Cisplatin & Topotecan for cervical cancer

DRUG ADMINISTRATION SCHEDULE

Day Drug Daily Dose Route Diluent & Rate Sodium Chloride 0.9% 250/500ml Infusion Fast Running Ondansetron* 8 mg Oral /Slow bolus/15 min infusion Dexamethasone 8 mg Oral

2 50 ml Sodium Chloride TOPotecan 0.75 mg/m IV bolus 0.9% over 30 minutes Mg SO4 10mmol 1000ml 0.9% Sodium IV Infusion Day 1 KCl 20mmol Chloride over 2 hours Mannitol 20% 100mls IV Infusion 100mls over 30 minutes or or or or Via saline drip Furosemide 20mg IV bolus 1000ml 0.9% Sodium CISplatin 50 mg/m2 IV infusion Chloride over 2 hours Mg SO4 10mmol 1000ml 0.9% Sodium IV Infusion KCl 20mmol Chloride over 2 hours Sodium Chloride 0.9% 250/500ml Infusion Fast Running Day 2 Metoclopramide 10mg IV bolus 2 50 ml Sodium Chloride TOPotecan 0.75 mg/m IV bolus 0.9% over 30 minutes Sodium Chloride 0.9% 250/500ml Infusion Fast Running

Day 3 Metoclopramide 10mg IV bolus 50 ml Sodium Chloride TOPotecan 0.75 mg/m2 IV bolus 0.9% over 30 minutes *Ondansetron IV must be infused over 15minutes in patients over 65 years of age. Either Mannitol 20% or Furosemide can be used to ensure adequate urine flow

CYCLE LENGTH AND NUMBER OF DAYS 21-day cycle for up to 6 cycles

APPROVED INDICATIONS As a treatment option for women with recurrent or stage IVB cervical cancer only if they have not previously received cisplatin.

ELIGIBILITY CRITERIA ECOG performance status 0 to 2 Adequate renal function (GFR over 60 ml/min)

RECOMMENDED TAKE HOME MEDICATION Ondansetron 8mg twice daily for 2 days Dexamethasone 4mg twice daily for 1 day Metoclopramide 10mg three times daily as required Loperamide as required (4mg after first loose stool and 2mg every 2 hours, to a maximum of 16 (2mg) tablets in 24 hours. Cisplatin Topotecan protocol CRP18-GY019 v1 0 Page 1 of 4 Issue Date 22/08/2018 Expiry Date: 08/2021 Cisplatin & Topotecan for cervical cancer

Ciprofloxacin 250mg twice daily if diarrhoea lasts >24hrs (see administration notes) Suggested antiemetic regimen - may vary with local practice. See CINV policy for more details

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&Es, LFTs as required; GFR doubled checked using Wright formulae

ASSESSMENT OF RESPONSE Treatment response is monitored by serial CA125 measurement before each cycle of treatment, and additionally radiologically prior to starting topotecan 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 Check renal function before commencing platinum. Use EDTA or Wright to calculate GFR. GFR must be above 60 ml/min for cisplatin-based treatment. If GFR < 60 ml/min discuss with an Oncology Specialist. If the Cockcroft & Gault calculated clearance alters by >20%, an EDTA clearance should be repeated and modification of the chemotherapy dose may be required, Discuss with an Oncology Specialist.

Patients must be made aware of the risk of diarrhoea occurring during and after the administration of topotecan and at any time before the next cycle. Diarrhoea must be treated immediately with high dose Loperamide (4mg after first loose stool and 2mg every 2 hours, to a maximum of 16 (2mg) tablets in 24 hours. Hospitalise if condition not resolved within 48 hours. For diarrhoea lasting greater than 24 hours add ciprofloxacin 250mg BD. Note many units give patient a supply of loperamide and ciprofloxacin at the start of treatment.

EXTRAVASATION See NCA/Local Policy

TOXICITIES  Risk of hypersensitivity and anaphylaxis, particularly on first and second cycle, starting within a few minutes of administration  Bone marrow suppression; anaemia, neutropenia, thrombocytopenia  Diarrhoea – risk of severe delayed diarrhoea  Abdominal pain  Nausea and vomiting  Fatigue  Alopecia  Rash Cisplatin Topotecan protocol CRP18-GY019 v1 0 Page 2 of 4 Issue Date 22/08/2018 Expiry Date: 08/2021 Cisplatin & Topotecan for cervical cancer

 Neurotoxicity (ototoxicity)  Peripheral neuropathy  Nephrotoxicity due to cisplatin

DOSE MODIFICATION / TREATMENT DELAY Haematological Toxicity:  Delay 1 week if ANC <1.0 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: o For patients who experience severe neutropenia (neutrophil count < 0.5 x 109/l) or thrombocytopenia (PLT < 25 x 109/L) for 7 days or more, or severe neutropenia associated with fever or infection, or who have had treatment delayed due to neutropenia, the topotecan dose should be reduced by 20% (i.e. from 0.75mg/m2/day to 0.6 mg/m2/day, or subsequently down to 0.45 mg/m2/day if necessary).

Non- Haematological Toxicity: Diarrhoea For patients who experience Grade 3 or 4 diarrhoea, the dose of topotecan should be reduced by 0.15 mg/m2/day for subsequent courses. Patients with Grade 2 diarrhoea may need to follow the same dose modification guidelines.

Renal Function Cisplatin  Baseline EDTA required. GFR prior to treatment should be > 50ml/min  Serum creatinine should be checked before each cycle of treatment. If there is a > 25% increase compared to the baseline, then the EDTA must be repeated.  If renal function deteriorates the Cisplatin dose can be adjusted as follows:

GFR (EDTA or measured Cisplatin Dose Creatinine Clearance) ≥ 50 ml/min Full dose Consider reducing to same cisplatin dose in mg as value of GFR in 40 - 50 ml/min mL/min < 40 ml/min Omit cisplatin. Consider substituting for carboplatin

Conversely if a patient has a GFR < 50ml/min initially and there is improvement in serum creatinine the GFR should be rechecked with an EDTA clearance.

Patients with functional hearing loss should have cisplatin omitted. Carboplatin AUC 3-5 can be substituted but must be authorised by the SpR/Consultant. The change and reason must be clearly documented in the patient’s clinical notes.

Topotecan Dosing recommendations for patients receiving topotecan with CrCl < 60 ml/min have not been established however a dose reduction should be considered. Avoid in moderate to severe renal failure, e.g. CrCl < 20ml/min.

Hepatic impairment There is insufficient experience with the use of topotecan in patients with severely impaired hepatic

Cisplatin Topotecan protocol CRP18-GY019 v1 0 Page 3 of 4 Issue Date 22/08/2018 Expiry Date: 08/2021 Cisplatin & Topotecan for cervical cancer function (serum bilirubin > 150 µmol/L) due to cirrhosis. Topotecan is not recommended to be used in this patient group.

TREATMENT LOCATION Should be given at Cancer Centre only

REFERENCES: 1. Paton, F., Paulden, M., Saramago, P., Manca, A., Misso, K., Palmer, S. and Eastwood, A., 2010. Topotecan for the treatment of recurrent and stage IVB carcinoma of the cervix. Health Technol Assess, 14(s1), pp.55-62.

Document Control Document Title: Carboplatin & Topotecan for ovarian cancer Current Document No: CRP18 GY018 1.0 Version: 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 First draft Changes

Cisplatin Topotecan protocol CRP18-GY019 v1 0 Page 4 of 4 Issue Date 22/08/2018 Expiry Date: 08/2021