Betsi Cadwaladr University Health Version: 1.3 CSPM2 Hydration Protocol for Cisplatin Chemotherapy Date to be reviewed: July 2018 No of pages: 9 Author(s): Tracy Parry-Jones Author(s) title: Lead Cancer Services Pharmacist Responsible dept / Cancer and Clinical Services Division director: Approved by: Cancer & Haematology Medicines Management Group Date approved: 16.06.15 Endorsement by: Drugs and Therapeutics Committee Date endorsed: 01.07.15 Date activated (live): 01.08.15 Date EQIA completed: Documents to be read Chemotherapy regimen protocols alongside this policy: SPC for individual drugs Review Purpose of Issue/Description of current changes: First operational: Previously reviewed: Changes made yes/no: PROPRIETARY INFORMATION This document contains proprietary information belonging to the Betsi Cadwaladr University Health Board. Do not produce all or any part of this document without written permission from the BCUHB. BCUHB Version: 1 Page 1 of 15
Contents Introduction... 3 Prevention of cisplatin-induced nephrotoxicity... 3 Risk Factors... 4 Scope... 4 Assessment prior to chemotherapy... 4 Cisplatin Hydration Schedules... 5 Monitoring during chemotherapy... 6 Prior to discharge... 6 Dose modification for renal impairment... 7 IV Hydration for Cisplatin 2
CISPLATIN HYDRATION PROTOCOL Introduction Nephrotoxicity is a major dose-limiting side effect of Cisplatin. The kidney accumulates cisplatin to a greater degree than other organs and is the major route for its excretion. The cisplatin concentration in proximal tubular epithelial cells is about 5 times the serum concentration. The disproportionate accumulation of cisplatin in kidney tissue contributes to cisplatin-induced nephrotoxicity. Cisplatin nephrotoxicity can present in a number of ways including hypomagnesaemia, increased serum creatinine and urea. However, the most serious and one of the more common presentations is acute kidney injury (AKI) which occurs in 20 30% of patients. Typically, the onset of renal toxicity begins several days after the dose of cisplatin. The urine output is usually preserved and the urine may contain glucose and small amounts of protein. Recovery of renal function usually occurs over a period of 2 4 weeks, although progressive and permanent nephrotoxicity can result with successive treatment courses despite preventative measures. Prevention of cisplatin-induced nephrotoxicity Despite the recent advances in understanding the mechanism of cisplatin induced nephrotoxicity, prevention still relies on drug dosage decrease, specific measures of hydration, and active screening for renal abnormalities as part of the pre-chemotherapy assessment. Good hydration and urine output prevents retention of cisplatin in the kidneys and is essential for minimizing damage in the kidneys. Approximately 80% of cisplatin is excreted within 24 of dose, therefore hydration should continue for this period. Although many hydration regimens include the use of either mannitol or furosemide, there is no good evidence that diuretics provide any added benefit. Recently, a randomized trial demonstrated that sodium chloride 0.9% alone or with furosemide provides better renal protection than sodium chloride 0.9% plus mannitol. Cisplatin and magnesium affect the same sodium and water channels in the outer medulla. Cisplatin induces magnesium depletion, and magnesium deficiency itself may enhance cisplatin nephrotoxicity. Cisplatin treatment often produces extensive gastrointestinal side effects, which might lead to more magnesium depletion through anorexia and diarrhoea. Eventually, patients with these side effects may become more susceptible to the nephrotoxicity of cisplatin. IV Hydration for Cisplatin 3
Therefore, magnesium repletion may attenuate cisplatin-induced nephrotoxicity. Serum magnesium levels should be monitored in patients receiving cisplatin chemotherapy. Risk Factors Risk factors that make some patients more susceptible to cisplatin induced nephrotoxicity include: Higher Dose Increased Frequency Other nephrotoxic medicines e.g. NSAIDs, aminoglycosides High Cumulative dose Female sex Older age Smoking Hypoalbuminaemia Pre-existing renal insufficiency (limited data in humans) Patients with diabetes appear to have a decreased risk of cisplatin nephrotoxicity. Scope There is no standard fluid hydration schedule for cisplatin administration, and schedules vary significantly across the UK. Hydration schedules should take into account the following conditions for the patient ; adequate renal function, adequate hydration prior to administration of cisplatin, no contraindication to saline loading (e.g. uncompensated cardiac conditions), and ability to comply with recommended oral hydration protocol, or expectation that volume status can be maintained (e.g. with fluids via enteral feeding tube or IV). The purpose of this protocol is to standardize hydration schedules and administration of cisplatin chemotherapy across BCUHB. The hydration schedules are based on the available evidence and standard practice in other cancer centers across the UK. Assessment prior to chemotherapy Patients should drink 2 litres of fluid over the 24 prior to chemotherapy Weigh the patient on arrival Provide the patient with a jug of water and advise to drink plenty throughout the day Assess performance status of the patient Check FBC and U&E (magnesium and potassium) and albumin levels IV Hydration for Cisplatin 4
