- Email: [email protected]
Survey of carboplatin dosing strategies in oncology practices
Research Notes
Survey of carboplatin dosing strategies in oncology practices Patrick Blankenship and J. Aubrey Waddell
Abstract Objectives: To identify variations in carboplatin dose calculations at oncology institutions and practices in the southeastern United States. Methods: 500 surveys were mailed to oncology practices in the southeastern United States to assess variations in carboplatin doses. The survey sought to determine assumptions that are made regarding carboplatin calculations and if different carboplatin doses result when participants are given the same data and patient characteristics. Results: The survey had a response rate of 12% (n = 56 of 467). The majority of responses used actual serum creatinine and actual body weight. The Cockcroft-Gault creatinine clearance formula was used most commonly. The doses calculated in the case example of an AUC (area under the curve) 6 dose of carboplatin ranged from 110 to 1,811 mg (mean 987 mg, median 963 mg). We determined a correct dose of 721 mg for the case example. Conclusion: The majority of responses to the case example indicated overdosing of carboplatin. Participants provided inconsistent doses, and their interpretation of the variables in the equations varied. More research is needed, and efforts should be made to have a universal modified Calvert formula with standardized assumptions to achieve consistent dosing across practices. Keywords: Area under the curve, carboplatin dosing, carboplatin equations. J Am Pharm Assoc. 2013;53:420–422. doi: 10.1331/JAPhA.2013.12053
C
arboplatin is a broad-spectrum antineoplastic agent used to treat a variety of neoplasms. During the 1980s, carboplatin was primarily dosed using the body surface area (BSA) method. However, since 1989, the area under the curve (AUC) method has predominantly replaced the BSA method as the basis for dosing carboplatin.1,2 The AUC methods most commonly used are the Calvert formula (CF) or one of the modified Calvert formulae (MCFs).1 Nearly three-quarters of an intravenous carboplatin dose is excreted unchanged in the urine. The elimination of carboplatin correlates with glomerular filtration rate (GFR). Calvert et al.2 developed a formula that would decrease doses with poor renal function and increase doses for higher-than-normal renal function. Also, CF helped predict carboplatin-associated toxicities such as thrombocytopenia and leucopenia.1 A radiopharmaceutical method (51Cr-EDTA clearance) was used to accurately determine GFR, as displayed in the original CF equation1: dose = AUC(GFR + 25). However, this method of measuring GFR was not widely used, probably as a result of the expense of radiopharmaceuticals, nonavailability of 51Cr-EDTA in the United States, and inconvenience of the time needed to measure GFR.3 The original CF was modified to substitute the 24-hour creatinine clearance (CrCl) for the radiopharmaceutically determined GFR1: AUC([24-hour CrCl] + 25). This substitution for GFR correlated reasonably well with the original CF, but this determination of renal function also is inconvenient.1 The most convenient and economical method is an estimation of CrCl instead of the approximation measurement. Examples of these MCFs include the Jelliffe formula substituted for GFR, the Cockcroft-Gault formula substituted for GFR, and Received March 7, 2012, and in revised form November 30, 2012. Accepted for publication December 1, 2012. Patrick Blankenship, PharmD, BCPS, is Clinical Pharmacist, Emergency Department, Blount Memorial Hospital, Maryville, TN. J. Aubrey Waddell, PharmD, FAPhA, BCOP, is Professor, College of Pharmacy, University of Tennessee, Knoxville, and Oncology Pharmacist, Blount Memorial Hospital, Maryville, TN. Correspondence: Patrick Blankenship, PharmD, BCPS, Blount Memorial Hospital, 907 East Lamar Alexander Pkwy., Maryville, TN 37804. Fax: 865-981-2258. E-mail: [email protected] Disclosure: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Acknowledgments: To Sheila Sands for administrative support. Previous presentation: American Pharmacist Association Annual Meeting & Exposition, March, 12–15, 2010, Washington, DC.
420 JAPhA | 5 3:4 | JUL /AUG 2013
ja p h a .org
Journal of the American Pharmacists Association
Research Notes
the Jelliffe formula (adjusted for BSA) substituted for GFR.1 Various equations are used to estimate GFR; therefore, a potential exists for variation in carboplatin doses.1 In addition, the assumptions and variables in the equations can cause variability in doses. These assumptions include the body weight value that is used (e.g., ideal body weight, adjusted body weight, actual body weight).1 Opinions also may differ regarding serum creatinine (SCr) when the level is lower than normal (e.g., rounding SCr to 0.8 or 1 mg/dL or using actual SCr).1 These concerns have not been evaluated in the literature extensively or addressed in large clinical trials.1
Objective We sought to identify variations in carboplatin dose calculations at oncology institutions and practices in the southeastern United States.
