Evaluation of Calvert's Formula for Dosage Adjustment of Carboplatin in Japanese Patients with Hormone Refractory Prostate Cancer

Abstract

Carboplatin, an analogue of cisplatin, was introduced in 1981 and has proven effective against various malignancies. Carboplatin has less nonhematological toxicity such as renal failure than its parent compound cisplatin, 1) and thrombocytopenia is a dose-limiting factor of this drug.2) Since the 1990's, carboplatin in combination with paclitaxel has been used in the treatment of several solid tumors such as ovarian, breast and lung cancers. [3][4][5] At present, no chemotherapy is considered effective enough for prostate cancer, although regimens of mitoxantrone or taxanes was recently reported to be effective. 6) Especially, the combination therapy of carboplatin and paclitaxel has been regarded as valid for hormone refractory prostate carcinoma.7,8) Therefore, we used a regimen of paclitaxel and carboplatin every four weeks as performed in the treatment of other solid tumors, to prolong the life of patients with hormone refractory prostate cancer.Dosages of carboplatin are frequently determined based on Calvert's formula: dose (mg)ϭtarget AUCϫ(GFRϩ25), where AUC is the area under the concentration versus time curve (mg · min/ml) for free carboplatin, and GFR is the glomerular filtration rate (ml/min). 9) Since carboplatin is eliminated depending on glomerular filtration, 10) Calvert et al. 9) designed this simple formula to predict the AUC based on the glomerular filtration rate. The efficacy and toxicity of carboplatin were more closely related to AUC than dosage, 2) and to control the actual AUC of carboplatin into the target range is considered to be important. Although Calvert et al. 9) primarily measured the glomerular filtration rate using the [ 51 Cr]-EDTA method, creatinine clearance is generally used instead because of the inconvenience of measuring the glomerular filtration rate directly. Moreover, it is known that creatinine clearance is higher than the glomerular filtration rate, since creatinine is not only filtered by glomeruli but secreted by renal tubules. 11,12) Therefore, using creatinine clearance in place of the glomerular filtration rate may result in an overdose of carboplatin, and several studies have been done to examine the accuracy for prediction of carboplatin clearance, or to re-arrange the Calvert's formula for various types of tumors. [13][14][15][16] However, only a limited amount of information on the pharmacokinetics of carboplatin as well as efficacy of Calvert's formula is available in Japanese cancer patients. [17][18][19] In this study, we attempted the pharmacokinetic analysis of carboplatin, and evaluated the usefulness of Calvert's formula in prostate cancer patients treated with a combination therapy of paclitaxel and carboplatin. The relationships between the pharmacokinetics of carboplatin and clinical laboratory tests as well as toxicity were also evaluated. PATIENTS AND METHODS Patients and Chemotherapy RegimenTen patients with hormone refractory prostate carcinoma were enrolled in this study. All were inpatients at the Department of Urology, Kyoto Universi...

Determination of carboplatin in canine plasma by high‐performance liquid chromatography

“…This analytical procedure was validated in terms of selectivity specifi city, recovery, linearity, LLOQ, precision and accuracy. Our procedure eliminates the need for solid-phase extraction, nitrogen evaporation, ICP and MS (Sato et al, 2006;Falter and Wilken, 1999). Mass spectrometry and ICP are very expensive, require extensive training and are not readily available in veterinary hospitals for drug analysis.…”

“…A literature search revealed that there are several methods for quantifi cation of carboplatin in human plasma (Doz et al, 1998;Burns and Embree, 2000;Zufi a et al, 2001;Leger et al, 2002;Sato et al, 2006). Some of the methods involve post column derivatization, solid-phase extraction (Burns and Embree, 2000), ultrafi ltration and evaporation , the use of ICP-MS with nebulisation (Falter and Wilken 1999;Sato et al, 2006), LC-MS (Guo et al, 2003) and atomic absorption (Leger et al, 2002;Doz et al, 1998). However, appropriate methods for quantifi cation of carboplatin in dog plasma are scarce and high-tech instruments like LC-MS and ICP-MS are costly and not widely available in veterinary hospitals for drug quantitation.…”

A novel and fully validated hydrophilic interaction liquid chromatography with tandem mass spectrometry method for the determination of intact carboplatin in human plasma

“…In clinical practice, bone marrow suppression of carboplatin is not related to the administered dose but the area under the curve (AUC) of plasma concentration versus time of exposed . Similar relationships have been also studied between carboplatin AUC and antitumor effect . As carboplatin is mainly eliminated by the kidneys, the dose of carboplatin for a patient usually depends on his or her renal function .…”

“…As carboplatin is mainly eliminated by the kidneys, the dose of carboplatin for a patient usually depends on his or her renal function . To obtain therapeutic benefits or reduce adverse effect, therapeutic drug monitoring of carboplatin could be an effective tool to adjust dose of carboplatin for people with impaired renal function even those who receive hemodialysis . Therefore, determining the plasma target concentration of carboplatin and elucidating the variation in pharmacokinetics is required .…”