A retrospective review of 30 patients with metastatic RCC who switched from the 4/2 schedule to a 2/1 schedule showed there were no grade 4 toxicities and fewer than 30% of patients experienced grade 3 toxicities.2

In this study, researchers found that 73% of patients reported that their worst toxicity was less severe on the 2/1 schedule compared to the 4/2 schedule.

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Dr. Rini and his colleagues say prospective data are warranted to ascertain the optimal schedule and phase II trials are now underway. It is theorized a 2/1 schedule could result in a lower rate of grade 3 toxicities, and permit a larger percentage of patients to remain on full-dose sunitinib.

“We were interested in improving the quality of life in patients with RCC who were receiving sunitinib therapy. We observed that toxicity worsened in the third and fourth weeks and hypothesized that patients would feel better and possibly enjoy similar efficacy if we instead administered the drug on a 2/1 schedule. Our retrospective observations support our hypothesis, and patients who switched to a 2/1 schedule experienced fewer toxicities while remaining on therapy,” said study co-investigator Eric Jonash, MD, who is an associate professor of genitourinary medical oncology at the University of Texas MD Anderson Cancer Center in Houston, TX.

Dr. Jonash said it is critical to work with patients earlier rather than later in the course of their treatment to address the issue of toxicity related to sunitinib use.

“Managing these toxicities by giving treatment breaks before reducing overall dose allows patients to optimize overall dose intensity without appreciably harming efficacy,” he told Cancer Therapy Advisor.

Saby George, MD, an assistant professor of oncology at Roswell Park Cancer Institute in Buffalo, NY, said the vast majority of patients tolerate the regular 4/2 schedule.

The alternate schedule is only applicable to the patients who do not tolerate the recommended dosing schedule. The variation is a function of individual patients’ ability to metabolize sunitinib.

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“I personally do not think a trial is needed to figure this out. Optimal sunitinib dose is the recommended dosing and if the dose needs to be reduced for safety for an individual patient, that is the right thing to do for that particular patient. If they tolerate the standard dose with maximal benefit, that would be right for them,” Dr. George told Cancer Therapy Advisor.

“There is no lack of data to support treatment with sunitinib. Indeed there is level I evidence for use of sunitinib in stage IV RCC. If sunitinib is intolerable, there are other tolerable TKIs available for use in advanced RCC. It is still a disappointing time for RCC patients as there is still no cure in cases of stage IV RCC. None of the treatments can cure RCC to date.”


  1. Kalra S, Rini BI, Jonasch E. Alternate sunitinib schedules in patients with metastatic renal cell carcinoma. Ann Oncol. January 26, 2015.  [Epub ahead of print] pii: mdv030.
  2. Najjar YG, Mittal K, Elson P, et al. A 2 weeks on and 1 week off schedule of sunitinib is associated with decreased toxicity in metastatic renal cell carcinoma. Eur J Cancer. 2014;50(6):1084-1089.