Methods To assess how carboplatin doses were determined, a survey (Appendix 1 in the electronic version of this article, available online at www.japha.org) was distributed by mail to oncology practices and hospitals in the southeastern United States in February to March 2010. The survey contained seven questions, including six multiple-choice questions and one case example question in which participants used given variables to determine or calculate a carboplatin dose. The survey was validated through five local oncology offices for reliability and validity. A public website was used to find the mailing addresses of U.S. oncology practices and centers in the southeastern United States. A total of 500 surveys were mailed with prepaid postage envelopes for returning completed surveys. The participants were given the option to return surveys via facsimile. Institutional review board approval was obtained from the Blount Memorial Hospital and University of Tennessee Health Science Center.
Results Of the 500 mailed surveys, 33 (6.6%) were nondeliverable because of incorrect addresses. A total of 56 (12%) of the remaining 467 surveys were returned. Two of the returned surveys were incomplete due to formulary issues, and one was inadvertently sent to a radiation oncology office. These surveys were not included in the analysis of the survey questions because the participants did not fill out the returned survey. The first question was “How do you calculate adult carboplatin doses at your practice?” A majority of participants (92.6% [n = 54]) responded with the AUC method. Three participants (5.5% [n = 54]) did not answer the first question. Only one participant responded with BSA method (1.9%), and if this answer was chosen, then the survey was to be returned without answering questions 2 Journal of the American Pharmacists Association
through 7. Questions 2 through 6 were multiple-choice answers, and participants could circle all methods that applied and had the option of choosing “other” if the desired method was not stated. When asked who calculates carboplatin AUC doses, multiple health professionals (40% [n = 53]) were selected most commonly. A registered nurse was the most common single response (26% [n = 53]). Respondents who indicated “other” noted an electronic medical record, medical doctor, oncology physician assistant, or computer-calculated carboplatin AUC doses. When asked about double check or verification, the most common selection was multiple clinicians (51%) and the most common single selection was a registered nurse (26%). One respondent indicated that he/she did not double check or verify. When asked about what to do if a patient had a SCr of 0.4 mg/dL, the majority answered that they would use the 0.4 mg/dL in their dose calculation (25%). The second most common response was to use 0.8 mg/dL (15% [n = 53]). Those who answered “other” stated that it was physician dependent, that the CrCl was capped, or that the SCr was rounded to 0.5, 0.7, or 0.9 mg/dL. When asked about the patient weight used in carboplatin calculations, the majority answered actual body weight (57% [n = 53]). Those who answered “other” stated that a different ideal body weight formula was used than that provided in the survey. When asked about which formula was used, the most common response was CG (38% [n = 53]). The second most common response was entering patient data into an automated carboplatin AUC dose calculator on a computer, personal digital assistant, website, slide rule, or standard form. Participant-provided responses for “other” included “slide rule,” “each oncologist uses their own,” or “Chatelut formula.” The Chatelut formula was designed as an alternative to the CF but is not nearly as widely used as the CF or the MCFs and is not discussed in this article. The patient case example provided in online Appendix 1 pertained to the final question of the survey. The case example was reviewed to assess if the carboplatin AUC 6 doses were different at different practices for a single patient with the same patient variables. A total of 47 of 53 (88%) participants answered the case example question. Participants’ responses indicated a carboplatin dose range of 110 to 1,811 mg (mean 978 mg, median 948 mg). We determined a correct dose of 721 mg for the case example question, and only 1 participant (of 47) indicated the same response. In addition, when assessing the case example question, several responses contained errors (15% [n = 53]). Among those responses, 63% (n = 8) involved calculation errors from using the wrong order of operations, such that the formula was accurately written but the calculation method was incorrect. More than one-third (37%) of the errors resulted from omitting certain varij apha.org
Jul /AU G 2013 | 53:4 |
JAPhA 421
Research Notes
ables, such as the female factor in the Jelliffe equation, AUC, or the nonrenal elimination constant 25 in the MCF equation.
