Evaluation of Alternate Size Descriptors for Dose Calculation of Anticancer Drugs in the Obese

2007 ◽  
Vol 25 (30) ◽  
pp. 4707-4713 ◽  
Author(s):  
Alex Sparreboom ◽  
Antonio C. Wolff ◽  
Ron H.J. Mathijssen ◽  
Etienne Chatelut ◽  
Eric K. Rowinsky ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Actual Body ◽  
Lean Body Mass ◽  
Anticancer Drugs ◽  
Body Mass ◽  
Dose Calculation ◽  
Pharmacokinetic Parameters ◽  
Obese Patients ◽  
Actual Body Weight

Purpose Despite the rising prevalence of obesity, there is paucity of information describing how doses of anticancer drugs should be adjusted in clinical practice. Here, we assessed the pharmacokinetics of eight anticancer drugs in adults and evaluated the potential utility of alternative weight descriptors in dose calculation for the obese. Patients and Methods A total of 1,206 adult cancer patients were studied, of whom 162 (13.4%) were obese (body mass index ≥ 30). Pharmacokinetic parameters were calculated using noncompartmental analysis, and compared between lean (body mass index ≤ 25) and obese patients. Results The absolute clearance of cisplatin, paclitaxel, and troxacitabine was significantly increased in the obese (P < .023), but this was not observed for carboplatin, docetaxel, irinotecan, or topotecan (P < .17). For doxorubicin, the systemic clearance was statistically significantly reduced in obese women (P = .013), but not in obese men (P = .52). Evaluation of alternate weight descriptors for dose calculation in the obese, including predicted normal weight, lean body mass, (adjusted) ideal body weight, and the mean of ideal and actual body weight, indicated that, for most of the evaluated drugs, weight scalars used to calculate body-surface area should consider actual body weight regardless of size. Conclusion The results suggest that a number of widely used empiric strategies for dose adjustments in obese patients, including a priori dose reduction or dose capping, should be discouraged.

scholarly journals An Evaluation of Systemic Vancomycin Dosing in Obese Patients

2015 ◽  
Vol 2 (4) ◽  
Author(s):  
David W. Kubiak ◽  
Mohammed Alquwaizani ◽  
David Sansonetti ◽  
Megan E. Barra ◽  
Michael S. Calderwood
Keyword(s):  
Body Mass Index ◽  
Morbid Obesity ◽  
Body Weight ◽  
Actual Body ◽  
Initial Dose ◽  
Ideal Body Weight ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Trough Concentrations ◽  
Ideal Body

Abstract We retrospectively identified 67 patients with severe or morbid obesity (body mass index ≥35 kg/m2) who had received intravenous vancomycin at our institution. We observed that an initial dose of 45 to 65 mg/kg vancomycin per day based upon ideal body weight rather than actual body weight was more predictive of initial trough concentrations between 15 and 20 mcg/mL.

Adjusted versus actual body weight dosing of 4-factor prothrombin complex concentrate in obese patients with warfarin-associated major bleeding

2018 ◽  
Vol 47 (3) ◽  
pp. 369-374 ◽  
Author(s):  
Keaton S. Smetana ◽  
Rachel Ziemba ◽  
Casey C. May ◽  
Michael J. Erdman ◽  
Edward T. Van Matre ◽  
...  
Keyword(s):  
Body Weight ◽  
Actual Body ◽  
Major Bleeding ◽  
Prothrombin Complex Concentrate ◽  
Obese Patients ◽  
Actual Body Weight

P0708ASSOCIATION OF OBESITY WITH KIDNEY CYST GROWTH IN PATIENTS WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE; RESULTS FROM KNOW-CKD COHORT DATA

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Chang Seong Kim ◽  
Hong Sang Choi ◽  
Eun hui Bae ◽  
Seong Kwon Ma ◽  
Soo Wan Kim
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Body Mass ◽  
Autosomal Dominant ◽  
Obese Patients ◽  
Polycystic Kidney ◽  
Autosomal Dominant Polycystic Kidney

Abstract Background and Aims Overweight or obese patients with autosomal dominant polycystic kidney disease (ADPKD) are associated with the decline of glomerular filtration rate. However, little is known about the annual rate of change in total kidney volume (TKV) in patients with ADPKD according to the body mass index (BMI) corrected by TKV and total liver volume (TLV). Method We analyzed 364 patients with ADPKD from the KoreaN Cohort Study for Outcomes in Patients with Chronic Kidney Disease. We compared the changes in TKV in less than 1-year, 2-years and 4-year follow-up from patients by dividing baseline body mass index (BMI) by 18.5 to 22.9 (normal), 23 to 24.9 (overweight), and &gt; 25 kg/m2 (obesity). Results During the 4-year follow-up period, TKV tended to increase statistically with increasing BMI (P = 0.032). Similarly, higher BMI group showed higher TKV than lower BMI group (P = 0.016). Conventional BMI is affected by TKV and TLV in advanced ADPKD patients. Therefore, we reclassified patients by corrected BMI using the adjusted body weight (body weight – TKV – TLV). Although the statistical significances between absolute value of TKV and corrected BMI groups were disappeared during the follow-up, TKV% change/year showed significantly higher in ADPKD patients with obesity among corrected BMI groups (normal; 20.2%, overweight; 17.6% and obesity; 30.6%, P for trend = 0.022) Conclusion Even after correcting the TKV and TVL, obese patients showed a high of TKV% change/year compared to non-obese patients with ADPKD.

