Relationship between calculated carboplatin area under the curve, using the Cockcroft-Calvert formula and the Chatelut formula, and thrombocytopenia induced by intraperitoneal carboplatin in combination with intravenous cyclophosphamide

Background. There is no standard formula to estimate doses for the intraperitoneal (IP) administration of carboplatin. We evaluated a combination of the Cockcroft and the Calvert (Cockcroft-Calvert) formula to determine the area under the curve (AUC) for IP carboplatin co-administered with intravenous (IV) cyclophosphamide (CPM). We also evaluated the correlation of carboplatin clearance determined by the Chatelut formula with carboplatin clearance determined by the Cockcroft-Calvert formula. Methods. We performed a retrospective study of the records of 149 treatments in 30 patients who received IP carboplatin and IV CPM for ovarian carcinoma. The glomerular filtration rate was calculated with the Cockcroft formula. Carboplatin doses were determined based on the body surface area. The Cockcroft-Calvert formula was used to calculate the AUC. The Chatelut formula was also used to calculate the clearance of carboplatin and the AUC. Results. The AUC calculated with the Cockcroft-Calvert formula was well correlated to the AUC calculated with the Chatelut formula (r^sup 2^ = 0.965). During the first four courses of IP carboplatin combined with IV CPM (300-500mg/m^sup 2^), the correlation between the percent decrease in platelet count and the calculated carboplatin AUC varied among methods: Cockcroft-Calvert formula AUC:r^sup 2^ = 0.460; Chatelut formula AUC:r^sup 2^ = 0.431; body surface area dose:r^sup 2^ = 0.204; total dose:r^sup 2^ = 0.143. Conclusion. To decrease patient platelet count by 67%, the optimal target AUC following IP administration of carboplatin in combination with 300-500mgCPM/m^sup 2^IV was calculated as 6.5, using the Cockcroft-Calvert formula, and as 7.5, using the Chatelut formula. Considerable modification of the IP carboplatin dose is required after the fourth course. A prospective study is ongoing to confirm these results.[PUBLICATION ABSTRACT]