Drug safety
KW - Renal failure
UR - http://www.scopus.com/inward/record.url?scp=84992428909&partnerID=8YFLogxK
U2 - 10.1007/s10637-016-0402-3
DO - 10.1007/s10637-016-0402-3
M3 - Article
C2 - 27783256
AN - SCOPUS:84992428909
SN - 0167-6997
VL - 35
SP - 79
EP - 86
JO - Investigational New Drugs
JF - Investigational New Drugs
IS - 1
ER -