Discussion
Carboplatin dosing: Updates and existing issues In October 2010, the Food and Drug Administration (FDA) issued a communication to the oncology community regarding measurement of SCr for use in MCFs.4 FDA stated that the isotope dilution mass spectrometry method used to measure SCr renders values that cause overestimation of GFR determined by formulae when SCr values are less than 0.8 mg/dL.4 Therefore, FDA directed that the carboplatin label state that GFR should not exceed 125 mL/min in patients with normal renal function.4 Although this is a step toward resolving the issues illustrated by the current study, it does not address the variations of formulae used and the different assumptions used to calculate carboplatin doses with those formulae. The abstract of our study was presented before the FDA letter was released; therefore, the option for capping the CrCl was not included in our survey. Evaluation of survey findings Although the use of the actual SCr, actual body weight, and Cockcroft-Gault in MCFs was most common, no consistency was observed in responses for dosing carboplatin. We can only speculate what actually is occurring in practice. In the case example, 27 (57.5%) participants indicated overdosing, 9 (19%) indicated underdosing, and 11 (23.5%) were within 100 mg of our dose (n = 47). The average dose of 978 mg was 257 mg higher than our calculated dose. Authors’ observations We have searched the literature and standardized our carboplatin AUC dose calculation methods. We use the MCF with CG.5–8 We use actual body weight unless the patient’s body mass index (BMI) is greater than 30 kg/ m2. If BMI is greater than 30 kg/m2, we use adjusted body weight.7–10 For SCr values less than 0.8 mg/dL, we round up SCr to 0.8 mg/dL.8,10 Only a large prospective trial can determine if our methods produce carboplatin doses that are sufficiently accurate to compare with the original CF, but at least we are confident that we are using methods that are derived from published peerreviewed research and that all our patients of the same weight, age, SCr, and sex will receive the same dose of carboplatin for a prescribed AUC.
Limitations The survey had a low response rate of 12% (n = 56 of 467). Electronic means of producing the survey were
422 JAPhA | 5 3:4 | JUL /AUG 2013
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researched, but distribution was difficult due to an inability to acquire e-mail addresses for oncology practices and hospital oncology centers. Another limitation involved the reliability and validity of the survey. Also, because this was a survey, respondents may not have been as meticulous as they would for real patients. Finally, because this was a pharmacy practice residency project, full and complete reliability and validity were not determined as a result of time constraints.
Conclusion The survey responses showed variations among participants regarding use of SCr values and body weight values for calculating carboplatin doses. The doses provided by participants were inconsistent, and their interpretation of the variables in the equations varied. More research is needed, and efforts should be made to have a universal MCF with standardized assumptions for body weight and SCr to achieve consistent dosing across practices. References 1. Waddell JA, Solimando DA. Verifying carboplatin doses in adult patients with the Calvert and modified Calvert formulas. Hosp Pharm. 2000;35(9):914–22. 2. Calvert AH, Newell DR, Grumbell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989;7(11):1748–56. 3. Busse T. Carboplatin dosing accounting for the renal and hematologic status of patients. Clin J Oncol Nurs. 2003;7(1):104–5. 4. Food and Drug Administration. Carboplatin dosing. www.fda.gov/ AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm228974.htm. Accessed October 8, 2010. 5. Cathomas R, Harle A, Mead GM, et al. Glomerular filtration rate (GFR) in patients with stage I testicular seminoma treated with adjuvant carboplatin: a comparison of six formulae compared to a radioisotope gold standard [abstract]. J Clin Oncol. 2007;25(18 suppl):15504. 6. de Lemos M, Hsieh T, Hamata L, et al. Evaluation of predictive formulae for glomerular filtration rate for carboplatin dosing in gynecological malignancies. Gynecol Oncol. 2006;103(3):1063–9. 7. Ainsworth NL, Marshall A, Hatcher H, et al. Evaluation of glomerular filtration rate estimation by Cockcroft-Gault, Jelliffe, Wright and Modification of Diet in Renal Disease (MDRD) formulae in oncology patients. Ann Oncol. 2012;23(7):1845–53. 8. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. 9. Hutson PR, Tutsch KD, Pomplun M, et al. Carboplatin dosing in obese patients [abstract]. Proc Am Soc Clin Oncol. 2000;19:187a. 10. Herrington JD, Tran HT, Riggs MW. Prospective evaluation of carboplatin AUC dosing in patients with a BMI ≥27 or cachexia. Cancer Chemother Pharmacol. 2006;57(2):241–7.
