Lower doses of regorafenib are being evaluated in 2 clinical trials, 1 in adults 70 years or older with mCRC and 1 in patients 18 years or older with refractory mCRC.3,4

In the first study being conducted in patients 70 years or older, patients are being assigned to receive regorafenib 120 mg daily for 21 days of each 28-day cycle. After the first cycle, patients may be instructed to increase the dose to 160 mg daily for 21 days of the cycle depending on the patient’s health status. The primary outcome is the number of participants who experience grade 3 to 5 toxicity.3


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In the second study (ReDOS), patients are divided into 4 treatment arms, in which patients receive lower-dose or standard-dose regorafenib orally once daily on days 1 to 21 with pre-emptive clobetasol propionate given topically twice daily for 12 weeks or reactive clobetasol propionate for the prevention or treatment of hand–foot skin reactions.4

“The standard arm kept the FDA-approved dose of 160 mg/day and the experimental arm has a starting dose of 80 mg/day with weekly escalations according to tolerability of 40 mg/day until we reach 160 mg/day (goal) or the [maximum tolerated dose],” said Dr. Bekaii-Saab, who is also an investigator on this study.

The primary outcome measure is the proportion of patients in each arm who complete 2 courses of treatment and who plan to begin course 3 if disease progression has not occurred. Secondary outcome measures include progression-free survival, overall survival, and the proportion of patients that experience grade 3 or 4 hand-foot skin reactions or fatigue.4

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“I think these 2 trials are great. They both start at a reduced dose and titrate up as tolerated.  These studies will confirm that the reduced dose has efficacy with less toxicity,” Tara Seery, MD, medical oncologist at UC Irvine Health Chao Family Comprehensive Cancer Center and UC Irvine Health H.H. Chao Comprehensive Digestive Disease Center in Orange, CA, told Cancer Therapy Advisor.

“Stivarga is a good drug but we need to find a dose that limits the side effects. At the 160 mg dose, it is very difficult for patients to remain on therapy,” Dr. Seery concluded.

Reference

  • Stivarga (regorafenib) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc. http://labeling.bayerhealthcare.com/html/products/pi/Stivarga_PI.pdf. 2015. Updated April, 2014. Accessed October 27, 2015.
  • Grothey A, van Cutsem E, Sobrero A, et al. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013;381(9863):303-312.
  • Regorafenib in metastatic colorectal cancer. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT02466009. 2015. Updated June 4, 2015.  Accessed October 27, 2015.
  • Lower or standard dose regorafenib in treating patients with refractory metastatic colorectal cancer. ClinicalTrials.gov website. https://clinicaltrials.gov/ct2/show/NCT02368886. 2015. Updated September 11, 2015.  Accessed October 2, 2015.