The first kinase inhibitor, imatinib mesylate (Gleevec), was approved in 2001 for the treatment of gastrointestinal stromal tumor (GIST).1 Sunitinib maleate (Sutent) is approved for GIST after disease progression or intolerance to imatinib2; and second-generation regorafenib (Stivarga) is approved for locally advanced, unresectable, or metastatic GIST previously treated with imatinib and sunitinib as well as metastatic colorectal cancer.3

Oral agents represent a convenience for patients. Yet, because each agent has a different dosage and recommended route of administration (Table 1), managing treatment can be complex. To be able to counsel patients on what to watch for and when to report signs or symptoms that might require dose interruptions or modifications of imatinib, sunitinib, or regorafenib, a heightened awareness of adverse reactions and warnings and precautions cannot be underestimated.

TABLE 1. Kinase Inhibitors for GIST and Metastatic Colorectal Cancer: Indication, Recommended Dose, and Administration1-3

Continue Reading

(Trade Name)
Indication Recommended Dose Administration
Imatinib mesylate (Gleevec) Kit (CD117) positive unresectable and/or metastatic malignant GIST Adjuvant treatment following resection of Kit (CD117) positive GIST Metastatic and/or unresectable GIST: 400 mg orally, once daily Adjuvant treatment, GIST: 400 mg orally, once daily Mild to moderate hepatic impairment: 400 mg orally, once daily Severe hepatic Take with a meal and a large glass of water Can be dissolved in water or apple juice for patients having difficulty swallowing Daily dosing of 800 mg and above should be accomplished using the 400 mg
Regorafenib (Stivarga) Metastatic CRC previously treated with fluoropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild-type, an anti-EGFR therapy Locally advanced, unresectable, or metastatic GIST previously treated with imatinib mesylate and sunitinib malate 160 mg orally, once daily for the first With a low-fat meal
Sunitinib (Sutent) GIST after disease progression on or intolerance to imatinib mesylate 50 mg orally, once daily, 4 weeks on treatment followed by 2 weeks off Dose interruptions and/or dose adjustments of 12.5 mg recommended based on individual safety and tolerability With or without food
Key: CRC, Colorectal cancer; GIST, Gastrointestinal stromal tumor.

This article summarizes the adverse-effect management information included in the prescribing information for each of the 3 kinase inhibitors. All place women at risk for embryo-fetal toxicity; therefore, women of childbearing potential should use highly effective contraception to avoid becoming pregnant while on these medications and avoid breastfeeding. Both females of childbearing potential and males with female partners of childbearing potential taking regorafenib should continue to use effective contraception for 2 months after the final dose.1-3

For all 3 agents, the most important side effect is the potential to cause serious liver problems that can sometimes lead to death. Patients should inform their oncology nurse if they experience itching2; signs of jaundice, including dark urine1-3; or if they have nausea or vomiting or pain or discomfort in the right upper stomach area.2,3