Journal of the American Pharmacists Association
Survey of carboplatin dosing strategies in oncology practices Patrick Blankenship and J. Aubrey Waddell
Abstract Objectives: To identify variations in carboplatin dose calculations at oncology institutions and practices in the southeastern United States. Methods: 500 surveys were mailed to oncology practices in the southeastern United States to assess variations in carboplatin doses. The survey sought to determine assumptions that are made regarding carboplatin calculations and if different carboplatin doses result when participants are given the same data and patient characteristics. Results: The survey had a response rate of 12% (n = 56 of 467). The majority of responses used actual serum creatinine and actual body weight. The Cockcroft-Gault creatinine clearance formula was used most commonly. The doses calculated in the case example of an AUC (area under the curve) 6 dose of carboplatin ranged from 110 to 1,811 mg (mean 987 mg, median 963 mg). We determined a correct dose of 721 mg for the case example. Conclusion: The majority of responses to the case example indicated overdosing of carboplatin. Participants provided inconsistent doses, and their interpretation of the variables in the equations varied. More research is needed, and efforts should be made to have a universal modified Calvert formula with standardized assumptions to achieve consistent dosing across practices. Keywords: Area under the curve, carboplatin dosing, carboplatin equations. J Am Pharm Assoc. 2013;53:420–422. doi: 10.1331/JAPhA.2013.12053
C
arboplatin is a broad-spectrum antineoplastic agent used to treat a variety of neoplasms. During the 1980s, carboplatin was primarily dosed using the body surface area (BSA) method. However, since 1989, the area under the curve (AUC) method has predominantly replaced the BSA method as the basis for dosing carboplatin.1,2 The AUC methods most commonly used are the Calvert formula (CF) or one of the modified Calvert formulae (MCFs).1 Nearly three-quarters of an intravenous carboplatin dose is excreted unchanged in the urine. The elimination of carboplatin correlates with glomerular filtration rate (GFR). Calvert et al.2 developed a formula that would decrease doses with poor renal function and increase doses for higher-than-normal renal function. Also, CF helped predict carboplatin-associated toxicities such as thrombocytopenia and leucopenia.1 A radiopharmaceutical method (51Cr-EDTA clearance) was used to accurately determine GFR, as displayed in the original CF equation1: dose = AUC(GFR + 25). However, this method of measuring GFR was not widely used, probably as a result of the expense of radiopharmaceuticals, nonavailability of 51Cr-EDTA in the United States, and inconvenience of the time needed to measure GFR.3 The original CF was modified to substitute the 24-hour creatinine clearance (CrCl) for the radiopharmaceutically determined GFR1: AUC([24-hour CrCl] + 25). This substitution for GFR correlated reasonably well with the original CF, but this determination of renal function also is inconvenient.1 The most convenient and economical method is an estimation of CrCl instead of the approximation measurement. Examples of these MCFs include the Jelliffe formula substituted for GFR, the Cockcroft-Gault formula substituted for GFR, and Received March 7, 2012, and in revised form November 30, 2012. Accepted for publication December 1, 2012. Patrick Blankenship, PharmD, BCPS, is Clinical Pharmacist, Emergency Department, Blount Memorial Hospital, Maryville, TN. J. Aubrey Waddell, PharmD, FAPhA, BCOP, is Professor, College of Pharmacy, University of Tennessee, Knoxville, and Oncology Pharmacist, Blount Memorial Hospital, Maryville, TN. Correspondence: Patrick Blankenship, PharmD, BCPS, Blount Memorial Hospital, 907 East Lamar Alexander Pkwy., Maryville, TN 37804. Fax: 865-981-2258. E-mail: [email protected] Disclosure: The authors declare no conflicts of interest or financial interests in any product or service mentioned in this article, including grants, employment, gifts, stock holdings, or honoraria. Acknowledgments: To Sheila Sands for administrative support. Previous presentation: American Pharmacist Association Annual Meeting & Exposition, March, 12–15, 2010, Washington, DC.
420 JAPhA | 5 3:4 | JUL /AUG 2013
ja p h a .org
Journal of the American Pharmacists Association
Research Notes
the Jelliffe formula (adjusted for BSA) substituted for GFR.1 Various equations are used to estimate GFR; therefore, a potential exists for variation in carboplatin doses.1 In addition, the assumptions and variables in the equations can cause variability in doses. These assumptions include the body weight value that is used (e.g., ideal body weight, adjusted body weight, actual body weight).1 Opinions also may differ regarding serum creatinine (SCr) when the level is lower than normal (e.g., rounding SCr to 0.8 or 1 mg/dL or using actual SCr).1 These concerns have not been evaluated in the literature extensively or addressed in large clinical trials.1
Objective We sought to identify variations in carboplatin dose calculations at oncology institutions and practices in the southeastern United States.
