Carboplatin dosing
Directly mGFR is the preferred kidney function value in the Calvert formula, especially in patients with either:
- Curative treatment intent
- Clinical situations where estimated kidney function may be unreliable for accurate therapeutic dosing such as
- eGFR > 125 mL/min/1.73 m2
- eGFR ≤ 45 mL/min/1.73 m2
- extremes of body size or muscle mass
- amputees
- paraplegics
In all other clinical situations, eGFR adjusted to an individual’s body surface area (BSA-adjusted eGFR) is a suitable alternative to directly mGFR for use in the Calvert formula
- BSA-adjusted eGFRCKD-EPI (mL/min) = [eGFRCKD-EPI (mL/min/1.73 m2) x BSA (m2)]/1.73
NOTE: BSA can be calculated using Mostellar or Dubois Dubois formulas
NOTE: if an eGFR value is reported as eGFR ≥ 90 mL/min/1.73 m2 then manual calculation using serum creatinine is required before adjusting result for BSA to then be used in the Calvert formula.
Recalculation of carboplatin doses at each cycle is unnecessary, except when baseline kidney function (e.g. eGFR) alters by > 20% or when there is a change in the clinical status of the patient.
Reduction of target AUC in kidney dysfunction is not recommended, as it may compromise clinical benefit.
Kidney function should not be capped at 125 mL/min for use in the Calvert formularrrrr.
Cisplatin dosing
For eGFR < 60 mL/min/1.73 m2, to ensure therapeutic dosing and reduce the risk of a further decline in kidney function from cisplatin-induced renal adverse events, directly mGFR is preferred for initial dosing, especially where either:
- cisplatin dose > 50 mg/m2
- eGFR is unreliable (e.g., extremes of body composition, amputees, paraplegia, conditions of skeletal muscle)
To minimise the risk of cisplatin-induced renal adverse events, adequate preventative and supportive care measures (as per local institutional policies) are advised for all patients receiving cisplatin. This includes maintaining adequate euvolemia, monitoring urine output through appropriate fluid hydration pre- and post-infusion, and preventing salt-wasting with magnesium and potassium supplementationrrr.
Methotrexate dosing
Directly mGFR is preferred to guide the initial dose adjustment of oral and intravenous methotrexate in kidney dysfunction. To ensure therapeutic dosing and to reduce the incidence of methotrexate-related adverse events, clinical consensus is that directly measured GFR is preferred for initial dosing especially where:
- eGFR is < 60 mL/min/1.73 m2
- methotrexate doses are ≥ 500 mg/m2
- eGFR may be unreliable in specific clinical circumstances (e.g., extremes of body composition, amputees, paraplegia, conditions of skeletal muscle).
In all patients, to minimise the risk of methotrexate-induced AKI, preventative measures are advised:
- Avoidance of concomitant administration of drugs that inhibit renal tubular secretion and/or have additive nephrotoxic potential (especially for 24 hours either side of methotrexate doses).
- Drainage off third-space effusions prior to treatment to prevent methotrexate distribution to these compartments and subsequent delay of elimination.
- Monitoring of kidney function before, during and after methotrexate administration to identify signs of kidney function deterioration.
In patients receiving high-dose methotrexate (≥ 500 mg/m2), additional supportive care measures are required to minimise the risk of methotrexate-induced AKI:
- Maintaining intravenous hydration, adequate urinary output, fluid balance and urinary alkalinisation (pH > 7) before, during and after methotrexate administration as per treatment protocol.
- Pharmacokinetically-guided calcium folinate (leucovorin) rescue, starting 24 – 36 hours post methotrexate infusion (as per treatment protocol) until plasma methotrexate concentrations are at least < 0.1 µmol/L by 72 hours.
- Monitoring of methotrexate plasma concentrations every 24 hours from the end of the methotrexate infusion, with prompt intervention (including consultation with clinical pharmacology) if plasma concentrations are elevated at 48 hours (as per nomogram) to avoid life-threatening toxicity. Interventions may include intensification of calcium folinate (leucovorin), glucarpidase and/or dialysis, but are dependent on the time since methotrexate infusion, kidney function and timely access to the intervention.