The dose-normalized area under the plasma carboplatin concentration versus time curve (AUC) ranged from 3.1 to 9.6 mg/mL.min/400 mg/m2 and there was only a weak linear relationship between carboplatin dose and AUC (R2 = .31). An official website of the United States government. and transmitted securely. The 2 main methods used to assay the unbound species are flameless atomic absorption spectrophotometry and high performance liquid chromatography. Ford C, Spitzer G, Reilly W, Adkins D. A phase II study of repetitive cycles of dose-intense carboplatin plus paclitaxel chemotherapy and peripheral blood stem cells in metastatic breast cancer. There is a wealth of information regarding dosetoxicity and doseresponse relationships but very little information is available in the literature examining the relationship between toxicity and response (Gurney et al, 1993). Relationships between systemic exposure to carboplatin, described as the area under the concentration-time curve (AUC), and both toxicity and response have been described. Capping the GFR (or Clcr) at 125 mL/min, using an adjusted body weight for overweight or . New creatinine- and cystatin C-based equations to estimate GFR without race. Clipboard, Search History, and several other advanced features are temporarily unavailable. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the articles Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the articles Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. It should not be used for drug dosing or to estimate GFR. Calvert et al. Last Update2022-01-01 11:37:22. . The pharmacokinetics of carboplatin are adequately described by an open 2-compartment model with elimination from the central compartment. Carboplatin pharmacokinetics in children were best described in most patients (16 of 22) by a two-compartment model. The data presented in Fig. Please enter a valid weight. Madhu Mazumdar, Alex Smith, William P. Tong, Robert J. Motzer, Calvert's Formula for Dosing Carboplatin: Overview and Concerns of Applicability in High-Dose Setting , JNCI: Journal of the National Cancer Institute, Volume 92, Issue 17, 6 September 2000, Pages 14341436, https://doi.org/10.1093/jnci/92.17.1434. Kirsch M, Weisse C, Berent A, Clifford C, Leibman N, Wittenburg L, Solomon SB, Lamb K. A sequential Bayesian algorithm for dose individualisation of carboplatin. 3. Rounding is applied to the final result, no rounding is applied throughout the calculations. Male = 50 kg + (2.3 x (Height in inches - 60)) Female = 45.5 kg + (2.3 x (Height in inches - 60)) The ideal weight result is converted in both kg and lbs for convenience, where (1 kg = 2.20462262 lbs). This impact is equivalent to the benefit from the use of adjuvant chemotherapy in node negative breast cancer, or the addition of paclitaxel to the CAF regimen in node positive breast cancer. Furthermore they are expensive and possibly unsafe. This calculator calculates carboplatin doses via the Calvert formula with a target Area Under the Curve (AUC), using three options for kidney function: Directly Measured GFR (mGFR)*. However, due to the variation in drug handling, a proportion of patients will be relatively underdosed since they are more capable of eliminating the drug. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. official website and that any information you provide is encrypted 1989;7(11):1748-56, Cockcroft DW, Gault MH. Disclaimer: The Cancer Institute NSW does not warrant or represent that the Information is free from errors or omission. Body Surface Area (BSA) Adjusted eGFR CKD-EPI **. Carboplatin dosing Formula of Carboplatin AUC dose GFR for Male = ( ( (140-age) / serum creatinine) * 1) (weight (kg) / 72) GFR for Female = ( ( (140-age) / serum creatinine) * 0.85) (weight (kg) / 72) Carboplatin Dose = Target AUC * (GFR + 25) GFR = Glomerular filtration rate people found this article helpful. The possible significance of the underdosing is outlined in Table 3. HHS Vulnerability Disclosure, Help eGFR and BSAadjusted eGFR are calculated to the nearest whole number. Showing results for carboplatin. sharing sensitive information, make sure youre on a federal Rowinsky EK, Flood WA, Sartorius SE, Bowling KM, Ettinger DS. 2015 Jul;76(1):53-9. doi: 10.1007/s00280-015-2769-9. To calculate dose accurately drug elimination needs to be understood. The information provided is a guideline to standard practice and not a substitute for clinical judgement. Oxford University Press is a department of the University of Oxford. First, it is important to remember that the validity of the regression application depends on whether the study population and outcomes measured are truly comparable to those employed in the trial on which the original regression analysis was based. Federal government websites often end in .gov or .mil. Forty-five studies were found between 1989 through 1999. According to the external standard method to calculate the peak area, that is. Body-surface area as a basis for dosing of anticancer agents: science, myth, or habit? the display of certain parts of an article in other eReaders. RellingMVPuiCHSandlundJTRiveraGKHancockMLBoyettJMSchuetzEGEvansWE2000, Adverse effect of anticonvulsants on efficacy of chemotherapy for acute lymphoblastic leukaemia, SamsonMKRivkinSEJonesSECostanziJJLoBuglioAFStephensRLGehanEACummingsGD1984, Dose-response and dose-survival advantage for high versus low-dose cisplatin combined with vinblastine and bleomycin in disseminated testicular cancer. The variability of the predicted y as given in equation 7 with 2 replaced by AUCi2 2 will increase as higher AUC is targeted. Carboplatin can be fairly accurately dosed by measuring the GFR. Carboplatin is not always dosed on AUC and is commonly regimen-specific in regards to dosing by AUC, mg/m. It is