1545P - Carboplatin dosing with the Calvert formula for adult Japanese patients with renal insufficiency

Date 28 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Cancer in Special Situations
Presenter Tomoyo Oguri
Citation Annals of Oncology (2014) 25 (suppl_4): iv517-iv541. 10.1093/annonc/mdu356
Authors T. Oguri1, T. Shimokata1, I. Ito2, Y. Yasuda2, M. Nishiyama3, A. Hamada4, Y. Hasegawa5, Y. Ando1
  • 1Department Of Clinical Oncology And Chemotherapy, Nagoya University Hospital, 466-8550 - Nagoya/JP
  • 2Department Of Nephrology, Nagoya University Graduate School of Medicine, Nagoya/JP
  • 3Research Institute For Drug Discovery, School of Pharmacy, Kumamoto University, Kumamoto/JP
  • 4Division Of Clinical Pharmacology Group For Translational Research Support Core, National Cancer Center Research Institute, National Cancer Center Hospital, 104-0045 - Tokyo/JP
  • 5Respiratory Medicine, Nagoya University Graduate School of Medicine, Nagoya/JP

Abstract

Aim

Carboplatin dosing is usually calculated with the Calvert formula on the basis of the patient's glomerular filtration rate (GFR) to achieve the target area under the plasma drug concentration - time curve (AUC) for each patient: Dose(mg)= target AUC(mg/ml×min)×[GFR(ml/min)+ 25]. However, the practical application of the Calvert formula in adult Japanese patients with renal insufficiency has not been studied.

Methods

Between February 2011 and July 2013, 9 adult Japanese patients who had estimated GFR (eGFR) lower than 30 mL/min/1.73m2 or were on maintenance hemodialysis (HD) were studied for carboplatin pharmacokinetics after 1-hour infusion of the drug, which were combined with etoposide, gemcitabine, or paclitaxel in the treatment of their advanced cancers. The dosage of carboplatin was calculated with the Calvert formula, in which GFR was directly measured by inulin clearance or was assumed to be 0 in those requiring HD. HD was started 23 hours after the end of carboplatin infusion. Plasma concentrations of free platinum were measured with inductively coupled plasma-mass spectrometry.

Results

Although there was a good correlation between estimated (GFR+25) and measured carboplatin clearances, the estimated clearances were constantly higher than the measured (MPE±SE=41 ± 10%) among all the 7 patients with renal insufficiency (eGFR, median 22.4, range 14.8 - 26.6 mL/min/1.73m2; inulin clearance, median 21.4, range 7.8 - 31.4 mL/min) and the 2 hemodialysis patients. Actual AUC were 5.4, 5.7, 6.2, and 9.0 for 4 patients with the target AUC of 5; 5.7, 6.2, and 7.1 for 3 with the target AUC of 4; and 5.1 and 8.7 for the two HD patients with the target AUC of 5 in both. The pre-dialysis carboplatin clearances of the HD patients were 20.5 and 11.1 ml/min, suggesting that the constant value of 25 of the Calvert formula, which closely corresponded to the non-renal clearance, might be too high for adult Japanese patients, particularly when they have renal insufficiency.

Conclusions

For adult Japanese patients with renal insufficiency, even with the use of GFR exactly measured on the basis of inulin clearance, the Calvert formula inherently could cause carboplatin overdosing as a result of apparent overestimation of carboplatin clearance.

Disclosure

Y. Yasuda: endowed chair : MSD, Dainippon Sumitomo Pharma, Chugai Pharmaceutical Co. Ltd., Kowa Pharmaceutical Co. Ltd., Nippon Boehringer Ingelheim, Nihon Medi-Physics Co. Ltd. Research support: Pfizer adviser to drug development: Astellas pharma Inc.; Y. Ando: Research support: Nippon Kayaku Co., Ltd. and Yakult Pharmaceutical industry Co., Ltd. Honoraria(lecture fee): Nippon Kayaku Co., Ltd. and Bristol-Myers Squibb Company Honoraria(manuscript fee): Janssen Pharmaceutical K.K. All other authors have declared no conflicts of interest.