Regimen : Pazopanib for advanced Renal Cell Carcinoma (RCC)

Transcription

1 Regimen : Pazopanib for advanced Renal Cell Carcinoma (RCC) Indication First line treatment of patients with advanced RCC who: have not received prior cytokine therapy AND Regimen detail Administration have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (NICE TA215) Drug Dose Route Pazopanib 800mg once daily* Oral * if it is necessary to reduce the dose, dose s should be made in steps of 200mg. Pazopanib (Votrient ) is available as 200mg and 400mg tablets. Pazopanib should be taken on an empty stomach, at least one hour before or two hours after a meal. Tablets should be taken whole with water and not broken or crushed. If a dose is missed or the patient vomits after taking their dose, the patient should not be given an additional dose. The patient should take the usual prescribed dose on the following day. Frequency Emetogenicity Additional recommended supportive medication Pre-treatment evaluation Grapefruit and grapefruit juice should be avoided whilst taking pazopanib. Once daily. Treatment is continued until disease progression or unacceptable toxicity. Mildly emetogenic routine use of prophylactic antiemetics not required. Not applicable. FBC U+E LFT Calcium Magnesium Thyroid function Blood pressure ECG Urinalysis (for proteinuria) BP should be well controlled prior to initiation of pazopanib. Regular investigations FBC U+E Controlled document Document Number Version Number Page 1 of 5

2 Standard limits for administration to go ahead if blood results not within range, authorisation to administer must be given by prescriber/consultant LFT Calcium and Magnesium Thyroid function Blood pressure ECG Urinalysis Periodic monitoring as indicated Every 12 weeks Weekly for first cycle then every 4 weeks Periodic monitoring only if relevant cardiac history Periodic monitoring for proteinuria Neutrophil count >1.5 x 10 9 /L Platelet count >100 x 10 9 /L Creatinine clearance Bilirubin ALT/AST 30ml/min 2xULN 3xULN Dose modifications Haematological toxicity Use of pazopanib is not recommended where there is a significant risk of haemorrhage. Haemorrhage has been reported as a rare complication of pazopanib Renal impairment Hepatic Impairment (on initiation) Hepatic Impairment (during treatment) Myelosuppression may require dose (in steps of 200mg) and/or 1-2 week break in treatment until resolved to Grade 1. CrCl 30 ml/min 100% Pazopanib Dose <30 ml/min There is no experience of pazopanib in this patient population-use with caution following discussion with consultant. * *Pharmacokinetic studies suggest that renal impairment is unlikely to have a clinically relevant effect on pazopanib metabolism and clearance Bilirubin Pazopanib Dose 1.5 x ULN 800mg and closely monitor LFTs xuln 200mg and closely monitor LFTs >3 x ULN Contra-indicated Bilirubin AST/ALT Pazopanib Dose 2xULN 3xULN 100% 2xULN 3-8x ULN Continue on Pazopanib but monitor transaminases weekly until they return to 3xULN 2xULN >8xULN Hold Pazopanib until transaminases 3xULN. If benefit is deemed to outweigh risks of hepatoxicity, reintroduce at reduced dose and monitor LFTs weekly for 8 weeks. If, subsequent to this, AST ALT >3xULN, discontinue >2xULN AND >3x ULN Perform bilirubin fractionation. If direct (conjugated) bilirubin is > 35 % of total bilirubin, discontinue pazopanib.* *If bilirubin is > without ALT elevation, bilirubin fractionation should be performed. If bilirubin is <35% direct (conjugated), continue with Pazopanib. If bilirubin is >35% direct (conjugated), further evaluation for underlying cause of cholestasis should be performed. Controlled document Document Number Version Number Page 2 of 5

