Carboplatin dosage: prospective evaluation of a simple formula based on renal function.
- Study type
- Other
- Design
- Retrospective pharmacokinetic analysis to derive the formula, followed by a prospective clinical and pharmacokinetic study to evaluate it
- Sample size
- 18 patients in the retrospective analysis; 31 patients (40 treatment courses) in the prospective study; 13 patients in the analysis of body surface area and non-renal clearance
- Source
- JCO · 1989
In plain words
Carboplatin is a chemotherapy drug, and the right amount for each patient depends on how well their kidneys work, because the drug leaves the body through the kidneys. In this study, a simple formula based on a kidney function test was built and tested to set the dose for each person. This method makes the amount of drug the body receives more predictable and helps keep effects on the blood counts at a manageable level.
Key results
Treatment arms and regimens
18 patients; the relationship between carboplatin plasma clearance and GFR was examined and a dosing formula was derived from it: dose (mg) = target AUC × (1.2 × GFR + 20). Dosing details in the full paper.
31 patients with 40 courses of carboplatin; the dose was set with the derived formula and the target AUC was escalated from 3 to 8 mg/mL/min. The formula was revised after this study: dose (mg) = target AUC × (GFR + 25). Details of other doses in the full paper.
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
In the retrospective analysis, 18 patients with a pretreatment glomerular filtration rate (GFR) of 33 to 136 mL/min were studied. In the prospective study, 31 patients with a GFR of 33 to 135 mL/min were treated with carboplatin. Both previously treated and untreated patients were included. The cancer types are not stated in the abstract.
Endpoints
Accuracy of the formula in predicting the observed AUC of free plasma carboplatin, the relationship between carboplatin clearance and GFR, haematological toxicity at different AUC levels, and the relationship between body surface area and non-renal clearance.
Safety and side effects
AUC values of 4 to 6 in previously treated patients and 6 to 8 mg/mL/min in untreated patients produced manageable haematological toxicity. Exact rates of grade ≥3 adverse events are not given in the abstract.
Clinical significance and place in guidelines
This paper introduced a simple formula for calculating the carboplatin dose from the GFR and the target AUC (dose = target AUC × (GFR + 25)), and according to the abstract it proposed target AUCs of 5 and 7 for single-agent use in previously treated and untreated patients, respectively. The abstract stresses that the target AUC must be redefined for combination chemotherapy. The formula's place in current guidelines and how widely it is used in practice should be checked in separate sources; the abstract gives no information on these points.
Limitations
According to the abstract, patient numbers were small (18 patients in the retrospective analysis and 31 in the prospective study). Cancer types and efficacy outcomes are not reported in the abstract. The validity of the formula depends on the assumption that body size has no effect on non-renal clearance (tested in 13 patients). The target AUC for combination chemotherapy must be redefined.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.