BC Cancer Protocol Summary for Therapy for Locally Recurrent or Metastatic, RAI-refractory Differentiated Thyroid Cancer Using Lenvatinib

Transcription

1 BC Cancer Protocol Summary f Therapy f Locally Recurrent Metastatic, RAI-refracty Differentiated Thyroid Cancer Using Lenvatinib Protocol Code Tumour Group Contact Physician UHNOTLEN Head and Neck Dr. Cheryl Ho ELIGIBILITY: Locally recurrent metastatic differentiated thyroid cancer refracty to radioiodine Treatment naïve one pri TKI therapy (SORAfenib, SUNItinib, PAZOpanib) ECOG 0 to 2 Adequately controlled: blood pressure, renal and liver function TSH less than equal to 0.5 miu/l A BC Cancer Compassionate Access Program fm with appropriate clinical infmation f each patient must be submitted and approved pri to treatment. EXCLUSIONS: Anaplastic medullary thyroid cancer Significant cardiovascular gastrointestinal dysfunction Proteinuria than equal to 1 g/24h Histy of significant thrombosis Pre-existing significant QTc prolongation TESTS: Baseline: CBC/differential, serum creatinine, liver enzymes (Alkaline phosphatase, AST, ALT, total bilirubin, albumin), electrolytes (potassium, magnesium, calcium), urine protein, TSH, blood pressure, echocardiogram (ECG) Every two weeks f first 2 months: blood pressure, liver enzymes Monthly during treatment: liver enzymes, TSH, blood pressure, urine protein Befe each Doct s appointment: CBC/differential, serum creatinine, liver enzymes, potassium, calcium, magnesium, blood pressure, urine protein, TSH If clinically indicated: ECG PREMEDICATIONS: Antiemetic protocol f low-moderate emetogenic chemotherapy protocols (see SCNAUSEA) BC Cancer Protocol Summary UHNOTLEN Page 1 of 6 Warning: The infmation contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care treatment. Use of these documents is at

2 TREATMENT: Drug Dose BC Cancer Administration Guideline lenvatinib 24 mg PO once daily Repeat every 30 days (one cycle). Continue until toxicity disease progression. Consider starting at 14 mg/day and escalate de-escalate as tolerated. DOSE MODIFICATIONS Table 1 Persistent intolerable Grade 2 3 adverse reactions Grade 4 lab abnmalities Adverse Reaction Modification Adjusted Dose* First occurrence Second occurrence** Third occurrence** Hold dose until resolved to Grade 0 to 1 baseline 20 mg one daily 14 mg once daily 10 mg once daily * Reduce dose in succession based on pri dose level (24 mg, 20 mg, 14 mg daily); do not increase dose after dose reductions have been made. ** refers to the same a different adverse reaction that requires dose modification Table 2 Hematology ANC (x10 9 /L) Platelets (x10 9 /L) Dose Greater than equal to 1 and Greater than equal to % Less than 1 Less than 75 Delay BC Cancer Protocol Summary UHNOTLEN Page 2 of 6 Warning: The infmation contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care treatment. Use of these documents is at

3 Table 3 Hepatotoxicity: No dose modifications with mild moderate hepatic impairment (Child-Pugh A B). With severe impairment (Child-Pugh C), use 14 mg once daily. Adverse event Grade 1 Alkaline Phosphatase than to 2.5 X AST ALT Total bilirubin than to 3 X than to 3 X than to 1.5 X Dose No adjustment Grade 2 Grade 3 than 2.5 to 5 X than 5 to 20 X than 3 to 5 X than 5 to 20 X than 3 to 5 X than 5 to 20 X than 1.5 to 3 X than 3 to 10 X No adjustment reduce to 14 mg (max.) daily lower Grade 4 than 20 X than 20 X than 20 X than 10 X discontinue Table 4 Renal impairment: Adverse event Grades 1 and 2 egfr CrCl than equal to 30 ml/min Dose Maintain dose physician s discretion Grade 3 29 to 15 ml/min 14 mg once daily physician s discretion Grade 4 less than 15 ml/min; dialysis indicated discontinue BC Cancer Protocol Summary UHNOTLEN Page 3 of 6 Warning: The infmation contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care treatment. Use of these documents is at

