Chemotherapy Calculations

Introduction

The optimal cytotoxic drug dose should give a maximal antitumour effect with acceptable levels of toxicity.

  • Most chemotherapy is dosed using body surface area (BSA), except carboplatin, which is dosed using the Calvert formula.



Body Surface Area

The BSA formulas used most commonly are the Mosteller and Du Bois and Dubois equations.

The concept of BSA dosing arose from the need to convert drugs with a narrow therapeutic index from animal-sized doses used in preclinical trials to equivalent doses for human use in early clinical trials.

  • Surface area and weight-based dosing are also employed in an attempt to reduce interpatient systemic exposure of narrow therapeutic index drugs.
  • However, this established practice of using BSA does not necessarily predict pharmacokinetics or pharmacodynamics, and patient doses may often be adjusted based on haematology and other lab values.

Despite the known limitations, BSA remains the most common way of dosing chemotherapy today since there is a lack of any better alternative.

NOTE: Despite professional guidelines and a lack of supporting evidence, the practice of capping body surface area (BSA) at 2.0 m2 for chemotherapy dosing remains prevalent.



Carboplatin Calvert Formula

Initially, carboplatin dosing is also based on the body surface area, but it resulted in a variable degree of thrombocytopenia, with a number of patients requiring platelet transfusion.

Hence, Calvert formula becomes the adopted standard.

Total carboplatin dose (mg) = AUC target * (GFR + 25)

Few key points:

  • Typical target AUCs lies between 4 and 7, depending on the frequency of administration, previous treatment and the drugs being used in combination.
  • Currently, in Malaysia, the estimated GFR is still most commonly based on Cockcroft-Gault equation. In oversea settings, the Jelliffe formula is also commonly used. Both methods can underestimate or overestimate the GFR.
    • A 2017 study suggested that BSA-adjusted CKD-EPI is the most accurate published model to predict GFR.
    • An older study (2012) determined that the MDRD and CKD-EPI equations performed poorly compared with the reference standard radionuclide GFR; the Cockcroft-Gault equation showed smaller bias and higher accuracy in their oncology population.
  • Capping estimated GFR at a maximum of 125ml/min is recommended by FDA to avoid potential toxicities.
  • For patients with a GFR or CrCl less than 15 to 20ml/min, the use of Calvert formula is not recommended based on insufficient accuracy.
  • In obese patients, some clinicians prefer to use an adjusted body weight; the adjustment factor may vary based on practitioner and/or institutional preference.

NOTE: Carboplatin is more stable in dextrose 5% than normal saline (sodium chloride 0.9%). What is actually happening? Due to the presence of chloride ions in normal saline, carboplatin could be converted to cisplatin.



Summary

In clinical practice, the calculated cytotoxic drug doses are also frequently manipulated by rounding to the nearest convenient dose (commonly accepted within 5-10% of the calculated dose).



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