Over the last 8 years, targeted therapy has revolutionized the treatment of metastatic renal cell carcinoma (mRCC).  The U.S. Food and Drug Administration (FDA) has approved seven medications for the treatment of RCC since 2005, and other promising agents are on the horizon.  However, clinicians are faced with significant treatment-related and patient-related barriers.

In the current era, drug toxicity and resistance are major barriers to optimizing the use of many new targeted therapies; therefore optimal treatment selection, patient education, and proactive management of these drug toxicities may be the keys to improving survival rates among patients with mRCC, according to researchers at the Cleveland Clinic.  Kriti Mittal, MD, and Brian Rini, MD, of the Cleveland Clinic Taussig Cancer Institute, Cleveland, OH presented an overview on maintaining dose intensity and best supportive care of patients with mRCC at the 2013 Genitourinary Cancers Symposium, held February 14-16 in Orlando, FL.  The presentation highlighted the fact that clinicians now have several new effective agents, but are still challenged with preserving quality of life and improving clinical outcomes.

It is well established that effective drug dosing needs to be individualized to each patient.  In addition, Dr. Rini notes, it may be best to consider giving some patients higher doses intermittently instead of reduced-intensity continuous dosing. “I think there is a role for intermittent therapy, but this is still investigational.  Cleveland Clinic and others are investigating alternative ways to give these chronic therapies to preserve benefit and reduce toxicity,” said Dr. Rini, Associate Professor of Medicine at the Cleveland Clinic, Cleveland, OH.

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Clinicians treating patients with mRCC may want to consider delaying the start of systemic therapy or allowing extended breaks from therapy as a way of minimizing treatment-related morbidity while improving overall survival (OS), Dr. Rini said.  During the symposium, researchers reported that treatment with sunitinib with a 2-weeks-on and 1-week-off schedule may be associated with significantly decreased toxicity in patients who initially have grade 3 or greater toxicity on the standard sunitinib schedule.1

The current standard dosing for sunitinib is 4 weeks of treatment followed by 2 weeks of rest (schedule 4/2).  However, at the Cleveland Clinic, several patients were switched to a 2/1 schedule (2 weeks on medication and one week off medication) after experiencing toxicity.  The 2/1 schedule was set up in an attempt to reduce drug-related toxicity while maintaining the routine daily dose. The researchers retrospectively reviewed the records of 21 patients, where 71% were male and 78% of patients had clear cell histology.  Among these 21 patients, 29% had prior systemic therapy for mRCC and all but one had prior nephrectomy.1

The study demonstrated that treatment with sunitinib on the 2/1 schedule was associated with significantly decreased toxicity and could considerably extend treatment duration.  In this group of patients, 95% of the patients had grade 3 or 4 toxicity on the 4/2 schedule, and for this reason, were switched to the 2/1 schedule.  The researchers found no grade 4 toxicities on the 2/1 schedule and only 33% of patients experienced grade 3 toxicity.