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Systemic Anti-Cancer Treatment Protocol
Carboplatin / Etoposide (Oral and IV regimens)
PROTOCOL REF: MPHACAETLU (Version No: 1.0)
Approved for use in Small cell lung cancer Small cell cancer – any origin
Dosage
Drug Dose Route Frequency Carboplatin AUC 5 x (GFR + 25) IV infusion Day 1 only
Etoposide phosphate 100mg/m2 IV Day 1 only
Etoposide 200mg/m2 PO in 2 divided doses Days 2 and 3 Alternatively IV Days 2 and 3 100mg/m2
Repeated every 3 weeks for up to 6 cycles
Calvert formula for Carboplatin dosage Carboplatin dose in mg = AUC x (creatinine clearance + 25) If estimated GFR is used the Wright formula must be used for creatinine clearance. Do not use Cockcroft and Gault formulae as it is less accurate.
Supportive Treatments Anti-emetic risk - Moderate Dexamethasone tablets, 4mg twice daily for 3 days Domperidone 10mg oral tablets, up to 3 times a day as required
Issue Date: October 2017 Review Date: October 2021 Page 1 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0
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Interactions Aminoglycosides e.g. gentamicin, vancomycin and diuretics Increased risk of nephrotoxicity and ototoxicity. Renal function should be well monitored and audiometric tests carried out as indicated. Phenytoin Carboplatin can cause a decrease in phenytoin serum levels. This may lead to reappearance of seizures and may require an increase of phenytoin dosages. Warfarin The effects of warfarin may be increased. Monitor INR closely.
Extravasation risk Carboplatin: Irritant Etoposide phosphate: Non vesicant Refer to the network guidance for the prevention and management of extravasation
Administration
Day Drug Dose Route Diluent and rate 1 Dexamethasone 8mg PO 30 mins before chemotherapy
Ondansetron 16mg PO 30 mins before chemotherapy
Carboplatin AUC 5 IV In 500mL glucose 5% over 30 to 60 minutes Etoposide phosphate 100mg/m2 IV In 100mL sodium chloride 0.9% infusion over 15 minutes 2 Etoposide capsules 200mg/m2 PO in 2 divided doses
3 Etoposide capsules 200mg/m2 PO in 2 divided doses
OR
Issue Date: October 2017 Review Date: October 2021 Page 2 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0
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For patients who are unable to swallow etoposide capsules
Day Drug Dose Route Diluent and rate 2 Etoposide phosphate 100mg/m2 IV In 100mL sodium chloride 0.9% infusion over 15 minutes 3 Etoposide phosphate 100mg/m2 IV In 100mL sodium chloride 0.9% infusion over 15 minutes
If etoposide phosphate is unavailable then switch to standard etoposide intravenous preparation, administered in 250mL to 1000mL of sodium chloride 0.9% (concentration dependent expiry) over 60 minutes.
Notes Carboplatin Facilities to treat anaphylaxis must be present when administering carboplatin. If a patient experiences an infusion-related reaction, give future does with pre-medication cover of IV chlorphenamine 10mg and IV hydrocortisone 100mg.
Risk of infusion related reaction may be increased with previous exposure to platinums
Etoposide Round oral etoposide doses to the nearest 50mg Swallow whole on an empty stomach or one hour before food
Main Toxicities Nausea, vomiting, myelosuppression (thrombocytopenia, anaemia and neutropenia), alopecia
Carboplatin – nephrotoxicity, ototoxicity, infusion related reactions, transient liver enzyme increase
Issue Date: October 2017 Review Date: October 2021 Page 3 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0
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Etoposide – mucositis, oesophagitis and stomatitis occur infrequently, hyper or hypotension – see below, fatigue, fever, bronchospasm, peripheral neuropathy
Investigations and treatment plan
Pre Cycle 1 Cycle 2 Cycle 3 Cycle 4 Ongoing Medical X X X Alternate cycles Assessment Nursing X X X X X Every cycle Assessment FBC X X X X X Every cycle U&E & LFT & X X X X X Every cycle Mg Mg and Ca x X x x x Every cycle Serum Cr X X X X X Every cycle CrCl (Wright) X X X X Every cycle CT scan X X At end of treatment Informed X Consent Repeat as ECG X clinically indicated Blood Repeat if clinically X pressure indicated Respiratory Rate and O2 X X X X X Every cycle sats PS recorded X X X X X Every cycle Toxicities X X X X X Every cycle documented Weight X X X X X Every cycle recorded Blood Repeat if clinically X Glucose indicated
Issue Date: October 2017 Review Date: October 2021 Page 4 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0
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Dose Modifications and Toxicity Management
Haematological Toxicity
Proceed on day 1 if- Plt ≥ 100 x 109/L ANC ≥ 1.0 x 109/L
Delay 1 week on day 1 if- Plt ≤ 99 x 109/L ANC ≤ 0.9 x 109/L
These haematological guidelines assume that patients are well with good performance status, that other acute toxicities have resolved and the patient has not had a previous episode of neutropenic sepsis.
Non Haematological Toxicity
Renal Carboplatin Measure serum creatinine every cycle and use the Wright Formula to calculate CrCl. Note limitations of Wright Formula for very high and low CrCl. Discuss with consultant if in doubt.Patients with creatinine clearance values of less than 60 ml/min are at greater risk to develop myelosuppression. Carboplatin is contraindicated if glomerular filtration rate is ≤ 20 ml/min. Do not give carboplatin and discuss with Oncologist
The optimal use of carboplatin in patients presenting with impaired renal function requires adequate dosage adjustments and frequent monitoring of both haematological nadirs and renal function.
Etoposide CrCl (mL/min) Etoposide Dose Above 50 100% 15 to 50 75% Below 15 50%
Issue Date: October 2017 Review Date: October 2021 Page 5 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0
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Hepatic Carboplatin- Transient increases in liver enzymes have been reported. Probably no dose reduction necessary.
Etoposide – conflicting information exists for reductions with etoposide, use table below but discuss with oncologist if in doubt
Bilirubin (μmol/L) AST/ALT Etoposide Dose
(units/L) 26 to 51 or 60 to 180 50% Above 51 or >180 Clinical decision
Infusion These can occur with carboplatin and rarely with etoposide. Hypotension related can occur if etoposide is administered too quickly – slower the infusion and reactions give subsequent infusions at the slower rate Hypertension and flushing can also occur – stop infusion, monitor; blood pressure usually reverts to normal after a few hours
References
Carboplatin Summary of Product Characteristics, Hospira UK Ltd, Warwickshire. 20/07/05. Available from www.medicines.org.uk/emc/medicine. last updated 09/06/2009. Etopophos 100mg Powder for Solution for Injection, Summary of Product Characteristics Bristol-Myers Squibb Pharmaceutical Limited.23/05/1996 Available from www.medicines.org.uk/emc/medicine. Last updated 17/02/2012. Dosage Adjustment for Cytotoxics in Hepatic Impairment. January 2009 UCLH - Dosage Adjustment for Cytotoxics in Hepatic Impairment (Version 3 - updated January 2009) Dosage Adjustment for Cytotoxics in Renal Impairment. January 2009 UCLH - Dosage Adjustment for Cytotoxics in Renal Impairment (Version 3 - updated January 2009) Dooly M, Poole S, Limitations of Wright Formula estimates of renal function, Ann Oncol (June 2005) 16(6) 989-990
Issue Date: October 2017 Review Date: October 2021 Page 6 of 6 Protocol reference: MPHACAETLU Author: Tara Callagy Authorised by: Dr Carles Escriu & DTC Version No: 1.0