Patients with low magnesium levels (<0 7 mmol/l) should have an additional 1-2g magnesium sulphate added to the pre-hydration bag. If patients have low magnesium levels, they may require oral supplementation between cycles (e.g. magnesium aspartate sachets one twice a day; magnesium glycerophosphate 1g two or three times a day, or magnesium carbonate 1g two or three times a day. Patients with low potassium levels (hypokalaemia) should be reviewed by a clinician and supplementation prescribed as necessary. Calculate the creatinine clearance using the Cockroft - Gault formula Ensure urine output is > 100mLs/hour prior to cisplatin dose. If urine output is less seek advice from a clinician. Cisplatin Hydration Schedules The table below provides a guide for the hydration requirements for cisplatin administration based on the dose of cisplatin. Cisplatin dose Pre-Hydration Cisplatin Post-Hydration Total Fluid mg/m 2 Volume 80 with 20mmolKCL and 10mmol MgSO4 IV over 2 Cisplatin in infused over 2 with 20mmol KCL and 10mmol MgSO4 IV over 2 3000mL 61-79 with 20mmol KCL IV over 1 hour Cisplatin in infused over 2 with 20mmol KCL and 10mmol MgSO4 IV over 2 3000mL 41-60 500mL Sodium IV over 30 minutes Cisplatin in IV over 2 with 20mmol KCL and 10mmol MgSO4 IV over 2 2500mL IV Hydration for Cisplatin 5
40 500mLSodium IV over 30 minutes Cisplatin in 1000mL 0.9% Sodium Chloride IV over 1 hour Patient required to drink 500mL before discharge 2000mL NB If another drug is being given in the regimen e.g. Etoposide then this may be used as pre-hydration (Etoposide in ) Monitoring during chemotherapy Monitor urine output at regular intervals throughout chemotherapy At the end of IV fluids, weigh the patient and review fluid input and output Re-weigh the patient if they have gained >2kg, they should be prescribed furosemide 20mg orally and urine output monitored for a further 30 minutes. Furosemide usage may be appropriate in patients predisposed to cardiac failure from hydration. If there are any concerns then discuss with medical team prior to discharging the patient. Prior to discharge Ensure the patient is able to maintain good oral (or via PEG) fluid intake Patient should be advised to drink 2 litres (4 pints) of fluid in the 24 following chemotherapy Confirm patients understanding of the importance of fluid intake Advise patient to contact the hospital if unable to drink due to vomiting Provide patient with a patient information leaflet IV Hydration for Cisplatin 6
Dose modification for renal impairment Review toxicity of previous dose of cisplatin and take account of previous renal impairment when making decision about subsequent doses. GFR (ml/min) Dose 60 100% 45-59 75% <45 Consider carboplatin Cockroft - Gault formula Male patients 1.23 x (140 age) x weight (kg) Serum Creatinine (micromol/l) Female patients 1.04 x (140 age) x weight (kg) Serum Creatinine (micromol/l) References 1. Ronald P. Miller et al. Mechanisms of Cisplatin Nephrotoxicity Toxins 2010, 2, 2490-2518. 2. Vincent Launay -Vacher et al. Prevention of cisplatin nephrotoxicity: state of the art and recommendations from the European Society of Clinical Pharmacy Special Interest Group on Cancer Care. Cancer Chemother Pharmacol (2008) 61:903 909. IV Hydration for Cisplatin 7
3. XIN YAO et al. Cisplatin Nephrotoxicity: A Review. Am J Med Sci 2007; 334(2):115 124. 4. SPC Cisplatin 1 mg/ml Concentrate for Solution for Infusion. Accord Healthcare Limited. www.medicines.org.uk [accessed on the 3 rd March 2015] 5. North East Yorkshire and Humber Cancer Alliance. Policy for Cisplatin Hydration (2014) www.hyccn.nhs.uk [accessed on the 3rd March 2015] Members of the IV Hydration Task and Finish Group: Name Prof Nick Stuart Sr Beryl Roberts Dr Angel Garcia Dr Anna Mullard Tracy Parry-Jones Dr. Carey MacDonald-Smith Sr Julie Roberts Sue Woodfine Title Oncology Consultant, Cancer CPG Matron, Nurse Clinician Oncology Consultant, Cancer CPG Oncology Consultant, Cancer CPG Lead Cancer Services Pharmacist Oncologist, Cancer CPG Heulwen Day Unit Manager Chemotherapy Nurse Consultation has taken place with: IV Hydration for Cisplatin 8
Name Title Date Consulted Cancer CPG Medicines Management Group 24.4.15 Pharmacy & MM CPG Technical Services Lead 30.4.15 Pharmacy & MM CPG Cancer services pharmacists 30.4.15 Cancer CPG Consultant Oncologists 30.4.15 Cancer CPG Consultant Haematologists 30.4.15 Cancer CPG Acute Oncology Nurses 8.5.15 Cancer CPG Chemotherapy Nurses 27.4.15 Pharmacy & MM CPG Policies & PGD sub-group 29.6.15 IV Hydration for Cisplatin 9