sunitinib


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SUNItinib

(su-ni-ti-nib) ,

Sutent

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: kinase inhibitors
Pregnancy Category: D

Indications

Gastrointestinal stromal tumor (GIST) that has progressed or intolerance to imatinib.Advanced renal cell carcinoma (RCC).Advanced pancreatic neuroendocrine tumors (pNET).

Action

Inhibits multiple receptor tyrosine kinases, which are enzymes implicated in tumor growth, abnormal vascular growth, and tumor metastases.

Therapeutic effects

Decreased tumor spread.

Pharmacokinetics

Absorption: Well absorbed following oral administration.
Distribution: Unknown.
Protein Binding: Sunitinib—95%; primary active metabolite—90%.
Metabolism and Excretion: Metabolized by the CYP3A4 enzyme system to its primary active metabolite. This metabolite is further metabolized by CYP3A4. Excretion is primarily fecal.
Half-life: Sunitinib—40–60 hr; primary active metabolite—80–110 hr.

Time/action profile (blood levels)

ROUTEONSETPEAKDURATION
POunknown6–12 hr24 hr

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy, lactation;Concurrent use of ketoconazole or St. John's wort.
Use Cautiously in: Hepatic/renal impairment;Concurrent use of bisphosphonates or a history of dental disease (may ↑ risk of jaw osteonecrosis) Obstetric: Childbearing potential; Pediatric: Safety not established.

Adverse Reactions/Side Effects

Central nervous system

  • Reversible Posterior Leukoencephalopathy Syndrome (life-threatening)
  • fatigue (most frequent)
  • dizziness
  • headache

Cardiovascular

  • chf (life-threatening)
  • hypertension (most frequent)
  • peripheral edema
  • QT interval prolongation
  • thromboembolic events

Ear, Eye, Nose, Throat

  • epistaxis (most frequent)

Gastrointestinal

  • hepatotoxicity
  • diarrhea (most frequent)
  • dyspepsia (most frequent)
  • nausea (most frequent)
  • stomatitis (most frequent)
  • vomiting (most frequent)
  • altered taste
  • anorexia
  • cholecystitis
  • constipation
  • esophagitis
  • ↑ lipase/amylase
  • ↑ liver enzymes
  • oral pain

Dermatologic

  • erythema multiforme (life-threatening)
  • alopecia
  • hand-foot syndrome
  • hair color change
  • impaired wound healing
  • rash
  • skin discoloration

Endocrinologic

  • hypothyroidism (most frequent)
  • adrenal insufficiency
  • hyperthyroidism

Fluid and Electrolyte

  • dehydration
  • hypophosphatemia

Hematologic

  • hemorrhage
  • anemia (most frequent)
  • lymphopenia (most frequent)
  • neutropenia (most frequent)
  • thrombocytopenia (most frequent)

Metabolic

  • hyperuricemia (most frequent)

Musculoskeletal

  • arthralgia
  • back pain
  • limb pain
  • myalgia
  • osteonecrosis (primarily of jaw)

Miscellaneous

  • tumor lysis syndrome (life-threatening)
  • fever (most frequent)

Interactions

Drug-Drug interaction

Ketoconazole and other inhibitors of the CYP3A4 enzyme system may ↑ levels and the risk of toxicity; ↓ dose to 37.5 mg daily (for GIST and RCC) or 25 mg daily (for pNET); avoid these strong inhibitors, if possible.Rifampin and other inducers of the CYP3A4 enzyme system may ↓ levels and effectiveness; ↑ dose to 87.5 mg daily (for GIST and RCC) or 62.5 mg daily (for pNET); avoid these strong inducers, if possible.Concurrent use with alendronate, etidronate, ibandronate, pamidronate, risedronate, tiludronate, or zoledronic acid may ↑ risk of jaw osteonecrosis↑ risk of microangiopathic hemolytic anemia when used with bevacizumab (concurrent use not recommended).St. John's wort may ↓ levels and effectiveness; avoid concurrent use.Blood levels and effects are ↑ by grapefruit juice; concurrent use should be avoided.

Route/Dosage

GIST and RCC

Oral (Adults) 50 mg once daily for 4 wk, followed by 2-wk rest; alteration of dose is based on safety/tolerability and is made in 12.5-mg increments/decrements.

pNET

Oral (Adults) 37.5 mg once daily.

