Department of Oncology, St. Jude Children's Research Hospital, Memphis, Tennessee, USA.
Pediatr Blood Cancer. 2010 Jul 15;55(1):47-54. doi: 10.1002/pbc.22467.
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.
We compared carboplatin doses between two groups of children with retinoblastoma that were treated using a flat dose of 560 mg/m(2) or a targeted AUC of 6.5 using a modified Calvert formula.
Ninety-eight patients with retinoblastoma received a total of 576 cycles of carboplatin (median 8 cycles). Fifty patients (51%) received a fixed dose per m(2), 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/m(2)) for patients who received eight cycles using fixed per m(2) 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 m(2) dose was 70% (range, 48-134%). Younger patients had larger differences. Patients receiving carboplatin based on fixed per m(2) dosing were 3.0 times more likely to have a platelet transfusion (95% confidence interval, 1.3-7.3).
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.
卡铂是治疗视网膜母细胞瘤最有效的药物,但在年轻患者中,其全身清除率存在差异。虽然大多数方案采用固定剂量,但靶向 AUC 可能提供更调整的全身暴露量。
我们比较了两组接受视网膜母细胞瘤治疗的儿童的卡铂剂量,一组采用 560mg/m2 的固定剂量,另一组采用改良的 Calvert 公式靶向 AUC 为 6.5。
98 例视网膜母细胞瘤患者共接受 576 个周期的卡铂治疗(中位数 8 个周期)。50 例(51%)患者接受每平方米固定剂量,32 例(33%)患者接受基于 AUC 的剂量,1 例患者接受固定剂量/千克,15 例患者采用 AUC 和固定剂量联合。接受每平方米固定剂量 8 个周期的患者的中位累积卡铂剂量(mg/m2)为 2151.8(范围,1414.2-2852.0),而接受 Calvert 剂量 8 个周期的 9 例患者的中位累积卡铂剂量为 1104.1(范围,779.0-1992.7)(P<0.001)。对于 AUC 周期,假设每平方米固定剂量的中位数百分比为 70%(范围,48-134%)。年龄较小的患者差异更大。接受基于每平方米固定剂量卡铂治疗的患者发生血小板输注的可能性是接受 AUC 治疗的患者的 3.0 倍(95%置信区间,1.3-7.3)。
卡铂给药需要考虑到生命最初几个月肾功能的变化。使用靶向 AUC 提供了最准确的方法;然而,按体重/kg 剂量给药是一种非常可靠的替代方法。