Regimen: Gemcitabine & Carboplatin for NSCLC

Transcription

1 Regimen: Gemcitabine & Carboplatin for NSCLC ICD10 codes Codes pre-fixed with C34. Indications Regimen details First-line chemotherapy for advanced (stage IIIB/IV) non-small cell lung cancer (NICE CG121) Day Drug Dose Route 1 Carboplatin AUC 6 IV 1 & 8 Gemcitabine 1250mg/m 2 IV *Dose (mg) = target AUC x [GFR (ml/min) + 25] In patients with significant co-morbidities or PS>1, consider Carboplatin AUC 5 and Gemcitabine 1000mg/m 2. Generally the Cockcroft-Gault calculation can be used to calculate creatinine clearance. However, care should be taken if creatinine level is not felt to truly reflect renal function as in extremes of BSA or in debilitated patients. Creatinine clearance should be capped at 125ml/min for carboplatin dosing as recommended by the US FDA. Consider EDTA clearance. Administration Day 1 Administer Gemcitabine first in 250ml-500ml of sodium chloride 0.9% over 30 minutes. Carboplatin should be given in 250ml- 500ml glucose 5% over minutes minutes. Carboplatin may interact with aluminium to form a black precipitate. Needles, syringes, catheters or intravenous sets containing aluminium parts that may come into contact with carboplatin should not be used for preparation or administration of carboplatin. Day 8 Gemcitabine in ml sodium chloride 0.9% over 30 minutes. Frequency Patients should be observed closely for hypersensitivity reactions, particularly during the first and second infusions. Hypersensitivity reactions may occur within a few minutes following the initiation of the infusion of carboplatin. Facilities for the treatment of hypotension and bronchospasm must be available. If hypersensitivity reactions occur, minor symptoms such as flushing or localised cutaneous reactions do not require discontinuation of therapy. The infusion may be temporarily interrupted and when symptoms improve restarted at a slower infusion rate. Chlorphenamine 10mg IV may be administered. Severe reactions, such as hypotension, bronchospasm or generalised rash/erythema require immediate discontinuation of carboplatin and appropriate therapy. Every 21 days, with treatment on day 1 and day 8 for a maximum of 4 cycles Page 1 of 5

2 Extravasation Carboplatin is an irritant (Group 3) Gemcitabine is a neutral agent (Group 1) Premedication Emetogenicity Additional recommended supportive medication Pre- treatment evaluation Regular investigations Standard limits for administration to go ahead if blood results not within range, authorisation to administer must be given by prescriber/consultant Dose modifications Haematological toxicity Day 1 Day 8 Renal impairment Hepatic impairment Chlorphenamine 10mg IV and hydrocortisone 100mg IV may be given if there has been a reaction to a previous dose of carboplatin Day 1 has moderate-high emetic potential refer to local protocol Day 8 has moderate-low emetic potential refer to local protocol Loperamide 4mg po stat then 2mg prn if diarrhoea develops. Mouthwashes as per local policy. H 2 antagonist or proton pump inhibitor if required. Prophylactic antibiotics should be considered on days FBC LFT U&E (inc. SrCr, Ca & Mg) EDTA Baseline if significant/suspected renal dysfunction FBC Pre D1 results valid for 72 hours LFT Pre D1 results valid for 7 days U&E (inc. SrCr) Pre D1 results valid for 7 days Neutrophil count 1.0 x 10 9 /L Platelet count 100 x 10 9 /L Creatinine Clearance >30ml/min Bilirubin Neutrophil count (x 10 9 /L) <1.5x ULN Platelet Dose modification on count recovery count (x10 9 /L) Carboplatin Gemcitabine 1.0 AND % 100% OR Delay then 75% Delay then 75% <0.5 OR <50 Delay then 75% Delay then 75% 1.0 AND 100 N/A 100% OR N/A 75% <0.5 OR <50 N/A Omit If the calculated GFR falls by >10% from previous cycle, consider dose recalculation. If calculated GFR appears to improve the dose should not be increased unless a clear cause of renal function improvement is documented (e.g. treatment of urinary tract obstruction). GFR ml/min Carboplatin dose Gemcitabine dose 30 Use AUC as per protocol 100% <30 EDTA then use AUC as per protocol. Consider alternative non-nephrotoxic regimen. Consider dose reduction clinical decision 20 Contra-indicated Transient increases in liver enzymes have been seen in patients being treated with both carboplatin and gemcitabine although no dose reduction is usually required since AST elevations do not seem to cause dose limiting toxicities. If bilirubin > 27 µmol/l, initiate gemcitabine treatment with dose of 800 mg/m 2. NCI Common Toxicity Definition Dose adjustment Page 2 of 5

