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Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx )

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Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx ) Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx®) DRUG ADMINISTRATION SCHEDULE Day Drug Dose Route Diluent Rate Fast 5% Glucose 250/500ml Infusion Running Dexamethasone 8mg Oral Ondansetron* 8mg Oral /Slow bolus/15 min infusion Day 1 Liposomal 250ml 30 mg/m2 Infusion See below DOXOrubicin (Caelyx®) 5% Glucose 250ml CARBOplatin AUC 5 IV infusion 30 mins 5% Glucose *Ondansetron IV must be infused over 15 minutes in patients over 65 years of age. CARBOPLATIN DOSAGE: Dose (mg) = AUC x (GFR + 25) Where the GFR is the non-corrected EDTA clearance. If estimated GFR is undertaken the Wright formula must be used with AUC 5. Cockcroft & Gault formula is less accurate. INFUSION RATE The first dose of Caelyx® is administered at a rate no greater than 1 mg/minute. If no infusion reaction is observed, subsequent Caelyx® infusions may be administered over a 60-minute period. CYCLE LENGTH AND NUMBER OF DAYS Every four weeks until disease progression APPROVED INDICATIONS Second-line (or subsequent) treatment of patients with partially platinum-sensitive, platinum- resistant or platinum-refractory advanced ovarian cancer. ELIGIBILITY CRITERIA ECOG performance status 0 to 2 EXCLUSION CRITERIA In patients who have severe bone marrow depression and/or severe renal or severe hepatic impairment PREMEDICATION Antiemetic cover with neurokinin 1 (NK1) receptor antagonists ASCO 2017 antiemetic guidance recommends regimens containing carboplatin ≥ AUC4 should be classified as high risk of CINV and patients offered a three-drug combination of a neurokinin 1 (NK1) receptor antagonist, a serotonin (5-HT3) receptor antagonist and dexamethasone. Current practice in NCA is to start with a two-drug regimen serotonin (5-HT3) receptor antagonist and dexamethasone and add in a neurokinin 1 (NK1) receptor antagonist if CINV not adequately controlled. However, if pre-assessment of patient identifies risk factors for CINV, units may wish to start with a 3-drug combination. Carboplatin+Caelyx-Pegylated-Lipo-Doxorubicin-protocol-CRP09-GY020 v1 0 Page 1 of 4 Issue Date 22/08/2018 Expiry Date:22 /08/2021 Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx®) RECOMMENDED TAKE HOME MEDICATION Ondansetron 8mg twice daily for 2 days Dexamethasone 4mg twice daily for 1 days Metoclopramide 10mg three times daily as required Suggested antiemetic regimen - may vary with local practice. See CINV policy for more details INVESTIGATIONS / MONITORING REQUIRED ECG prior to commencement of treatment and as indicated thereafter. ECHO/MUGA scan pre-treatment and on alternate cycles if significant cardiac history, or previous anthracycline therapy. FBC, U&Es, LFTs and tumour markers as appropriate prior to each cycle. ASSESSMENT OF RESPONSE Treatment response is monitored by serial CA125 measurement before each cycle of treatment, and additionally radiologically prior to starting Caelyx® and after 3 cycles of treatment REVIEW BY CLINICIAN Every other cycle NURSE / PHARMACIST LED REVIEW On cycles where not seen by clinician. ADMINISTRATION NOTES Patient needs Glomerular Filtration Rate (GFR) prior to commencement of treatment for calculation of Carboplatin dosage. Subsequent measurement of GFR only needed if serum creatinine changes by >20% from initial measurement. Facilities to treat anaphylaxis MUST be present when the chemotherapy is given. Seek advice if the total lifetime dose of Doxorubicin will exceed 450 mg/m2 due to increased risk of cardiotoxicity. If the patient experiences early symptoms or signs of infusion reaction or minor hypersensitivity e.g. reactions, flushing, localised rash, immediately stop the infusion, give appropriate premedication (antihistamine and/or short acting corticosteroid) and restart at a slower rate. Units administering Caelyx® must have facilities available for the treatment of anaphylaxis and resuscitation. It is recommended that the Caelyx® infusion line be connected through the side port of an intravenous infusion of 5 % glucose. Do not