Availability

Capsules: 12.5 mg, 25 mg, 37.5 mg, 50 mg

Nursing implications

Nursing assessment

  • Monitor for signs of HF (dyspnea, edema, jugular venous distention) during therapy. Assess left ventricular ejection fraction (LVEF) at baseline and periodically during therapy in patients with cardiac events in the previous 12 mo and a baseline ejection fraction in patients without cardiovascular risk factors. Discontinue sunitinib if signs of HF occur.
  • Monitor for hypertension and treat with standard antihypertensive therapy. If severe hypertension occurs, may discontinue sunitinib until controlled.
  • Monitor ECG and electrolytes periodically during therapy; may cause QT prolongation and torsades de pointes.
  • Lab Test Considerations: Monitor CBC with platelet count and serum chemistries including phosphate at the beginning of each treatment cycle. May cause neutropenia, lymphopenia, anemia, and thrombocytopenia. May cause ↑ creatinine, hypokalemia, hyperuricemia, and ↑ uric acid.
    • Monitor ALT, AST, and bilirubin before starting therapy, during each cycle of treatment, and as clinically indicated. Stop therapy if Grade 3 or 4 drug-related hepatic adverse events occur and discontinue if there is no resolution. Do not restart sunitinib if patients subsequently experience severe changes in liver function tests or have other signs and symptoms of liver failure. May cause ↑ AST, ALT, alkaline phosphatase, total and indirect bilirubin, amylase, and lipase.
    • Monitor thyroid function at baseline and in patients with symptoms of hypothyroidism or hyperthyroidism. May be treated with standard medical practice.

Potential Nursing Diagnoses

Diarrhea (Adverse Reactions)
Nausea (Adverse Reactions)

Implementation

  • Do not confuse sunitinib with sorafenib.
  • Oral: Administer once daily with or without food.

Patient/Family Teaching

  • Instruct patient to take sunitinib as directed. Take missed doses as soon as remembered, but not just before next dose. Take next dose at regular time. Do not take more than 1 dose at a time. Tell your health care professional about the missed dose.
  • Advise patient to avoid grapefruit juice and grapefruit products during therapy.
  • Instruct patient to notify health care professional promptly if signs of liver failure (itching, yellow eyes or skin, dark urine, pain or discomfort in the right upper stomach area) or tumor lysis syndrome (nausea, shortness of breath, irregular heartbeat, clouding of urine, tiredness) occur.
  • Advise patient that GI disorders (diarrhea, nausea, stomatitis, dyspepsia, vomiting) are common and may require antiemetic and antidiarrheal medications.
  • Inform patient that sunitinib may cause discoloration (yellow) of skin and depigmentation of hair or skin.
  • 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.
  • Advise patient to notify health care professional if bleeding or swelling occur.
  • Advise women of childbearing potential to avoid becoming pregnant while receiving sunitinib.

Evaluation/Desired Outcomes

  • Decrease in tumor spread.

sunitinib

a miscellaneous antineoplastic.
indications This drug is used to treat advanced renal carcinoma and GI stromal tumors after disease progression or intolerance to imatinib.
contraindications Pregnancy, lactation, and known hypersensitivity to this drug prohibit its use.
adverse effects Adverse effects of this drug include headache, dizziness, insomnia, fatigue, hypertension, altered taste, constipation, stomatitis, mucositis, skin discoloration, depigmentation of hair or skin, alopecia, pain, arthralgia, myalgia, cough, dyspnea, and electrolyte abnormalities. Life-threatening side effects include central nervous system hemorrhage, seizures, left ventricular dysfunction, hepatotoxicity, vomiting, dyspepsia, pancreatitis, neutropenia, thrombocytopenia, and bleeding. Common side effects include nausea, anorexia, abdominal pain, and rash.
References in periodicals archive ?
Researchers investigating how well the chemotherapy drug sunitinib works against various types of cancer have overestimated the drug's effectiveness by an average of 45 percent, an analysis shows.
diarrhea) especially in initial 3 to 4 months; (2) the Fuhrman nuclear grade 1 RCC could be controlled with the half dose; (3) the patient had a low body weight (50 kg); and (4) we assumed that sunitinib was not suitable for patients scheduled for long-term treatment due to its severe adverse effects, such as hematologic complication compared to sorafenib.
Using reovirus and sunitinib the researchers tested series of human and mouse lung cancer cell lines and concluded that reovirus and sunitinib combination therapy holds promise as a novel treatment strategy for NSCLC.
Makey, Edmund Chinchar, Carissa Howie, and Lucio Miele, all from the University of Mississippi Medical Center, gave obese mice the cancer drug, known as Sunitinib, these mice lost about 70 percent of their fat mass.
But on her return from the Big Apple, she was offered the drug Sunitinib, then a new US brand to the market, which doctors explained would prolong, not save, her life.
She refused to give up hope and took part in a trial of Sunitinib, a drug that starves cancer cells of oxygen.
The first is the use of small-molecule tyrosine kinase inhibitors such as sunitinib or sorafenib to block the intracellular protein kinase activity of the VEGF receptor.
Recently approved drugs for the treatment of kidney cancer include sorafenib (2005), sunitinib (2006), temsirolimus (2007) everolimus (2009), bevacizumab (2009) and pazopanib (2009).
IMPRINT is a global multicenter, randomized, controlled Phase III study in patients with metastatic and/or locally advanced RCC who are candidates for receiving standard first-line therapy with sunitinib (Sutent,Pfizer).
Sunitinib and sorafenib are tyrosine kinase inhibitors (TKIs) targeting growth factor receptors; the most important of these receptors are the vascular endothelial growth factor (VEGF), the platelet derived growth factor (PDGF) and the stem cell factor KIT receptors.
Sorafenib (Nexavar) achieved disease control in 68% of 38 patients who had gastrointestinal stromal tumors (GIST) that was resistant to imatinib and/or sunitinib in a multicenter phase II trial.