Methods To assess how carboplatin doses were determined, a survey (Appendix 1 in the electronic version of this article, available online at www.japha.org) was distributed by mail to oncology practices and hospitals in the southeastern United States in February to March 2010. The survey contained seven questions, including six multiple-choice questions and one case example question in which participants used given variables to determine or calculate a carboplatin dose. The survey was validated through five local oncology offices for reliability and validity. A public website was used to find the mailing addresses of U.S. oncology practices and centers in the southeastern United States. A total of 500 surveys were mailed with prepaid postage envelopes for returning completed surveys. The participants were given the option to return surveys via facsimile. Institutional review board approval was obtained from the Blount Memorial Hospital and University of Tennessee Health Science Center.
Results Of the 500 mailed surveys, 33 (6.6%) were nondeliverable because of incorrect addresses. A total of 56 (12%) of the remaining 467 surveys were returned. Two of the returned surveys were incomplete due to formulary issues, and one was inadvertently sent to a radiation oncology office. These surveys were not included in the analysis of the survey questions because the participants did not fill out the returned survey. The first question was “How do you calculate adult carboplatin doses at your practice?” A majority of participants (92.6% [n = 54]) responded with the AUC method. Three participants (5.5% [n = 54]) did not answer the first question. Only one participant responded with BSA method (1.9%), and if this answer was chosen, then the survey was to be returned without answering questions 2 Journal of the American Pharmacists Association
through 7. Questions 2 through 6 were multiple-choice answers, and participants could circle all methods that applied and had the option of choosing “other” if the desired method was not stated. When asked who calculates carboplatin AUC doses, multiple health professionals (40% [n = 53]) were selected most commonly. A registered nurse was the most common single response (26% [n = 53]). Respondents who indicated “other” noted an electronic medical record, medical doctor, oncology physician assistant, or computer-calculated carboplatin AUC doses. When asked about double check or verification, the most common selection was multiple clinicians (51%) and the most common single selection was a registered nurse (26%). One respondent indicated that he/she did not double check or verify. When asked about what to do if a patient had a SCr of 0.4 mg/dL, the majority answered that they would use the 0.4 mg/dL in their dose calculation (25%). The second most common response was to use 0.8 mg/dL (15% [n = 53]). Those who answered “other” stated that it was physician dependent, that the CrCl was capped, or that the SCr was rounded to 0.5, 0.7, or 0.9 mg/dL. When asked about the patient weight used in carboplatin calculations, the majority answered actual body weight (57% [n = 53]). Those who answered “other” stated that a different ideal body weight formula was used than that provided in the survey. When asked about which formula was used, the most common response was CG (38% [n = 53]). The second most common response was entering patient data into an automated carboplatin AUC dose calculator on a computer, personal digital assistant, website, slide rule, or standard form. Participant-provided responses for “other” included “slide rule,” “each oncologist uses their own,” or “Chatelut formula.” The Chatelut formula was designed as an alternative to the CF but is not nearly as widely used as the CF or the MCFs and is not discussed in this article. The patient case example provided in online Appendix 1 pertained to the final question of the survey. The case example was reviewed to assess if the carboplatin AUC 6 doses were different at different practices for a single patient with the same patient variables. A total of 47 of 53 (88%) participants answered the case example question. Participants’ responses indicated a carboplatin dose range of 110 to 1,811 mg (mean 978 mg, median 948 mg). We determined a correct dose of 721 mg for the case example question, and only 1 participant (of 47) indicated the same response. In addition, when assessing the case example question, several responses contained errors (15% [n = 53]). Among those responses, 63% (n = 8) involved calculation errors from using the wrong order of operations, such that the formula was accurately written but the calculation method was incorrect. More than one-third (37%) of the errors resulted from omitting certain varij apha.org
Jul /AU G 2013 | 53:4 |
JAPhA 421
Research Notes
ables, such as the female factor in the Jelliffe equation, AUC, or the nonrenal elimination constant 25 in the MCF equation.
