Feasibility of Therapeutic Drug Monitoring of Sunitinib and its
implications on response and toxicity in patients with metastatic renal
cell cancer
Abstract
High interindividual variability in pharmacokinetics coupled with
concentration-effect relationship make sunitinib an ideal candidate for
therapeutic drug monitoring (TDM). The feasibility of TDM of sunitinib
in patients with metastatic renal cell carcinoma (mRCC) was evaluated in
this prospective observational study. Seventy patients with mRCC treated
with sunitinib 50mg OD were enrolled. Total trough levels (TTL) of
sunitinib and N-desethyl sunitinib were measured between days 10-14 of
cycle 1. The discriminatory potential of TTL of sunitinib for the
prediction of responders and occurrence of grade ≥3 toxicity was
determined using receiver operating characteristic (ROC) curve.
Threshold concentrations obtained from ROC analysis showed that TTL
≥60.75ng/mL was associated with higher response rates and TTL ≥82.3ng/mL
was associated with higher incidence of grade ≥3 toxicity compared with
lower exposures (31/34 versus 5/12, P=0.001 and 9/24 versus 4/36;
P=0.024 respectively). More than 50% of patients in our cohort attained
TTL outside the optimal range of 60.75-82.3 ng/mL demonstrating the
feasibility of TDM.