Treatment dose optimisation in patients with advanced colorectal cancer treated with regorafenib

This study investigated the effectiveness and safety of increasing doses of regorafenib (Stivarga) doses in patients with advanced colorectal cancer. Researchers suggested that this method with increasing doses should be used to assess the optimal dose for each patient.

Colorectal cancer is the third most common cancer worldwide. A significant number of patients present metastatic (spread to other parts of the body) disease at diagnosis. The standard treatment used to be chemotherapy and radiation therapy. However, in advanced cases, these treatments are only of limited effectiveness.

Regorafenib is a targeted therapy that prevents tumor growth by blocking a specific protein. Prior studies showed that this drug is associated with better outcomes for advanced patients at the expense of a high toxicity. Doctors often change doses to overcome the toxicities without decreasing the anti-tumor effect. However, the effect of lower doses in patients with advanced colorectal cancer is not well known. 

This study included information about 116 patients with metastatic colorectal cancer. Of these 54 patients were assigned to receive increasing doses of regorafenib (group 1) and 62 the standard dosage (group 2). Patients in group 1 received increased doses of regorafenib until unacceptable side effects. The average follow-up time was 1.18 years.

23 of 54 patients (43%) in group 1 received the third cycle of treatment. This was compared to 16 of 62 (26%) patients in group 2 who initiated the third cycle of treatment. More patients in group 1 initiated the third cycle of therapy due to a lower toxicity (and the same anti-tumor effect).

The most common side effects were fatigue (tiredness; 13% in group 1 and 18% in group 2) and hand-foot skin reaction (15% in group 1 and 16% in group 2). Abdominal pain and hypertension (increased blood pressure) were also common effects. 14 patients had at least one severe effect (6 in group 1 and 8 in group 2). There was one death by heart attack in group 2 probable related to treatment. 

This study concluded that dose increasing tests should be used to decide the best treatment dose of regorafenib for patients with advanced colorectal cancer.

This study was funded by Bayer Healthcare Pharmaceuticals, the manufacturer of regorafenib.