Discussion
Carboplatin dosing: Updates and existing issues In October 2010, the Food and Drug Administration (FDA) issued a communication to the oncology community regarding measurement of SCr for use in MCFs.4 FDA stated that the isotope dilution mass spectrometry method used to measure SCr renders values that cause overestimation of GFR determined by formulae when SCr values are less than 0.8 mg/dL.4 Therefore, FDA directed that the carboplatin label state that GFR should not exceed 125 mL/min in patients with normal renal function.4 Although this is a step toward resolving the issues illustrated by the current study, it does not address the variations of formulae used and the different assumptions used to calculate carboplatin doses with those formulae. The abstract of our study was presented before the FDA letter was released; therefore, the option for capping the CrCl was not included in our survey. Evaluation of survey findings Although the use of the actual SCr, actual body weight, and Cockcroft-Gault in MCFs was most common, no consistency was observed in responses for dosing carboplatin. We can only speculate what actually is occurring in practice. In the case example, 27 (57.5%) participants indicated overdosing, 9 (19%) indicated underdosing, and 11 (23.5%) were within 100 mg of our dose (n = 47). The average dose of 978 mg was 257 mg higher than our calculated dose. Authors’ observations We have searched the literature and standardized our carboplatin AUC dose calculation methods. We use the MCF with CG.5–8 We use actual body weight unless the patient’s body mass index (BMI) is greater than 30 kg/ m2. If BMI is greater than 30 kg/m2, we use adjusted body weight.7–10 For SCr values less than 0.8 mg/dL, we round up SCr to 0.8 mg/dL.8,10 Only a large prospective trial can determine if our methods produce carboplatin doses that are sufficiently accurate to compare with the original CF, but at least we are confident that we are using methods that are derived from published peerreviewed research and that all our patients of the same weight, age, SCr, and sex will receive the same dose of carboplatin for a prescribed AUC.
Limitations The survey had a low response rate of 12% (n = 56 of 467). Electronic means of producing the survey were
422 JAPhA | 5 3:4 | JUL /AUG 2013
ja p h a .org
researched, but distribution was difficult due to an inability to acquire e-mail addresses for oncology practices and hospital oncology centers. Another limitation involved the reliability and validity of the survey. Also, because this was a survey, respondents may not have been as meticulous as they would for real patients. Finally, because this was a pharmacy practice residency project, full and complete reliability and validity were not determined as a result of time constraints.
Conclusion The survey responses showed variations among participants regarding use of SCr values and body weight values for calculating carboplatin doses. The doses provided by participants were inconsistent, and their interpretation of the variables in the equations varied. More research is needed, and efforts should be made to have a universal MCF with standardized assumptions for body weight and SCr to achieve consistent dosing across practices. References 1. Waddell JA, Solimando DA. Verifying carboplatin doses in adult patients with the Calvert and modified Calvert formulas. Hosp Pharm. 2000;35(9):914–22. 2. Calvert AH, Newell DR, Grumbell LA, et al. Carboplatin dosage: prospective evaluation of a simple formula based on renal function. J Clin Oncol. 1989;7(11):1748–56. 3. Busse T. Carboplatin dosing accounting for the renal and hematologic status of patients. Clin J Oncol Nurs. 2003;7(1):104–5. 4. Food and Drug Administration. Carboplatin dosing. www.fda.gov/ AboutFDA/CentersOffices/OfficeofMedicalProductsandTobacco/ CDER/ucm228974.htm. Accessed October 8, 2010. 5. Cathomas R, Harle A, Mead GM, et al. Glomerular filtration rate (GFR) in patients with stage I testicular seminoma treated with adjuvant carboplatin: a comparison of six formulae compared to a radioisotope gold standard [abstract]. J Clin Oncol. 2007;25(18 suppl):15504. 6. de Lemos M, Hsieh T, Hamata L, et al. Evaluation of predictive formulae for glomerular filtration rate for carboplatin dosing in gynecological malignancies. Gynecol Oncol. 2006;103(3):1063–9. 7. Ainsworth NL, Marshall A, Hatcher H, et al. Evaluation of glomerular filtration rate estimation by Cockcroft-Gault, Jelliffe, Wright and Modification of Diet in Renal Disease (MDRD) formulae in oncology patients. Ann Oncol. 2012;23(7):1845–53. 8. Cockcroft DW, Gault MH. Prediction of creatinine clearance from serum creatinine. Nephron. 1976;16(1):31–41. 9. Hutson PR, Tutsch KD, Pomplun M, et al. Carboplatin dosing in obese patients [abstract]. Proc Am Soc Clin Oncol. 2000;19:187a. 10. Herrington JD, Tran HT, Riggs MW. Prospective evaluation of carboplatin AUC dosing in patients with a BMI ≥27 or cachexia. Cancer Chemother Pharmacol. 2006;57(2):241–7.
Journal of the American Pharmacists Association