Comparison of two methods for carboplatin dosing in children with retinoblastoma

Background. Carboplatin is the most effective drug in retinoblastoma but systemic clearance is variable in young patients. While most regimens use a flat dose, individualized targeting may provide a more adjusted systemic exposure. Patients and Methods. We compared carboplatin doses between two groups of children with retinoblastoma that were treated using a flat dose of 560 mg/m² or a targeted AUC of 6.5 using a modified Calvert formula. Results. Ninety-eight patients with retinoblastoma received a total of 576 cycles of carboplatin (median 8 cycles). Fifty patients (51%) received a fixed dose per m², 32 (33%) received a dose based on AUC, 1 patient received fixed dose per kilogram, and in 15 patients a combination AUC and fixed doses was used. The median cumulative carboplatin dose (mg/m2) for patients who received eight cycles using fixed per m² dosing was 2151.8 (range, 1414.2-2852.0), compared to 1104.1 for nine patients who received eight cycles using Calvert dosing (range, 779.0-1992.7) (P<0.001). For cycles given using AUC, the median percentage of the hypothetical fixed per m² dose was 70% (range, 48-134%). Younger patients had larger differences. Patients receiving carboplatin based on fixed per m2 dosing were 3.0 times more likely to have a platelet transfusion (95% confidence interval, 1.3-7.3). Conclusions. Carboplatin administration needs to consider the changes in renal function occurring during the first months of life. The use of a targeted AUC provides the most accurate method; however, mg per kg of body weight dosing is a very reliable alternative method.