3 NCI Common toxicity criteria Toxicity Definition Dose adjustment Hypertension Diarrhoea Palmar-Plantar Erythrodyaesthesia (Hand-Foot Syndrome) Stomatitis Persistently high blood pressure >140/90mmHg despite standard antihypertensive therapy Grade 2: Increase of 4-6 stools per day over baseline; moderate increase in ostomy output compared to baseline Grade 3/4: Increase of 7 stools per day over baseline; incontinence; hospitalization indicated; severe increase in ostomy output compared to baseline Grade 1: Minimal skin changes or dermatitis (e.g., erythema, oedema, or hyperkeratosis) Discomfort but no pain; no interruption of ADL Grade 2: Skin changes (e.g., peeling, blisters, bleeding, oedema, or hyperkeratosis) Pain; limiting instrumental ADL Grade 3: Severe skin changes (e.g., peeling, blisters, bleeding, oedema, or hyperkeratosis) Pain; limiting self care ADL Grade 1: painless ulcers, erythema or mild soreness Grade 2: painful erythema, oedema, or ulcers but can eat or swallow Grade 3: painful erythema, oedema, or ulcers requiring IV hydration, and cannot eat Grade 4: severe ulceration or requires parenteral or enteral nutritional support or prophylactic intubation. Reduce dose in 200mg steps and continue to monitor. If hypertension persists, discontinue pazopanib. Delay until Grade 1 then resume at 100% Delay until Grade 1 then resume with 200mg dose Treat symptomatically and maintain doses at 100% 1 st appearance: delay until with 200mg dose 2 nd appearance: delay until with further 200mg dose 3 rd appearance: discontinue permanently 1 st appearance: delay until with 200mg-400mg dose 2 nd appearance: discontinue or delay until Grade 1 then resume with 200mg-400mg dose 100% Omit until toxicity Grade 1, then resume with 200mg dose Omit until toxicity Grade 1, then resume with mg dose Discontinue OR Omit until toxicity Grade 1, then resume with mg dose Controlled document Document Number Version Number Page 3 of 5

4 Adverse effects the contents of the table indicate the adverse effects that should be documented on consent to treatment forms Rare or serious side effects Myelosuppression, including neutropenia Gastrointestinal perforations and fistula Cardiotoxicity Teratogenicity QT prolongation and Torsade de pointes Haemorrhagic events Arterial thrombotic events: myocardial infarction, transient ischaemic attacks, ischaemic strokes Frequently occurring side effects Hypertension Delayed wound healing Diarrhoea Stomatitis Palmar-Plantar Erythrodyaesthesia (Hand-Foot Syndrome) Hypothyroidism Thrombocytopenia Anorexia Proteinuria Nausea and vomiting Other Significant drug interactions For full details consult product literature/reference texts Taste disturbances, skin and hair colour changes, fatigue Avoid co-administration of strong inhibitors of CYP3A4 (e.g. ketoconazole, voriconazole, clarithromycin, ritonavir) as these may increase plasma concentrations of pazopanib. Grapefruit and grapefruit juice should be avoided as they contain an inhibitor of CYP3A4 and may increase plasma concentrations of pazopanib. Avoid co-administration of strong inducers of CYP3A4 (e.g. rifampicin) as these may reduce exposure to pazopanib. Strong inhibitors and inducers of P-glycoprotein (P-gp) or breast cancer resistance protein (BCRP) should be avoided due to risk of altered exposure to pazopanib. Selection of alternative concomitant medicinal products with no or minimal potential to inhibit or induce P-gp or BCRP should be considered. Concomitant administration of pazopanib with uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1) substrates (e.g. irinotecan) should be undertaken with caution since pazopanib is an inhibitor of UGT1A1. Concomitant administration of pazopanib with human organic anion transporting polypeptide (OATP1B1) substrates such as rosuvastatin should be undertaken with caution since pazopanib is an inhibitor of OATP1B1. Cumulative Doses Not applicable. References National Institute of Health and Clinical Excellence Technology Appraisal 215. Pazopanib for the first line treatment of advanced renal cell carcinoma [internet] accessed 13/4/2011. Available at Summary of Product Characteristics Votrient (Pazopanib) 200mg and 400mg film coated tablets (GSK) [internet], accessed 13/4/2011,available at +and+400+mg+film+coated+tablets/ Controlled document Document Number Version Number Page 4 of 5

5 Study VEG108844, a Study of Pazopanib versus Sunitinib in the Treatment of Subjects with Locally Advanced and/or Metastatic Renal Cell Carcinoma (COMPARZ trial protocol, amendment number 2). 1 st April 209. NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [internet] accessed 04/02/2011 available at 14_QuickReference_5x7.pdf Document title Pazopanib for metastatic renal cell carcinoma Document number ASWCS11 UROL002 Approval date 16/06/2011 Written by Amit Bahl, Consultant Oncologist, BHOC Checked by James Carr, Network Pharmacist, ASWCS Authorised by Jeremy Braybrooke, Chair ASWCS Drugs and Therapeutics Committee Review date 16/06/2012 Document reviewed by Version number Summary of changes Version 1.1.a Controlled document Document Number Version Number Page 5 of 5