PURPOSE: The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children given in combination with cyclophosphamide and etoposide. PATIENTS AND METHODS: Carboplatin was administered as part of a multiagent chemotherapy regimen to 21 pediatric patients less than 5 years of age with newly diagnosed, malignant central nervous system tumors. Patients, received cyclophosphamide, 1.2 g/m2, on day 1 and carboplatin on day 2 followed by etoposide, 100 mg/m2, each day. Carboplatin doses were calculated to achieve a targeted area under the serum concentration versus time curve (TAUC) of 5, 6.5 or 8 mg/ml.min based on each patient's measured glomerular filtration rate (GFR). Carboplatin pharmacokinetic parameters were determined after course 1 and then after every third course of therapy. RESULTS: The median carboplatin clearance and GFR after course 1 were 118 and 98 ml/min per m2, respectively. Targeted doses based on measured GFR reliably achieved the TAUC for carboplatin. The median (range) carboplatin clearance for four children less than 1 year of age was 76 (66-84) ml/min per m2, significantly lower (P = 0.05) than the value of 131 (80-158) ml/min per m2 for children from 1 to 4 years of age. The mean carboplatin clearance declined by 23% in 12 patients studied from course 1 to course 4 of therapy. The decrease was greater than 20% (range 20-53%) in 7 of the 12 patients studied. CONCLUSION: Carboplatin clearance for children aged between 1 and 4 years at diagnosis is approximately 45% higher than previously reported for pediatric patients, but declines after four courses of therapy. For children less than 1 year of age, carboplatin clearance per square meter is approximately 40% lower than patients 1 to 4 years of age. There are corresponding differences in GFR that provide a plausible explanation for the age and therapy-related changes in carboplatin clearance. Toxicity was acceptable for patients treated at a TAUC of 6.5 mg/ml.min for carboplatin given with etoposide and cyclophosphamide. The average carboplatin dose required for this AUC was 767 mg/m2.
PURPOSE: The pharmacokinetic parameters and maximal tolerated systemic exposure were determined for carboplatin in young children given in combination with cyclophosphamide and etoposide. PATIENTS AND METHODS: Carboplatin was administered as part of a multiagent chemotherapy regimen to 21 pediatric patients less than 5 years of age with newly diagnosed, malignant central nervous system tumors. Patients, received cyclophosphamide, 1.2 g/m2, on day 1 and carboplatin on day 2 followed by etoposide, 100 mg/m2, each day. Carboplatin doses were calculated to achieve a targeted area under the serum concentration versus time curve (TAUC) of 5, 6.5 or 8 mg/ml.min based on each patient's measured glomerular filtration rate (GFR). Carboplatin pharmacokinetic parameters were determined after course 1 and then after every third course of therapy. RESULTS: The median carboplatin clearance and GFR after course 1 were 118 and 98 ml/min per m2, respectively. Targeted doses based on measured GFR reliably achieved the TAUC for carboplatin. The median (range) carboplatin clearance for four children less than 1 year of age was 76 (66-84) ml/min per m2, significantly lower (P = 0.05) than the value of 131 (80-158) ml/min per m2 for children from 1 to 4 years of age. The mean carboplatin clearance declined by 23% in 12 patients studied from course 1 to course 4 of therapy. The decrease was greater than 20% (range 20-53%) in 7 of the 12 patients studied. CONCLUSION:Carboplatin clearance for children aged between 1 and 4 years at diagnosis is approximately 45% higher than previously reported for pediatric patients, but declines after four courses of therapy. For children less than 1 year of age, carboplatin clearance per square meter is approximately 40% lower than patients 1 to 4 years of age. There are corresponding differences in GFR that provide a plausible explanation for the age and therapy-related changes in carboplatin clearance. Toxicity was acceptable for patients treated at a TAUC of 6.5 mg/ml.min for carboplatin given with etoposide and cyclophosphamide. The average carboplatin dose required for this AUC was 767 mg/m2.
Authors: Steven Allen; Matthew W Wilson; Amy Watkins; Catherine Billups; Ibrahim Qaddoumi; Barrett H Haik; Carlos Rodriguez-Galindo Journal: Pediatr Blood Cancer Date: 2010-07-15 Impact factor: 3.167
Authors: Jennifer M Atkinson; Anang A Shelat; Angel Montero Carcaboso; Tanya A Kranenburg; Leggy A Arnold; Nidal Boulos; Karen Wright; Robert A Johnson; Helen Poppleton; Kumarasamypet M Mohankumar; Clementine Féau; Timothy Phoenix; Paul Gibson; Liqin Zhu; Yiai Tong; Chris Eden; David W Ellison; Waldemar Priebe; Dimpy Koul; W K Alfred Yung; Amar Gajjar; Clinton F Stewart; R Kiplin Guy; Richard J Gilbertson Journal: Cancer Cell Date: 2011-09-13 Impact factor: 31.743