Most oral agents for renal cell carcinoma (RCC) are currently given in a continuous schedule. However, some studies have suggested that an alternate dosing and scheduling for sunitinib may provide advantages.
Now, researchers report that understanding just what the optimal dosing regimens may be for RCC could lead to improvements in the ability to refine dosing and scheduling for all oral anticancer therapies.1
“There are alternative ways of giving sunitinib that may allow for maintenance of dose, which in other studies has been shown to be associated with better clinical outcomes. It may allow the drug to be better tolerated. Given that sunitinib is noncurative, any alternatives to allow better tolerance for patients are an advance,” said study investigator Brian Rini, MD, who is an associate professor of medicine at the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University in Cleveland, OH.
Sunitinib malate, an oral multitargeted tyrosine kinase inhibitor, has been shown to improve outcomes in comparison to interferon alpha (IFN-α) and studies have confirmed that patients with RCC have better outcomes with higher exposure to sunitinib.
However, maintenance of sunitinib dose intensity can be challenging due to well documented treatment-related adverse events (AEs) such as fatigue, hypertension, hand–foot syndrome, and diarrhea.
It is often noted that treatment-AEs increase throughout each cycle, and tend to be worst in the final 2 weeks of the treatment cycle.
Dr. Rini and his colleagues conducted a literature search in the Medline database using terms renal cell carcinoma, RCC, sunitinib, pharmacokinetics, pharmacodynamics, and endothelial cells between January 2000 and June 2014.
The Medline search also included published abstracts from the American Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO).
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The investigators concluded that there is no conclusive evidence suggesting optimal dosing and scheduling of sunitinib. The researchers found that a sunitinib steady state is reached as well as optimal suppression of vascular perfusion after 2 weeks of therapy.
Various alternative interrupted therapies have been evaluated but only in the retrospective setting. Patients who were either started on or switched to alternate schedules during their course of treatment appeared to maintain clinical efficacy.
Some clinicians have tried giving lower daily doses and some successful strategies have employed the 4-week on followed by 2-week off (4/2) schedule and 2 weeks on, 1 week off (2/1) schedule.