A comparison of methods of calculation for estimating carboplatin AUC with a retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer. European Lung Cancer Working Party.
We retrospectively analysed the data obtained in a large randomised trial performed in 505 eligible patients with advanced non-small cell lung cancer. Its purpose had been to compare a combination of carboplatin (200 mg/m2) and cisplatin (60 mg/m2) with or without the addition of ifosfamide. The present retrospective analysis assessed two ways of dosing carboplatin: according to body surface area (mg/m2) or to the estimated targeted area under the concentration versus time curve (AUC). Two different methods were used in the latter calculation: the Calvert formula using the Cockroft approximation to evaluate the glomerular filtration rate and the Chatelut equation. There was an excellent linear correlation between them. With the Chatelut method, the calculated administered AUC were lower. Whichever method was used, carboplatin AUC was not significantly associated with antitumour response rate nor patient survival. A statistically significant increase in haematological toxicity, mainly thrombopenia, was observed with an increase in the AUC. This effect was observed whatever AUC variable was considered, i.e. total dosage at course one, total dosage during the first three chemotherapy courses or dose intensity during the first three courses. The effect remained highly significant after adjustment for treatment arm. We conclude that for a moderate carboplatin dose in non-small cell lung cancer, the therapeutic index could be improved if dosage is calculated according to the AUC.
Sculier
J P
JP
Department of Medicine, Institut Jules Bordet, Brussels, Belgium. 101473.1044@compuserve.com
Paesmans
M
M
Thiriaux
J
J
Lecomte
J
J
Bureau
G
G
Giner
V
V
Koumakis
G
G
Lafitte
J J
JJ
Berchier
M C
MC
Alexopoulos
C G
CG
Zacharias
C
C
Mommen
P
P
Ninane
V
V
Klastersky
J
J
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage / Q000493:pharmacokinetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D002945:Cisplatin / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
D016190:Carboplatin; D002945:Cisplatin; D007069:Ifosfamide