Bdfoie 4/Bdfoie 10

Monotherapy for the treatment of progressive, locally advanced or metastatic, differentiated (papillary/follicular/Hürthle cell) thyroid carcinoma (DTC), refractory to radioactive iodine (RAI) in adults. Monotherapy for the treatment of advanced or unresectable hepatocellular carcinoma (HCC) in adults who have received no prior systemic therapy. In combination w/ pembrolizumab for the treatment of advanced or recurrent endometrial carcinoma (EC) in adults who have disease progression on or following prior treatment w/ platinum-containing therapy in any setting & are not candidates for curative surgery or radiation.

DTC 24 mg once daily. Dose modification: 1st dose reduction: 20 mg once daily; 2nd dose reduction: 14 mg once daily; 3rd dose reduction: 10 mg once daily. HCC Patient weighing ≥60 kg 12 mg once daily. Dose modification: 1st occurrence: 8 mg once daily; 2nd occurrence: 4 mg once daily; 3rd occurrence: 4 mg every other day, <60 kg 8 mg once daily. Dose modification: 1st occurrence: 4 mg once daily; 2nd occurrence: 4 mg every other day; 3rd occurrence: Discontinue use. EC Initially 20 mg once daily, in combination w/ pembrolizumab either 200 mg every 3 wk or 400 mg every 6 wk, administered as IV infusion over 30 min, until unacceptable toxicity or disease progression. Dose modification: 1st occurrence: 14 mg once daily; 2nd occurrence: 10 mg once daily; 3rd occurrence: 8 mg once daily. DTC patient ≥75 yr, Asian, w/ comorbidities (eg, HTN, & hepatic or renal impairment), weighing <60 kg 24 mg. HCC patient other than w/ moderate & severe hepatic impairment or severe renal impairment Initiate treatment at 12 mg for patient weighing ≥60 kg & 8 mg for patient weighing <60 kg. DTC in patients w/ severe (Child-Pugh C) hepatic impairment Initially 14 mg once daily. EC in patients w/ severe (Child-Pugh C) hepatic impairment Initially 10 mg once daily. DTC in patient w/ severe renal impairment Initially 14 mg once daily. EC in patient w/ severe renal impairment Initially 10 mg once daily.

May be taken with or without food: Take at the same time each day. Swallow whole w/ water. Alternatively, add cap (w/o breaking or crushing the cap) to 1 tbsp of water/apple juice in a small glass & leave for at least 10 min. Stir susp for at least 3 min & drink immediately. Rinse glass w/ another 1 tbsp of water/apple juice & drink.

Hypersensitivity.

HTN; proteinuria, cases of nephrotic syndrome. BP should be well-controlled prior to treatment & if patients are known to be hypertensive, stable dose of antihypertensive therapy for at least 1 wk prior to treatment. May promote formation of aneurysms &/or artery dissections. Monitor urine protein regularly. Discontinue in the event of nephrotic syndrome; persistence of grade 4 diarrhea despite medical management. Increased in ALT, AST & blood bilirubin; hepatic failure & acute hepatitis; hepatic encephalopathy in HCC patients. Monitor overall safety in patients w/ mild or moderate hepatic impairment & LFTs prior to initiation of treatment, then every 2 wk for the 1st 2 mth & mthly thereafter during treatment. Monitor for worsening liver function including hepatic encephalopathy in patients w/ HCC. Adjust initial dose if patients have severe renal impairment. Institute prompt medical management of diarrhea to prevent dehydration. Monitor patients for clinical symptoms or signs of cardiac decompensation. Posterior reversible encephalopathy syndrome/reversible posterior leucoencephalopathy syndrome. Patients who have had arterial thromboembolism w/in the previous 6 mth. Discontinue following arterial thrombotic event. May increase risk of thromboembolic events when combined w/ OCs. Serious tumour related bleeds including fatal hemorrhagic events. Reported GI perforation or fistula. Increased risk for the development of fistula. Monitor ECG at baseline & periodically during treatment. Monitor & correct electrolyte abnormalities prior to treatment. Monitor thyroid function before initiation of, & periodically throughout treatment. Impairs exogenous thyroid suppression. Temporary interruption of treatment should be considered in patients undergoing major surgical procedures. Osteonecrosis of the jaw in patients who had received prior or concomitant treatment w/ antiresorptive bone therapy, &/or other angiogenesis inhibitors eg, bevacizumab, TKI, mTOR inhibitors. Avoid invasive dental procedures if possible in patients who have previously received or are receiving IV bisphosphonates. Potential risk for additive toxicities following sorafenib or other anticancer treatments. Minor influence on the ability to drive & use machines. Avoid becoming pregnant & use highly effective contraception while on treatment & for at least 1 mth after finishing treatment in women of childbearing potential. Not to be used during pregnancy unless clearly necessary. Contraindicated during lactation. Limited data for patients of ethnic origin other than Caucasian or Asian. Safety & efficacy have not yet been established in childn 2-<18 yr. Not to be used in childn <2 yr. Limited data in elderly ≥75 yr.

UTI; thrombocytopenia, leukopenia, neutropenia; hypothyroidism; hypocalcemia, hypokalemia, decreased wt & appetite; insomnia; dizziness, headache, dysgeusia; hemorrhage, HTN, hypotension; dysphonia; diarrhea, GI & abdominal pains, vomiting, nausea, oral inflammation & pain, constipation, dyspepsia, dry mouth; increased blood bilirubin, hypoalbuminemia, increased ALT & AST; palmar-plantar erythrodysesthesia syndrome, rash, alopecia; back pain, arthralgia, myalgia, pain in extremity, musculoskeletal pain; proteinuria; fatigue, asthenia, peripheral edema. Lymphopenia; increased blood TSH; dehydration, hypomagnesemia, hypercholesterolemia; CVA; MI, cardiac failure, prolonged ECG QT, decreased ejection fraction; pulmonary embolism; anal fistula, flatulence, increased lipase & amylase; hepatic failure, hepatic encephalopathy, increased blood alkaline phosphatase, abnormal hepatic function, increased γ-glutamyltransferase, cholecystitis; hyperkeratosis; renal failure, renal impairment, increased blood creatinine & blood urea; malaise.

May reduce effectiveness of hormonal contraceptives/OCs.

Targeted Cancer Therapy

L01EX08 - lenvatinib ; Belongs to the class of other protein kinase inhibitors. Used in the treatment of cancer.

Rx