Correlating Renal Cell Cancer Treatment Efficacy With Sunitinib Therapeutic Levels and Outcomes
Rationale: Sunitinib is an oral multi-targeted tyrosine kinase inhibitor used for first-line
systemic therapy in metastatic renal cell carcinoma. It is metabolised to a
pharmacologically active metabolite, SU012662, which is of equal potency to the parent
compound. At a standard 50mg daily dose, variability in plasma levels between patients is
approximately ten-fold. In clinical trials, over 30% of patients require a dose reduction
due to toxicity. However, some patients can tolerate up to 100mg without excessive toxicity.
It is unknown if sunitinib clearance changes with time. Pre-clinical experiments observed
tyrosine kinase inhibition at a plasma concentration of 50-100ng/ml.
Design: This is a prospective non-randomized, Phase II clinical study. Decision to treat
patients with single-agent sunitinib is pre-determined by treating specialists before
entering this study. Toxicity and trough sunitinib/metabolite levels will be measured every
six weeks during treatment.
Aim: This study will prospectively examine the relationship between steady-state trough
levels of sunitinib/metabolites and the time on treatment, in addition to changes in trough
levels over time. Trough levels will also be correlated with other measures of efficacy and
treatment-related toxicity. Furthermore, we aim to confirm that the putative target of
50ng/ml correlates with toxicity and time on sunitinib.
Observational Model: Cohort, Time Perspective: Prospective
Time to treatment failure (time on sunitinib treatment)
This duration extends from the date the patient starts sunitinib until the date sunitinib is abandoned. The group with sunitinib concentration below the population median are expected to have a median Time to Treatment Failure (TTF) of approximately 8 months, compared with 14 months in those with sunitinib concentration above the population median.
Sunitinib duration (median)
Howard Gurney, MBBS, FRACP
Crown Princess Mary Cancer Centre, Westmead
Australia: Human Research Ethics Committee