Hemodialysis does not impact axitinib exposure: clinical case of a patient with metastatic renal cell carcinoma.

Axitinib is approved with indication in patients with advanced renal cell carcinoma (RCC). Due to the localization of this cancer, physicians sometimes have to deal with hemodialyzed patients. Data exploring hemodialysis (HD) impact on axitinib pharmacokinetic (PK) or safety are lacking. To date, no data have been published on that problematic. This is the first publication discussing the assessment of axitinib PK for a patient undergoing HD. Our results suggest that there is no influence of HD on axitinib blood concentration. Interestingly, the membranes used are common and represent around 90% of the membranes used in routine for HD. Our data are also reassuring both from activity and from safety perspectives. In that case, axitinib administered at a dose of 6 mg twice a day was well tolerated and allowed 12 months of disease control. These results are in line with previous publications discussing other anti-angiogenic tyrosine kinase inhibitors pharmacokinetics, safety and activity among patients with metastatic RCC undergoing hemodialysis.

Relative impact of ribavirin monitoring and HIV coinfection on sustained virological response in patients with chronic hepatitis C.

BACKGROUND: In chronic hepatitis C, higher ribavirin (RBV) concentrations are associated with sustained virological response (SVR); target concentration cutoffs have been proposed. As RBV displays interindividual variability, monitoring of RBV plasma levels appears relevant. The impact of RBV therapeutic drug monitoring (TDM(RBV)) on SVR has not been explored in current practice. Our study aimed to assess this impact. METHODS: Three patient groups were defined as RBV cutoffs achieved at week 12 (group A1), not achieved (group A2), and one without RBV concentration assessment (group B). A predictive model assessed the group impact on SVR in multivariate analysis, while adjusting for additional predictive factors. A specific evaluation of HIV-HCV-coinfected patients was performed. RESULTS: A total of 122 patients were included. In group A1 (n=30, HIV-positive =18), SVR, relapse and non-response rates were 60%, 17% and 23%, respectively; in group A2 (n=32, HIV-positive =18), 25%, 19% and 56%, respectively; and in group B (n=60, HIV-positive =3), 52%, 33% and 15%, respectively (P=0.0004). The patient group was an independent predictor of SVR (P=0.01), along with baseline viral load and HCV genotype. HIV coinfection did not impede the SVR rate. The cutoffs were achieved in 62% and 28% (P=0.008) of patients, when TDM(RBV) was performed or not, respectively. CONCLUSIONS: The achievement of RBV cutoffs is a predictive factor of SVR independent of HIV coinfection. It makes it possible to reach high SVR rates, avoid relapse and obtain the same SVR rates in HIV-HCV-coinfected as in HCV-monoinfected patients. TDM(RBV) enables RBV concentration cutoffs to be reached more frequently and could thus be a useful tool to optimize hepatitis C treatment.