Antineoplastic agent:Testicular and metastatic ovarian tumours Cervical tumours Lung carcinoma Bladder cancer
DOSE IN NORMAL RENAL FUNCTION
Single agent therapy: 50–120 mg/m 2 as a single dose every 3–4 weeks or 15–20 mg/m2 daily for 5 days every 3–4 weeksCombination therapy: 20 mg/m 2 and upward, every 3–4 weeks
<10           : See ‘Other Information’
DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES
CAPD                :Unknown dialysability. Dose as in GFR <10 mL/min
HD                     :Not dialysed. Dose as in GFR <10 mL/min
HDF/high flux   :Dialysed. Dose as in GFR
<10           : mL/min
CAV/VVHD      :Unknown dialysability. Dose as in GFR 10 to 20 mL/min
IMPORTANT DRUG INTERACTIONS
Potentially hazardous interactions with other drugsAminoglycosides: increased risk of nephrotoxicity and possibly ototoxicity with aminoglycosides, capreomycin, polymyxins or vancomycinAntipsychotics: avoid concomitant use with clozapine, increased risk of agranulocytosisCytotoxics: increased pulmonary toxicity with bleomycin and methotrexate
ADMINISTRATION
Reconstition
Water for injection to form a 1 mg/mL solution
Route
IV infusion
Rate of Administration
Over 6–8 hours
Comments
Pre-treatment hydration, with 1–2 litres of fluid infused for 8–12 hours prior to cisplatin dose, is recommended in order to initiate diuresis. The drug is then well diluted in 2 litres sodium chloride 0.9% or glucose-saline solutions to ensure hydration and maintain urine output. Adequate hydration must be maintained during the following 24 hours, with potassium and magnesium supplementation given as necessaryCisplatin solutions react with aluminium – do not use equipment containing aluminium
OTHER INFORMATION
Dose modification depends not only on the degree of renal dysfunction, but also on the intended dose and the therapeutic end-point. In general, any patient with a GFR<70 mL/min should be highlighted as ‘at risk’ from cisplatin renal toxicity. Kintzel PE, Dorr RT. Anticancer drug renal toxicity and elimination: dosing guidelines for altered renal function. Cancer Treat Rev. 1995; 21: 33–64GFR (mL/min) Dose<60 100%50–60 75%40–50 50%<40 AvoidBennett <50 100%10–50 75%
<10           : and
HD                     : 50%An alternative approach is to consider changing to carboplatin, which can be dosed specifically according to GFRNon-enzymatically transformed into multiple metabolites. Good uptake of cisplatin in the kidneys, liver and intestine. Distributes into third spaces such as ascites and pleural fluid. Elimination of intact drug and metabolites is via the urine. In the first 24 hrs 20–80% is excretedOtotoxicity, nephrotoxicity and myelosuppression reported. Check hearing, renal function and haematology before treatment and before each subsequent courseToxicity is also associated with cumulative doses of cisplatin Hypomagnesaemia, hypocalcaemia and hyperuricaemia observedThe addition of mannitol to the infusion may aid diuresis and protect the kidneys.