Alternative Dosing Schedules for Targeted Agents in RCC

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Although sunitinib has been used in the treatment of renal cell carcinoma (RCC) for the last 10 years, clinicians are only recently exploring different dosing schedules for patients, Brian I. Rini, MD, notes. Utilizing a dosing schedule of 2 weeks on therapy followed by 1 week off, for example, rather than the traditional dosing schedule of 4 weeks on therapy followed by 2 weeks off, has resulted in improved tolerability for some patients. Rini comments that, in general, many RCC patients are not going to achieve complete response with these agents, and in these cases, he administers only enough medication to control disease.

In the COMPARZ trial, which evaluated the use of sunitinib and pazopanib in patients with metastatic RCC, participants received sunitinib once daily for 4 weeks followed by 2 weeks without treatment, notes Rini. At this year’s annual meeting of the American Society of Clinical Oncology, researchers presented the results of studies in which patients took longer treatment-free periods, or breaks, than in COMPARZ. The median initial length of break was 16 months in these studies.

Charles A. Henderson, MD, states that he has treated several patients who have taken prolonged breaks, and adds that he has had patients who have mentioned to him that they needed a break. Janice P. Dutcher, MD, describes her experience with alternative dosing schedules, and notes that she has seen control of brain metastases in patients receiving low-dose sunitinib that was not given daily. She notes that some patients are on schedules that involve 5 days on sunitinib followed by 2 days off because they do not want to discontinue therapy, but need a break.

Henderson has seen patients who were apprehensive about taking a break for fear of experiencing disease progression after stopping the medication. He describes a patient with lung metastases who went into complete remission on sunitinib and does not want to discontinue therapy.

Clinicians should be especially mindful of RCC patients with disease that affects “dangerous” sites, such as the brain and bone, remarks Rini. Although these individuals can take breaks from treatment, says Rini, his threshold to reinitiate treatment is lower. He instructs these patients to contact him at the first sign of trouble, such as pain.