(re-goe-raf-e-nib) ,


(trade name)


Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D


Metastatic colorectal cancer (CRC) that has failed previous treatment that included a fluoropyrimidine, oxiplatin, irinotecan, an anti-VEGF therapy, and additional anti-EGFR therapy if tumor is of the KRAS wild type.


Inhibits kinases, which are responsible for many phases of cell function and proliferation.

Therapeutic effects

Decreased progression of metastatic CRC with improved survival.


Absorption: Well absorbed following oral administration (69–83%).
Distribution: Unknown.
Protein Binding: Regorafenib—>99.5%, M-2 metabolite—99.8%, M-5 metabolite—99.95%.
Metabolism and Excretion: Highly metabolized (by CYP3A4 and UGT1A9), 2 metabolites (M-2 and M-5) have antineoplastic activity. Undergoes enterohepatic circulation.
Half-life: Regorafenib—28 hr (range 14–58 hr), M-2 metabolite—25 hr (range 14–32 hr), M-5 metabolite—51 hr (range 32–70 hr). 47% excreted in feces as parent compound, 24% as metabolites; 19% excreted in urine (mostly as inactive metabolites).

Time/action profile (improved survival)

PO3 mo3 moup to 10 mo


Contraindicated in: Avoid strong inducers/inhibitors of CYP3A4; Lactation: Breast feeding should be avoided; Obstetric: May cause fetal harm, pregnancy should be avoided;Severe hepatic impairment (Child-Pugh Class C).
Use Cautiously in: History of hypertension/cardiovascular disease (BP should be controlled prior to treatment);Elective surgical procedures (discontinue 2 wk prior to surgery);Patients with reproductive potential (effective contraception should be practiced during and for 2 mo following treatment); Pediatric: Safe and effective use in children <18 yr has not been established.

Adverse Reactions/Side Effects

Central nervous system

  • reversible posterior leukoencephalopathy (life-threatening)
  • fatigue (most frequent)
  • headache

Ear, Eye, Nose, Throat

  • dysphonia (most frequent)


  • cardiac ischemia/infarction (life-threatening)
  • hypertension


  • gastrointestinal fistula/perforation (life-threatening)
  • hepatotoxicity (life-threatening)
  • ↓ appetite (most frequent)
  • diarrhea (most frequent)
  • mucositis (most frequent)
  • altered taste
  • dry mouth
  • gastrointestinal reflux
  • ↑ transaminases


  • plantar erythrodysthesia (life-threatening)
  • alopecia
  • impaired wound healing
  • rash


  • hypothyroidism

Fluid and Electrolyte

  • hypocalcemia (most frequent)
  • hypokalemia (most frequent)
  • hypophosphatemia (most frequent)
  • hyponatremia


  • proteinuria (most frequent)


  • bleeding
  • thrombocytopenia
  • anemia (most frequent)
  • lymphopenia (most frequent)


  • weight loss (most frequent)
  • ↑ lipase (most frequent)
  • ↑ amylase


  • pain (most frequent)
  • musculoskeletal stiffness


  • tremor


  • infection
  • fever (most frequent)


Drug-Drug interaction

Strong inhibitors of CYP3A4 including clarithromycin, itraconazole, ketoconazole, posaconazole, telithromycin, and voriconazole ↑blood levels and the risk of toxicity, avoid concurrent use.Strong inducers of CYP3A4 including carbamazepine, phenobarbital, phenytoin, and rifampin ↓ blood levels and effectiveness, avoid concurrent use.May ↑ risk of bleeding with warfarin.St. John's wort ↓ blood levels and effectiveness, avoid concurrent use.Grapefruit juice ↑ blood levels and the risk of toxicity, avoid concurrent use.


Oral (Adults) 160 mg daily on days 1–21 of a 28-day cycle (with low-fat meal containing <30% fat). Dose modifications required for hematologic toxicity, dermatologic toxicity, or hypertension. Discontinuation may be necessary for life-threatening toxicities.


Tablets: 40 mg

Nursing implications

Nursing assessment

  • Monitor BP prior to and weekly during the first 6 wk, then every cycle of therapy. Do not initiate regorafenib until BP is well controlled.
  • Assess for cardiac ischemia or infarction during therapy.
  • Assess for bleeding during therapy. Interrupt therapy if severe hemorrhage occurs.
  • Lab Test Considerations: Obtain liver function test (ALT, AST, bilirubin) before starting, at least every 2 wk during first 2 mo of therapy, and monthly thereafter. Monitor liver function tests weekly in patients with ↑ liver function tests until improvement to <3 × the upper limit of normal or baseline.
    • May cause anemia, thrombocytopenia, neutropenia, and lymphopenia.
    • May cause hypocalcemia, hypokalemia, hyponatremia, and hypophosphatemia.
    • May cause proteinuria, ↑ serum lipase, and ↑ serum amylase.
    • May cause ↑ INR. Monitor INR levels more frequently in patients receiving warfarin.

