瑞格菲尼(Stivarga)

【Function and indications】
Stivarga is a kinase inhibitor indicated for the treatment of patients with metastatic colorectal cancer (CRC) who have previously been treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if KRAS wild-type, an anti-EGFR therapy.

【Model and specifications】
40 mg film-coated tablets.

【Usage and dosage】
(1) Recommended dose: 160 mg orally once daily for the first 21 days of a 28-day course of treatment.

(2) Take Stivarga with food (a low-fat breakfast).

【Clinical studies】

In 2013, the FDA approved a new indication for Stivarga (regorafenib, Tablets) for the treatment of advanced gastrointestinal stromal tumors. Gastrointestinal stromal tumors are a type of tumor that originates from the mesenchymal tissue of the gastrointestinal tract and accounts for the majority of mesenchymal tumors of the digestive tract. Gastrointestinal stromal tumors account for 1-3% of gastrointestinal malignancies, with an estimated annual incidence of approximately 10-20/1 million. They are more common in middle-aged and elderly patients, less common in patients under 40 years old, and there is no significant difference in incidence between men and women.
[Precautions]
(1) Bleeding: Permanently discontinue Stivarga for severe or life-threatening bleeding.
(2) Dermatological toxicity: Interrupt and then reduce or discontinue Stivarga depending on the severity and persistence of dermatological toxicity.
(3) Hypertension: Temporarily or permanently discontinue Stivarga for severe or uncontrolled hypertension.
(4) Cardiac ischemia and infarction: Withhold Stivarga for new or acute cardiac ischemia/infarction and resume only after resolution of the acute ischemic event.
(5) Reversible posterior leukoencephalopathy syndrome (RPLS): Discontinue Stivarga.
(6) Gastrointestinal perforation or fistula: Discontinue Stivarga.
(7) Wound healing complications: Stop Stivarga before surgery. Discontinue in patients with wound dehiscence.
(8) Embryo-fetal toxicity: May cause fetal harm. Advise women of the potential risk to the fetus.

[Adverse Reactions and Contraindications] The most common adverse reactions (≥30%) are fatigue/fatigue, decreased appetite and food intake, hand-foot skin reaction (HFSR) [palmar-plantar erythrodysesthesia (PPE)], diarrhea, oral mucositis, weight loss, infection, hypertension, and dysphonia.

[Contraindications] Nursing mothers: Discontinue the drug or breastfeeding, considering the importance of the drug to the mother.

[Pregnant women use] Nursing mothers: Discontinue the drug or breastfeeding, considering the importance of the drug to the mother.

[Pediatric use] Not recommended.

[Drug interactions] Stivarga is a multikinase inhibitor that blocks multiple enzymes that promote tumor growth. “Stivarga is the third drug approved by the FDA to treat GIST,” said Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. “It provides an important new treatment option for patients with GIST who no longer respond to existing treatments.”
The FDA granted the drug priority review, a program used to review drugs for which no effective alternative treatments exist or that offer a significant improvement over currently available treatments. It was also granted orphan drug designation because it is intended to treat a rare disease.
The safety and efficacy of Stivarga were based on results from a clinical study (Lancet 2013 Jan 26;381(9863):295-302) that evaluated 199 patients with GIST who had progressed after treatment with either Gleevec or sunitinib and had unresectable disease. The patients were randomly assigned to receive Stivarga or placebo. All patients received best supportive care, including treatment for adverse events and cancer-related symptoms.
Patients who received Stivarga or placebo in the study received treatment until their cancer progressed or the adverse reactions were intolerable. The results showed that Stivarga delayed the growth of patients’ tumors (progression-free survival) by an average of 3.9 months longer than those who took placebo (4.8 vs 0.9 months, risk ratio 0.27, P<0.0001). Patients who received placebo had the opportunity to switch to Stivarga treatment after their cancer progressed.
Common adverse reactions in patients treated with Stivarga were weakness and fatigue, hand-foot syndrome, diarrhea, loss of appetite, high blood pressure, mouth ulcers, infections, voice changes, pain, weight loss, stomach pain, rash, fever and nausea. Serious adverse reactions occurred in less than 1% of patients and included liver damage, severe bleeding, blistering and peeling, high blood pressure requiring emergency treatment, heart attack, and intestinal perforation.

[Storage]
Store at room temperature.

[Manufacturer]
Bayer Pharmaceuticals, USA.