use with in-line filters. EXTRAVASATION See NCA/Local Policy TOXICITIES Risk of hypersensitivity and anaphylaxis, particularly on first cycle Myelosuppression Nausea and vomiting Palmar/Plantar erythrodysaesthesia (hand-foot syndrome) Stomatitis / Mucositis Discoloured urine Cardiotoxicity Carboplatin+Caelyx-Pegylated-Lipo-Doxorubicin-protocol-CRP09-GY020 v1 0 Page 2 of 4 Issue Date 22/08/2018 Expiry Date:22 /08/2021 Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx®) Alopecia Nephrotoxicity Peripheral neuropathy Otological impairment, especially at 8000 Hz TREATMENT LOCATION Should be given at Cancer Centre only DOSE MODIFICATION / TREATMENT DELAY Haematological Toxicity: Delay 1 week if ANC <1.0 or Platelets <100 No dose modification for CTC grade I/II ANC Grade III/IV ANC → delay chemotherapy until recovered, if decide to continue dose as below: GRADE ANC PLATELETS MODIFICATION Wait until ANC ≥ 1.0 and platelets ≥ 100; resume Grade ≤ 3 ≥ 0.5 ≥ 25 with no dose reduction. Wait until ANC ≥ 1.0 and platelets ≥ 100; decrease Grade 4 < 0.5 < 25 dose by 25% Non-Haematological Toxicity: Week after prior Caelyx® dose Grade Adverse event Weeks 4 & 5 Week 6 Palmar-Plantar Erythrodysesthesia (PPE) Mild erythema, swelling, or Re-dose unless patient has Decrease Caelyx® dose by 25%; 1 desquamation not interfering with experienced a previous Grade 3/4 skin return to 4-week interval daily activities toxicity, in which case wait extra week erythema, desquamation, or Decrease Caelyx® dose by 25%; 2 swelling, not precluding normal Delay one week return to 4-week interval physical activities; blistering, ulceration, or swelling interfering with walking or normal 3 Delay one week Discontinue Caelyx® daily activities; cannot wear clothing Diffuse, causing infectious 4 complications, or a bedridden Delay one week Discontinue Caelyx® state/hospitalization Stomatitis Re-dose unless patient has painful ulcers, erythema or mild Decrease Caelyx® dose by 25%; 1 experienced a previous Grade 3/ 4 skin soreness or discontinue toxicity, in which case wait extra week painful erythema, oedema or ulcers Decrease Caelyx® dose by 25%; 2 Delay one week but can eat or discontinue painful erythema, oedema or ulcers 3 Delay one week Discontinue Caelyx® but cannot eat requires parenteral or enteral 4 Delay one week Discontinue Caelyx® support Renal impairment No data is available for Caelyx® with creatinine clearance < 30ml/min. Carboplatin+Caelyx-Pegylated-Lipo-Doxorubicin-protocol-CRP09-GY020 v1 0 Page 3 of 4 Issue Date 22/08/2018 Expiry Date:22 /08/2021 Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx®) Hepatic impairment Total Bilirubin (micromol/L) Caelyx® Dose < 21 100% 21-51 75% > 51 50% If first dose is tolerated without further increases in bilirubin and/or liver enzymes, subsequent doses may be increased by one dosage level as clinically indicated. No modification is required for carboplatin. REFERENCES: 1. National Institute for Health and Clinical Excellence. Technology Appraisal 389. Topotecan, pegylated liposomal doxorubicin hydrochloride, paclitaxel, trabectedin and gemcitabine for treating recurrent ovarian cancer. https://www.nice.org.uk/guidance/ta389 2. Pujade-Lauraine E, Uwe Wagner U, Aavall-Lundqvist E, Gebski V, Heywood M, Vasey PA, et al. Pegylated Liposomal Doxorubicin and Carboplatin Compared With Paclitaxel and Carboplatin for Patients With Platinum-Sensitive Ovarian Cancer in Late Relapse. J Clin Oncol 2010 28(20): 3323-3329 3. Summary of Product Characteristics – Caelyx 2mg/ml concentrate for solution for infusion, Janssen-Cilag Ltd, Last updated 20 Jan 2017, https://www.medicines.org.uk/emc/product/1462 Document Control Document Title: Carboplatin & Pegylated Liposomal Doxorubicin (Caelyx®) Document No: CRP09 GY020 Current Version: 1.0 Chris Beck, Author: Date Approved: 22/08/2018 Cancer Alliance Pharmacist Steve Williamson, Consultant Pharmacist, Approved by: Due for Review: 22/08/2021 Northern Cancer Alliance Summary of 1.0 Draft protocol created Changes Carboplatin+Caelyx-Pegylated-Lipo-Doxorubicin-protocol-CRP09-GY020 v1 0 Page 4 of 4 Issue Date 22/08/2018 Expiry Date:22 /08/2021 .
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