3 Toxicity Criteria Febrile neutropenia ANC <0.5 x 10 9 /L plus fever requiring IV antibiotics +/- hospitalisation Give a 20% reduction for all future doses of carboplatin and gemcitabine Toxicity Criteria Grade 2 (Except for nausea/vomiting and alopecia) 3 (Except for nausea/vomiting and alopecia) (see below for neurotoxicity) Dose adjustment 100% of both drugs Delay until recovery to baseline, then resume treatment at a reduced dose. Discuss with consultant Neurotoxicity Grade Platinum Dose Gemcitabine Dose % 100% 2 50% 100% 3 Omit 100% 4 Discontinue treatment Adverse effects the contents of the table indicate the adverse effects that should be documented on consent to treatment forms Rare but Serious Side Effects Infertility Hypersensitivity reactions Pulmonary fibrosis (very rare) Haemolytic Uraemic Syndrome* U & E disturbances (especially hyponatraemia, hypomagnesaemia, hypokalaemia & hypocalcaemia) Frequently occurring Side Effects Nausea and vomiting Myelosuppression Mucositis / stomatitis Diarrhoea or constipation Peripheral neuropathy Oedema & proteinuria Significant drug interactions For full details consult product literature/ reference texts Other Elevation of transaminases; mild alopecia; fatigue / asthenia *Gemcitabine should be discontinued at the first signs of any evidence of microangiopathic haemolytic anaemia, such as rapidly falling haemoglobin with concomitant thrombocytopenia, elevation of serum bilirubin, serum creatinine, blood urea nitrogen, or LDH. Renal failure may not be reversible with discontinuation of therapy and dialysis may be required. Warfarin/coumarin anticoagulants: increased or fluctuating anticoagulant effects. Avoid if possible: in the first instance, consider switching patient to a low molecular weight heparin during treatment or if the patient continues taking an oral anticoagulant monitor the INR at least once a week and adjust dose accordingly. Carboplatin only: Aminoglycoside antibiotics: increased risk of nephrotoxicity and ototoxicity Clozapine: increased risk of agranulocytosis, avoid concomitant use Diuretics: increased risk of nephrotoxicity and ototoxicity Page 3 of 5

4 Comments Cumulative Doses Nephrotoxic drugs: increased nephrotoxicity ; not recommended Phenytoin: carboplatin reduces absorption and efficacy of phenytoin None N/A References Rudd RM, Gower NH, Spiro SG, Eisen TG, Harper PG, Littler JA, et al. Gemcitabine plus carboplatin versus mitomycin, ifosfamide, and cisplatin in patients with stage IIIB or IV non-smallcell lung cancer: a phase III randomized study of the London Lung Cancer Group. J Clin Oncol 2005; 23 (1): Sederholm C, Hillerdal G, Lamberg K, Kölbeck K, Dufmats M, Westberg R, et al. Phase III Trial of Gemcitabine Plus Carboplatin Versus Single-Agent Gemcitabine in the Treatment of Locally Advanced or Metastatic Non-Small Cell Lung Cancer. The Swedish Lung Cancer Study Group. J Clin Oncol 2005; 23 (33): Aerts JG, Surmont V, van Klaveren RJ, Tan KY, Senan S, van Wijhe G, et al. A phase II study of induction therapy with carboplatin and gemcitabine among patients with locally advanced nonsmall cell lung cancer. J Thorac Oncol 2006; 1 (6): National Institute of Health and Clinical Excellence Guideline CG121. Lung Cancer. The diagnosis and treatment of lung cancer April 2011 [internet] Accessed online on 25/07/2012 available at Summary of Product Characteristics Carboplatin 10mg/ml Intravenous Infusion (Hospira) [internet] accessed 26/07/2012, available at Summary of Product Characteristics Gemzar (Gemcitabine) 200mg powder for solution for infusion, Gemzar (Gemcitabine) 1g powder for solution for infusion (Lilly) [internet]. accessed 25/07/2012 available from NCI Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 [internet] accessed 25/07/2012 available at 14_QuickReference_5x7.pdf A British Thoracic Oncology Group phase III trial of gemcitabine plus cisplatin at 80mg/m2 versus gemcitabine plus cisplatin at 50mg/m2 versus gemcitabine plus carboplatin AUC 6 in stage IIIB/IV non-small cell lung cancer (NSCLC). Version /02/07. Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in hepatic impairment [internet]. accessed 25/07/2012 available at %20Dosage%20adjustment%20for%20cytotoxics.doc Daniels S. North London Cancer Network. Dose adjustment for cytotoxics in renal impairment [internet]. accessed 25/07/2012 available at %20Dosage%20adjustment%20for%20cytotoxics.doc South East London Cancer Network. Gemcitabine and Carboplatin for NSCLC Protocol [internet] accessed 26/07/2012 available at Derby-Burton Local Cancer Network. Gemcitabine+Carboplatin for NSCLC Protocol [internet] accessed 26/07/2012 available at Page 4 of 5

5 Document title Carboplatin Gemcitabine chemotherapy for NSCLC Document number ASWCS12Lu004 Approval date 20/03/13 Written by Adam Dangoor, Consultant Medical Oncologist, BHOC Checked by Georgina Holmes, Pharmacist, UHBristol NHSFT Authorised by Jeremy Braybrooke, Chair ASWCS Network Chemotherapy Group Review date 20/03/15 Document reviewed by Version number 2 Summary of changes Version Page 5 of 5