A comparison of methods of calculation for estimating carboplatin AUC witha retrospective pharmacokinetic-pharmacodynamic analysis in patients with advanced non-small cell lung cancer

We retrospectively analysed the data obtained in a large randomised trial p erformed in 505 eligible patients with advanced non-small cell lung cancer. Its purpose had been to compare a combination of carboplatin (200 mg/m(2)) and cisplatin (60 mg/m(2)) with or without the addition of ifosfamide. The present retrospective analysis assessed two ways of dosing carboplatin: ac cording to body surface area (mg/m(2)) or to the estimated targeted area un der the concentration versus time curve (AUC). Two different methods were u sed in the latter calculation: the Calvert formula using the Cockroft appro ximation to evaluate the glomerular filtration rate and the Chatelut equati on. There was an excellent linear correlation between them. With the Chatel ut method, the calculated administered AUC were lower. Whichever method was used, carboplatin AUC was not significantly associated with anti-tumour re sponse rate nor patient survival. A statistically significant increase in h aematological 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 chemot herapy courses or dose intensity during the first three courses. The effect remained highly significant after adjustment for treatment arm. We conclud e that for a moderate carboplatin dose in non-small cell lung cancer, the t herapeutic index could be improved if dosage is calculated according to the AUG. (C) 1999 Elsevier Science Ltd. All rights reserved.