Regorafenib

Other name

-

International/Other brands

Stivarga

Groups

Approved

Structure

Prescription products

Target

EGFR

Description

Regorafenib is an orally-administered inhibitor of multiple kinases. It is used for the treatment of metastatic colorectal cancer and advanced gastrointestinal stromal tumours. FDA approved on September 27, 2012. Approved use of Regorafenib was expanded to treat Hepatocellular Carcinoma in April, 2017.

Indications

Metastatic Gastrointestinal Stromal Tumor; Locally advanced Gastrointestinal stromal tumor; Refractory, metastatic Colorectal cancer; Unresectable Gastrointestinal stromal tumor

Other indications

-

Mechaism of action

-

Absorption

Cmax = 2.5 μg/mL; Tmax = 4 hours; AUC = 70.4 μgh/mL; Cmax, steady-state = 3.9 μg/mL; AUC, steady-state = 58.3 μgh/mL; The mean relative bioavailability of tablets compared to an oral solution is 69% to 83%.

Metabolism

Regorafenib is metabolized by CYP3A4 and UGT1A9. The main circulating metabolites of regorafenib measured at steady-state in human plasma are M-2 (N-oxide) and M-5 (N-oxide and N-desmethyl), both of them having similar in vitro pharmacological activity and steady-state concentrations as regorafenib. M-2 and M-5 are highly protein bound (99.8% and 99.95%, respectively).

Toxicity

The most common adverse reactions (≥20%) are asthenia/fatigue, HFSR, diarrhea, decreased appetite/food intake, hypertension, mucositis, dysphonia, and infection, pain (not otherwise specified), decreased weight, gastrointestinal and abdominal pain, rash, fever, and nausea