ORLANDO—Oncology pharmacists can stick with the approved dosing for sunitinib in the treatment of advanced renal cell carcinoma (RCC), according to a study by New York investigators.
A dosing schedule of 50 mg daily for 4 weeks, followed by 2 weeks off treatment (4/2) of sunitinib appears to be the optimal dosing schedule as first-line treatment of advanced RCC. In a phase 2 study, researchers compared different dosing schedules of this vascular endothelial growth factor inhibitor and found that patients treated with a 37.5- mg continuous daily dose (CDD) regimen had similar overall response rates (ORRs) and overall survival (OS) to patients receiving 4/2 dosing. However, there was a trend toward inferior time to tumor progression (TTP) with the CDD regimen.
“The median time to progression for the 4/2 schedule was 9.9 months compared with 7.1 months with continuous dosing. Although there wasn’t a statistically significant difference, there was a trend toward superiority with the 4/2 schedule,” said lead study investigator Robert Motzer, MD, who is an attending physician at Memorial Sloan-Kettering Cancer Center, New York, New York. “We felt that this study was important to do because there has been a lot of interest in looking at alternative dosing.”
Motzer, who presented the study findings at the 2011 Genitourinary Cancers Symposium, said these findings are important because they add to the growing body of evidence supporting the approved dosing schedule of sunitinib in advanced RCC. An oral agent, sunitinib is a receptor protein-tyrosine kinase inhibitor that has been shown in a randomized phase 3 trial to provide superior progression-free survival to interferon-alfa (11 vs 5 months) as firstline metastatic RCC therapy. Previous studies have suggested that continuous dosing of sunitinib 37.5 mg has antitumor activity with a manageable safety profile in first- and second-line treatment for metastatic RCC.
Motzer and his colleagues conducted a study comparing the CDD regimen to the 4/2 schedule in 292 patients who had clear cell, locally recurrent, or metastatic disease. Sunitinib was continued until disease progression, unacceptable toxicity, or up to 2 years. The primary end point was TTP, and secondary end points were ORR, OS, and adverse events.
All the patients were randomized (146 patients in each arm) between January 2007 and June 2008. As of October 2010, 289 patients had received sunitinib, and all patients were off therapy. The median age of the patients was 62 years, and 65% were men.
In addition to the increase in TTP, the researchers found that ORR was 32.2% for the 4/2 dosing schedule compared with 28.1% for the CDD regimen. Median OS was 23.1% for the 4/2 dosing group compared with 23.5% for the CDD group.
“We looked at patient-reported outcomes, and we found no difference in quality of life between the 2 dosing schedules, but we found in another analysis of time to progression and time to death that there was a statistically significant improvement with the standard 4/2 schedule compared with continuous dosing,” said Motzer in an interview with The Oncology Pharmacist.
He said the most common drugrelated adverse events were fatigue (62% in both arms), nausea (56% for the 4/2 dosing group vs 49% for the CDD group), and diarrhea (56% for the 4/2 dosing group vs 64% for the CDD group).