Potential Nursing Diagnoses

Risk for impaired skin integrity
Deficient knowledge, related to medication regimen (Patient/Family Teaching)


  • high alert: Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order and dose calculations. Therapy should be initiated by physician experienced in the treatment of patients with colorectal cancer.
  • Oral: Administer four 40 mg tablets once daily for the first 21 days of the of each 28-day cycle. Swallow tablets whole with a low-fat breakfast that contains <30% fat such as 2 slices of white toast with 1 tbsp of low-fat margarine and 1 tbsp of jelly, and 8 oz of skim milk; or 1 cup of cereal, 8 oz skim milk, 1 slice toast with jam, apple juice, and 1 cup coffee or tea.
  • Dose modifications:: Interrupt therapy for Grade 2 hand-foot skin reaction (HFSR) that is recurrent or does not improve in 7 days despite dose reduction; interrupt therapy for a minimum of 7 days for Grade 3 (HFSR), symptomatic Grade 2 hypertension, any Grade 3 or 4 adverse reactions.
    • Reduce dose to 120 mg daily for first occurrence of Grade 2 HFSR of any duration, after first recovery of any Grade 3 or 4 adverse reaction, for Grade 3 ↑ AST or ALT; only resume if potential benefit outweighs risk of hepatotoxicity.
    • Reduce dose to 80 mg daily for re-occuuence of Grade 2 HFSR at 120 mg dose, after recovery of any Grade 3 or 4 adverse reaction at 120 mg dose (except hepatotoxicity).
    • Discontinue regorafenib permanently for failure to tolerate 80 mg dose, any occurrence of ↑ AST or ALT >20 × upper limit of normal, any occurrence of ↑ AST or ALT >3 × upper limit of normal with concurrent bilirubin >2 × upper limit of normal, re-occurrence of ↑ AST or ALT >5 × upper limit of normal despite reduction to 120 mg dose, any Grade 4 adverse reaction; only resume if the potential benefits outweigh the risks.

Patient/Family Teaching

  • Instruct patient to take tablets at the same time each day with a low-fat meal. Take missed doses on the same day as soon as remembered; do not take 2 doses on the same day to make up for a missed dose. Store medicine in original container; do not place in daily or weekly pill boxes. Discard remaining tablets 28 days after opening bottle. Tightly close bottle after each opening and keep desiccant in bottle.
  • Advise patient to avoid drinking grapefruit juice or eating grapefruit during regorafenib therapy.
  • Advise patient to notify health care professional immediately if signs and symptoms of liver problems (yellowing of skin or white part of eyes, nausea, vomiting, dark tea-colored urine, change in sleep pattern), bleeding, skin changes (redness, pain, blisters, bleeding, swelling), hypertension (severe headache, lightheadedness, neurologic symptoms), myocardial ischemia or infarction (chest pain, shortness of breath, dizziness, fainting), or GI perforation or fistula (severe abdominal pain, persistent swelling of abdomen, high fever, chills, nausea, vomiting, severe diarrhea, dehydration) occur.
  • Advise patient to notify health care provider of therapy prior to surgery or if had recent surgery.
  • Advise patient to maintain adequate hydration to minimize risk and to notify health care professional promptly if signs and symptoms of reversible posterior leukoencephalopathy syndrome (RPLS) (headache, seizures, weakness, confusion, high BP, blindness or change in vision, problems thinking) occur.
  • Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications, especially St. John's Wort.
  • Inform female patient that regorafenib can cause fetal harm. Advise women with reproductive potential and men of the need for effective contraception during and for at least 2 mo after completion of therapy. Notify health care provider immediately if pregnancy is planned or suspected or if breast feeding.
  • Emphasize importance of monitoring lab values to monitor for adverse reactions.

Evaluation/Desired Outcomes

  • Decreased progression of metastatic CRC.
Drug Guide, © 2015 Farlex and Partners
References in periodicals archive ?
Food and Drug Administration (FDA) for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib. In addition to the INVICTUS data, Deciphera will also be submitting in its NDA supportive data from the ongoing Phase 1 clinical study, which will include the updated data from GIST patients at doses of >100mg of ripretinib.
Deciphera also announced positive top-line results from its INVICTUS pivotal Phase 3 clinical study supporting a potential new drug application submission to the US Food and Drug Administration for ripretinib for the treatment of patients with advanced GIST who have received prior treatment with imatinib, sunitinib and regorafenib.
Deciphera expects to submit an NDA to the FDA in the first quarter of 2020 for the treatment of patients with advanced gastrointestinal stromal tumors who have receive prior treatment with Imatinib, Sunitinib and Regorafenib.
The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter study to evaluate the safety, tolerability and efficacy of ripretinib compared to placebo in 129 patients with advanced GIST whose previous therapies have included at least imatinib, sunitinib, and regorafenib. The INVICTUS study achieved its primary endpoint of improved PFS as determined by blinded independent central radiologic review using modified Response Evaluation Criteria in Solid Tumors, or RECIST, version 1.1.
("Ono") announced today the three companies have entered into a clinical collaboration agreement to evaluate the combination of Bayer's kinase inhibitor Stivarga[R] (regorafenib) and Bristol-Myers Squibb's / Ono's anti-PD-1 immune checkpoint inhibitor, Opdivo[R] (nivolumab) in patients with micro-satellite stable metastatic colorectal cancer (MSS mCRC), the most common form of mCRC.
The company added that the study is designed to evaluate the safety and efficacy of avapritinib as a third-line or fourth-line treatment for patients with gastrointestinal stromal tumours (GIST) when compared with regorafenib, the current standard of care treatment for GIST.
Four Iranian-produced drugs for cancer and diabetes treatment, including Regorafenib and Sorafenib, were unveiled during a ceremony this morning at Eshtehard Industrial Town in Alborz Province.
In cases of imatinib resistance, second-line treatment with sunitinib and regorafenib has been approved.
Analysis of circulating DNA and protein biomarkers to predict the clinical activity of regorafenib and assess prognosis in patients with metastatic colorectal cancer: a retrospective, exploratory analysis of the CORRECT trial.
The recent advances in the development of targeted anticancer therapies, including sorafenib, regorafenib, lenvatinib and the immune checkpoint inhibitor nivolumab can only be deployed to reduce the burden of morbidity and mortality from HCC in sub Saharan Africa if there are ardent efforts to ensure their availability at prices that are within the reach of patients in this region.
Regorafenib impairs mitochondrial functions, activates AMP-activated protein kinase, induces autophagy, and causes rat hepatocyte necrosis.