Nibinase

GI stromal tumor (GIST) after failure of imatinib mesylate treatment due to resistance or intolerance. Advanced &/or metastatic renal cell carcinoma (MRCC). Unresectable or metastatic well-differentiated pancreatic neuroendocrine tumors (pNET) w/ disease progression. Adjuvant treatment of adults at high risk of recurrent renal cell carcinoma (RCC) following nephrectomy.

GIST & MRCC 50 mg once daily for 4 consecutive wk followed by 2-wk off period (schedule 4/2) to complete a 6-wk cycle. Dose modification: 12.5 mg increments or decrements may be applied based on individual safety & tolerability up to 75 mg or down to 25 mg. pNET 37.5 mg once daily w/o scheduled rest period. Dose modification: 12.5 mg increments or decrements may be applied based on individual safety & tolerability. Max dose in Phase 3: 50 mg daily. Adjuvant treatment of RCC 50 mg once daily on schedule 4/2 for nine 6-wk cycles (approx 1 yr). Dose modification: 12.5 mg decrements may be applied based on individual safety & tolerability down to 37.5 mg. Max dose in Phase 3: 50 mg daily. Co-administration w/ strong CYP3A4 inducers (eg, rifampicin) May be increased in 12.5 mg increments to a max of 87.5 mg (GIST & RCC) or 62.5 mg (pNET) daily. Co-administration w/ strong CYP3A4 inhibitors (eg, ketoconazole) May be reduced to 12.5 mg decrements to a min of 37.5 mg (GIST & RCC) or 25 mg (pNET) daily.

May be taken with or without food.

Hypersensitivity.

Depigmentation of hair or skin may occur during treatment. Discontinue if SJS or erythema multiforme (eg, progressive skin rash often w/ blisters or mucosal lesions); pancreatitis; necrotizing fasciitis, thrombotic microangiopathy, nephrotic syndrome; clinical manifestations of CHF occur. Not for patients w/ NSCLC. Routine assessment for treatment-emergent bleeding events should include CBC & physical exam. Patients w/ intra-abdominal malignancies. Supportive care for GI adverse events requiring treatment may include anti-emetic or anti-diarrheal medication. Monitor LFTs (ALT, AST, bilirubin levels) before initiation of treatment, during each cycle of treatment, & as clinically indicated; patients at risk of tumor lysis syndrome w/ high tumor burden. Regularly check blood glucose levels in diabetics. Interrupt treatment for Grade 3 or 4 hepatic-related adverse events & discontinue if there is no resolution. Temporary suspension in patients w/ severe HTN that is not controlled w/ medical management; seizures; undergoing major surgical procedures. Perform CBC at the start of each treatment cycle. Patients who are at risk for or who have history of CV events eg, heart failure, cardiomyopathy, myocardial ischemia & MI. Carefully monitor for clinical signs & symptoms of CHF; development or worsening of proteinuria. Consider baseline & periodic LVEF evaluations; baseline evaluation of ejection fraction in patients w/o cardiac risk factors. Patients w/ known history of QT interval prolongation, taking antiarrhythmics, or w/ relevant preexisting cardiac disease, bradycardia or electrolyte disturbances. Concomitant treatment w/ strong CYP3A4 inhibitors; IV bisphosphonates. Screen patients for HTN & control as appropriate. Baseline lab measurement of thyroid function, & baseline urinalysis are recommended. Treat hypo- or hyperthyroidism, & signs & symptoms suggestive of thyroid dysfunction prior to start of therapy. Patients w/ seizures & signs/symptoms consistent w/ reversible posterior leukoencephalopathy syndrome (RPLS) eg, HTN, headache, decreased alertness, altered mental functioning & visual loss including cortical blindness. Consider dental exam & appropriate preventive dentistry prior to treatment. Avoid invasive dental procedures. May affect ability to drive & use machines. May compromise male & female fertility. Women of childbearing potential should avoid becoming pregnant. Not to be used during pregnancy or in any woman not using adequate contraception. Not to breast-feed while on treatment. Paed.

Neutropenia, thrombocytopenia, anaemia, leukopenia, lymphopenia; hypothyroidism; decreased appetite, dehydration; insomnia, depression; headache, dizziness, taste disturbance (including dysgeusia, ageusia), paraesthesia; HTN; dyspnoea, epistaxis, dyspnoea, pharyngolaryngeal pain; abdominal pain, diarrhoea, nausea, vomiting, constipation, stomatitis (including aphthous stomatitis), dyspepsia, flatulence, GERD, glossodynia, oral pain; skin discolouration (including yellow skin), palmar-plantar erythrodysaesthesia syndrome, rash, dry skin, hair colour changes, erythema, alopecia, pruritus; pain in extremity, myalgia, arthralgia; fatigue, oedema, mucosal inflammation, asthenia, pyrexia, chills. Abdominal distention, dry mouth, gingival bleeding, oesophagitis, gingival bleeding; blister, exfoliative dermatitis, nail disorder, skin exfoliation, lesion & reaction; periorbital & eyelid oedema, increased lacrimation; pleural effusion; DVT; flu-like illness; oropharyngeal pain; proteinuria, chromaturia. Pancreatitis, GI perforation; hypersensitivity reactions (including angioedema), eczema, pyoderma gangrenosum, erythema multiforme; resp (including pneumonia, bronchitis), skin, bacterial & fungal infections, UTI, sepsis/septic shock, oral/genital/anorectal/skin/limb/visceral abscess; cardiac disorders eg, cardiac failure, CHF, prolonged QT interval, Torsade de pointes, cardiomyopathy, myocardial ischemia, left ventricular infarction, MI, decreased/abnormal ejection fraction; vascular disorders (including arterial thromboembolic events & VTE); hemorrhagic events; pulmonary embolism; renal impairment &/or failure; hepatic failure & cholecystitis (particularly acalculous cholecystitis); decreased wt, WBC, & platelet count, Hb, increased lipase, amylase, AST, ALT, blood creatinine phosphokinase, TSH, uric acid & glucose. SJS.

Increased (sunitinib + primary active metabolite) C_max & AUC_0-∞ w/ strong CYP3A4 inhibitor eg, ketoconazole. Increased conc w/ strong CYP3A4 inhibitors (eg, ritonavir, itraconazole, erythromycin, clarithromycin, grapefruit juice). Reduced (sunitinib + primary active metabolite) C_max & AUC_0-∞ w/ CYP3A4 inducer eg, rifampicin. Decreased conc w/ strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, phenobarb or St. John's wort (Hypericum perforatum).

Targeted Cancer Therapy

L01EX01 - sunitinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

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