CARBOPLATIN & ETOPOSIDE (CE) for SCLC

DRUG ADMINISTRATION SCHEDULE Day Drug Dose Route Diluent & Rate Sodium Chloride 0.9% 250/500ml Infusion Fast Running Dexamethasone 8mg Oral Day Ondansetron 8mg Oral /Slow bolus/15 min infusion 1 500/250ml 5% Glucose Carboplatin AUC 5 IV Infusion over 30 to 60 Minutes 1000ml 0.9% Sodium Etoposide 120mg/m2 IV Infusion Chloride over 90 minutes Days Etoposide 100 mg Oral TWICE DAILY 2 & 3 *Ondansetron IV must be infused over 15 minutes in patients over 65 years of age.

DOSE FORM Oral Etoposide given as 100mg twice daily. Available as 50mg and 100mg capsules.

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.

CYCLE LENGTH AND NUMBER OF DAYS Administered on a 21-day cycle.

APPROVED INDICATIONS First line treatment for SCLC (This regimen is also suitable for treatment of other Small Cell Cancers such as Small Cell Bladder Cancer).

ELIGIABILITY CRITERIA: None noted

EXCLUSION CRITERIA: None noted

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 3 drug combination. RECOMMENDED TAKE HOME MEDICATION Ondansetron 8mgs twice daily for 2 days Dexamethasone 4mgs twice daily for 1 day Metoclopramide 10mg three times daily as required Suggested antiemetic regimen - may vary with local practice. See CINV policy for more details

carboplatin etoposide 3 weekly CRP09 L008 v2.2 Page 1 of 3 Issue Date 02.03.2018 Expiry Date: 03.03.2021 CARBOPLATIN & ETOPOSIDE (CE) for SCLC

INVESTIGATIONS / MONITORING REQUIRED Pre-treatment Full blood count, urea and electrolytes, liver function tests, baseline radiology (CXR/ CT). Repeat radiology after 2 cycles Check renal function before commencing platinum. Use EDTA or Wright formulae to calculate GFR.

Prior to each cycle FBC, U/E’s, LFT’s as required; GFR doubled checked using Wright formulae

ASSESSMENT OF RESPONSE Metastatic: Tumour size and patient symptomatic response

REVIEW BY CLINICIAN To be reviewed by either a Nurse, Pharmacist or Clinician before every cycle.

NURSE / PHARMACIST LED REVIEW On cycles where not seen by clinician.

EXTRAVASATION See NCA/Local Policy

TOXICITIES  Risk of hypersensitivity and anaphylaxis with platinum, starting within a few minutes of administration  Nausea and vomiting  Myelosuppression, particularly, thrombocytopenia, anaemia & neutropenia  Nephrotoxicity  Peripheral neuropathy  Dizziness during infusion  Oedema/peripheral oedema  Lethargy  Mild Alopecia  Constipation  Electrolyte disturbance  Otological symptoms; 8000 Hz conduction deafness  Alteration in LFT’s (infrequent and transient)

DOSE MODIFICATION / TREATMENT DELAYS Haematological Toxicity:

Haematological Toxicity Proceed on day 1 if: PLT ≥ 100 ANC ≥ 1.0

If Hb < 10 & patient symptomatic will need blood transfusion, but may proceed with chemotherapy as planned if performance status (PS) stable.

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Hepatic impairment Etoposide Bilirubin ALT Etoposide dose 1.5 – 2.5 x ULN Or 1.5 – 2.5 ULN 50% > 2.5 x ULN Or > 2.5 ULN Omit & discuss with consultant

Renal impairment Carboplatin If creatinine level increases by >20% from the result used to calculate GFR (or pre- treatment baseline if EDTA performed) discuss with consultant and consider repeating EDTA.

Etoposide CrCl (ml/min) Dose > 50 100% 15 – 50 75% < 15 50%

Other toxicity If PS deteriorates to 3 or 4 and on assessment patient is more symptomatic withhold treatment and discuss with Oncologist

TREATMENT LOCATION Can be given at Cancer Centre or Cancer Unit

REFERENCES: 1. Smith IE, Evans BD, Gore ME, et al. Carboplatin (Paraplatin; JM8) and etoposide (VP- 16) as first-line combination therapy for small-cell lung cancer. J Clin Oncol. 1987 Feb; 5(2): 185-9.

Document Control Document Title: CARBOPLATIN & ETOPOSIDE (CE) for SCLC Current Document No: CRP09 L008 Version: 2.2 Chris Beck Chemotherapy Pharmacist Date Reviewer: 02.03.18 Northern Cancer Alliance Approved: Steve Williamson Consultant Due for Approved by: 03.03.21 Pharmacist Northern Cancer Alliance Review Summary of 1.1 Reformatted from old NCN/CCA versions Changes 1.2 Expiry date fixed

1.3 Updated GFR dose calculations

1.4 Added ‘other small cell cancers’ to indications

2.0a Oral Etoposide dose clarified (100mg twice daily for 2 days)

2.1 Protocol reviewed and reissued, Antiemetic advice updated

2.2 Protocol reviewed, parameters updated.

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