4 Table 5 - Diarrhea: See Table 1 f dose modifications Adverse event Grade 1 Grade 2 Grade 3 Grade 4 Diarrhea Increase of <4 stools per day over baseline; mild increase in ostomy output compared to baseline Increase of 4 to 6 stools per day over baseline; moderate increase in output compared to baseline Increase of than equal to 7 stools per day over baseline; incontinence; hospitalization indicated Life-threatening Table 6 - Proteinuria: hold treatment f than 1 g/24 h Adverse event Proteinuria Dose Grade 1 Grade 2 Grade 3 * see Table 1 1+ <1 g/24h 2+ 1 to 3.4 g/24h than equal to 3.5 g/24h Maintain dose Hold until proteinuria less than 1 g/24h; monit every 2 weeks; resume at reduced dose* discontinue Table 7 QT Prolongation: Adverse event QT Prolongation Dose Grade 1 QTc 450 to 480 ms Maintain dose Grade 2 QTc 481 to 500 ms Assess risk f developing TdP; maintain dose reduce dose* BC Cancer Protocol Summary UHNOTLEN Page 4 of 6 Warning: The infmation contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care treatment. Use of these documents is at

5 Grade 3 Grade 4 QTc than equal to 501 ms on 2 separate ECGs QTc than equal to 501 ms than 60 ms from baseline signs and symptoms of serious arrhythmia Hold until Grade 1 baseline; resume at reduced dose* discontinue * see Table 1 PRECAUTIONS: 1. Neutropenia: Fever other evidence of infection must be assessed promptly and treated aggressively. Refer to BC Cancer Febrile Neutropenia Guidelines. There are no dose modifications f lenvatinib. 2. Hypertension: Patients with hypertension should exercise caution while on Lenvatinib. Rigous treatment of blood pressure is necessary, since Lenvatinib can cause a rapid onset of high blood pressure. Tempary suspension of Lenvatinib is recommended f patients with severe hypertension ( than 160 mmhg systolic than 100 mmhg diastolic). Treatment with Lenvatinib may be resumed once hypertension is controlled (see also It is recommended that f at least the first 2 cycles of treatment patients monit their blood pressure daily (home measurements, GP s office, etc. and keep a journal of their blood pressure measurements that can be submitted to the physician at the next appointment. 3. Renal toxicity: Primary risk fact was dehydration/hypovolemia secondary to diarrhea and vomiting; encourage al hydration. 4. Hepatotoxicity: Liver enzymes should be monited befe treatment, every two weeks f the first two months, then monthly thereafter during treatment. Lenvatinib is neither a strong inducer n inhibit of cytochrome P450 3A in the liver. It may be co-administered without dose adjustment with CYP3A inhibits and inducers, P- glycoprotein inhibits and inducers, BCRP inhibits. 5. Posteri Reversible Encephalopathy Syndrome (PRES): MRI to confirm diagnosis. If patients present with headache, seizure, lethargy, confusion, altered mental function, blindness, other visual neurological disturbances, consider dose interruptions, adjustments, discontinuation. 6. Risk of nosebleeds would require dose interruptions, adjustments discontinuation. 7. Gastrointestinal perfation and fistula fmation: Upon development, discontinue. 8. Arterial venous thromboembolic event: Assess a patient s risk f myocardial infarction hemrhagic stroke pri to initiation of treatment. Discontinue lenvatinib following an arterial thrombotic event. 9. Weight loss secondary to decreased appetite, diarrhea 10. Risk of prolonged QT interval; monit ECG, and electrolytes regularly. Hold lenvatinib f QTc than equal to 500 ms. BC Cancer Protocol Summary UHNOTLEN Page 5 of 6 Warning: The infmation contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care treatment. Use of these documents is at

6 Call Dr. Cheryl Ho tumour group delegate at (604) with any problems questions regarding this treatment program. References: 1. Schlumberger M, Tahara M, Wirth LJ, et.al. Lenvatinib versus placebo in radioiodine-refracty thyroid cancer. N Engl J Med 2015;372: Schlumberger M, Tahara M, Wirth LJ, et.al. Supplementary Appendix to Lenvatinib versus placebo in radioiodine-refracty thyroid cancer. N Engl J Med 2015;372: Pan-Canadian Oncology Drug Review. Lenvatinib.Final Recommendation_September Shumaker RC, Zhou M, Ren M, et.al. Effect of lenvatinib (E7080) on QTc interval: results from a though QT study in healthy volunteers. Cancer Chemother Pharmacol 2014;73: BC Cancer Protocol Summary UHNOTLEN Page 6 of 6 Warning: The infmation contained in these documents are a statement of consensus of BC Cancer professionals regarding their views of currently accepted approaches to treatment. Any clinician seeking to apply consult these documents is expected to use independent medical judgement in the context of individual clinical circumstances to determine any patient's care treatment. Use of these documents is at