also useful to predict the AUC and estimate the resultant toxicity in such patients. Phase I trial, including pharmacokinetic and pharmacodynamic correlations, of combination paclitaxel and carboplatin in patients with metastatic non-small-cell lung cancer. To see all protocols that comply with the WHO Essential Medicine List. This site needs JavaScript to work properly. As yet there are no useful in vivo measures of drug elimination that can be used for dose calculation. Chemotherapy plus atezolizumab for a patient with small cell lung cancer undergoing haemodialysis: a case report and review of literature. In other words, the impact of this violation is expected to be more severe for higher values of AUC. The .gov means its official. Carboplatin is an antineoplastic agent that interferes with DNA replication and cell division. This is applicable to patients who receive hemodialysis within 12-18 h after carboplatin infusion. The second and more serious flaw is rooted in the underlying assumption of linear regression theory. Cancer Chemother Pharmacol. Three studies from the 1970s and 80s purport a relationship between lack of myelosuppression and lack of anti-tumour effect in osteosarcoma and multiple myeloma (Cortes et al, 1974; McIntyre et al, 1978; Carpenter et al, 1982). Oguri T, Shimokata T, Ito I, Yasuda Y, Sassa N, Nishiyama M, Hamada A, Hasegawa Y, Ando Y. Until better dose calculation methods are determined most clinicians will continue with the traditional method using BSA. 1995 Dec;22(6 Suppl 15):34-7 More recently a number of limited sampling strategies have been proposed as well as Bayesian dose individualisation techniques. About this Carboplatin dose calculator. Adult. -, Ann Oncol. -, Cancer Chemother Pharmacol. A recent randomised study by the Australian Lymphoma and Leukaemia Group comparing high dose cyclophosphamide, epirubicin, vincristine and prednisolone (CEOP) with standard dose CEOP, showed that those patients who did not experience a nadir neutrophil count of <1.0109 per litre, had a statistically inferior progression free survival (Gurney et al, manuscript in preparation). mg/kg/dose or mcg/kg/dose. The guidelines allow a framework in which to work, in an area currently fraught with uncertainty. Carboplatin-based combination chemotherapy for testicular cancer: relationship among administration dose of carboplatin, renal function and myelosuppression. In our phase I study, the carboplatin dose was escalated with the use of AUCs of 12, 15, 18, 21, 24, 28, and 32 mg/mL per minute. The ePub format uses eBook readers, which have several "ease of reading" features Pilot study comparing serum chemotherapy levels after intra-arterial and intravenous administration in dogs with naturally occurring urinary tract tumors. -. It is unreasonable to use a small portion of an extra vial of chemotherapy if the dose prescribe is inaccurate 40% of the time. In this context, AUCi is not a part of the dependent random variable but is an independent random variable. Use is subject to eviQs disclaimer available at www.eviQ.org.au. used to calculate carboplatin dose, with the estimated GFR being obtained from Cockcroft-Gault equation, CKDEPI equation, and the Janowitz et al.'s equation. It is important that this relationship is examined more fully in other cancer types. Hiraike M, Hiraki Y, Misumi N, Hanada K, Tsuji Y, Kamimura H, Karube Y, Kashiwabara K. Cancer Chemother Pharmacol. Before Twelve rules for dose calculation of chemotherapy are given that can be used as a guideline until better dose-calculation methods become available. Guidelines exist for dose adjustment of other cytotoxic drugs that are predominantly renally excreted ( Kintzel and Dorr, 1995. The formula is simplified in the equation as: In stage II, the authors used this formula to dose 31 patients for target AUCs of 38 mg/mL per minute. Weigh yourself. Carboplatin dosing. and transmitted securely. currently, the carboplatin dose is very mild and uncommon, and hearing loss or neuropathy changes are rare. Carboplatin dose is based on the Calvert formula: Dosage = Target AUC x (GFR* + 25) *Where the GFR is provided by the eCrCl. Less is known about the variation in other critical hepatic elimination processes such as active biliary excretion by multidrug resistance gene 1 (MDR1), multidrug resistance-associated protein 2 (MRP2) and the other ATP binding cassette (ABC) family of efflux pumps, although some polymorphisms have been identified (Tanabe et al, 2001). Cancer Chemother Pharmacol. However, clinicians should be mindful of the inaccuracies of this system and should not be duped by its pseudo-scientific use of formulas and slide rules. M F . sharing sensitive information, make sure youre on a federal Learn more by registering for my course on noncompartmental analysis at https://www.udem. Now we know the GFR value of the patients using the target AUC which is around 7 mg/ml/min, we can find the dosage of the Carboplatin of the patient. Before already built in. Let's say the appropriate dosage of the active substance is 2 mg/kg of body weight. These patients will receive significantly lower or higher fixed doses. This approach does not satisfy the underlying assumptions of a linear model and could greatly affect prediction. -, Semin Oncol. Suzuki K, Matsumoto K, Hashimoto K, Kurokawa K, Jinbo S, Suzuki T, Imai K, Yamanaka H, Kawashima K, Takahashi H. Li S, Huang H, Liao H, Zhan J, Guo Y, Zou BY, Jiang WQ, Guan ZZ, Yang XQ. Refer to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for standard dosing recommendations based on regimen. 1916; 17:863-871. van Warmerdam LJ, Rodenhuis S, van der Wall E, Maes RA, Beijnen JH. The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25 (ml/min)]. 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