A universal formula based on cystatin C to perform individual dosing of carboplatin in normal weight, underweight, and obese patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 2527-2527
Author(s):  
E. Chatelut ◽  
A. Schmitt ◽  
A. Lansiaux ◽  
C. Bobin-Dubigeon ◽  
M. Etienne-Grimaldi ◽  
...  
Keyword(s):  
Body Weight ◽  
Lean Body Mass ◽  
Body Mass ◽  
Cystatin C ◽  
Ideal Body Weight ◽  
Normal Weight ◽  
Percentage Error ◽  
Pharmacokinetic Analysis ◽  
Obese Patients ◽  
Ideal Body

2527 Background: It has recently been shown that it is possible to improve the prediction of carboplatin clearance by adding plasma cystatin C level (cysC), an endogenous marker of glomerular filtration rate, to the other patient characteristics routinely used for carboplatin individual dosing, namely serum creatinine (Scr), body weight (BW), age, and sex. This multi-center pharmacokinetic study was performed to evaluate prospectively the benefit of using cysC for carboplatin individual dosing. Methods: The 357 patients included in the study were receiving carboplatin as part of established protocols. A population pharmacokinetic analysis was performed using the NONMEM program. Seven covariates were studied: Scr, cysC, age, sex, BW, ideal body weight, and lean body mass. Results: The best covariate equation was: carboplatin clearance (mL/min) = 105. (Scr/75)-0.433. (cysC/1.00)-0.290 . (BW/65)+0.547 . (age/56)-0.351 . 0.855sex, with Scr in μmol/L, cysC in mg/L, BW in kg, age in years, and sex = 0 for male. Using an alternative weight descriptor (ideal body weight or lean body mass) did not improve the prediction. This final covariate model was validated by bootstrap analysis. The bias (mean percentage error) and imprecision (mean absolute percentage error) were +2% and 15% respectively on the total population, and were of a similar magnitude in each of the three subgroups of patients defined according to their body mass index. Conclusions: For the first time, a unique formula is proposed for carboplatin individual dosing to patients which is shown to be equally valid for underweight, normal weight, and obese patients. No significant financial relationships to disclose.

scholarly journals The effects of three-week fasting diet on blood pressure, lipid profile and glucoregulation in extremely obese patients

2007 ◽  
Vol 135 (7-8) ◽  
pp. 440-446 ◽  
Author(s):  
Biljana Beleslin ◽  
Jasmina Ciric ◽  
Milos Zarkovic ◽  
Zorana Penezic ◽  
Svetlana Vujovic ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Body Mass Index ◽  
Body Weight ◽  
Insulin Sensitivity ◽  
Lipid Profile ◽  
Body Mass ◽  
Glucose Intolerance ◽  
The Body ◽  
Obese Patients

Introduction Obesity is often accompanied by a number of complications including diabetes mellitus and cardiovascular diseases. Elevated blood pressure and lipids, as well as deterioration of glucoregulation are attributed, as the most significant factors, to development of diabetes mellitus and cardiovascular complications in obese patients. Objective The aim of our study was to evaluate the effects of a fasting diet on blood pressure, lipid profile and glucoregulatory parameters. Method We included 110 patients (33 male and 77 female; mean age 35?1 years, body weight 131.7?2.6 kg, body mass index 45.4?0.8 kg/m2) who were hospitalized for three weeks for the treatment of extreme obesity with the fasting diet. At the beginning, during, and at the end of this period, we evaluated changes in blood pressure, lipid profile, as well as parameters of glucoregulation including glycaemia, insulinaemia, and insulin sensitivity by HOMA. Oral glucose tolerance test (OGTT) was performed in all patients at the beginning and at the end of the fasting diet. Results During the fasting diet, the body weight decreased from 131.7?2.6 kg to 117.7?2.4 kg (p<0.001), the body mass index decreased from 45.4?0.8 kg/m2 to 40.8?0.8 kg/m2 (p<0.001), and both systolic and diastolic blood pressure significantly declined (143?2 vs. 132?2 mm Hg, p<0.001; 92?2 vs. 85?2 mm Hg, p<0.001). In addition, the fasting diet produced a significant decrease in total cholesterol, LDL cholesterol, triglycerides, as well as basal glycaemia and insulinaemia (p<0.001) Before the fasting diet, OGTT was normal in 76% of patients, whereas 21% of patients showed glucose intolerance, and 4% of patients diabetes mellitus. After the fasting diet, OGTT was normal in 88% of patients, whereas 12% of patients still had signs of glucose intolerance (p<0.05). In addition, insulin resistance significantly (p<0.05) increased from 54?6% to 89?13% after the fasting diet. Conclusion The three-week fasting diet in extremely obese patients produced a significant decrease and normalization of blood pressure, decrease in lipids, and improvement in glucoregulation including the increase in insulin sensitivity.

scholarly journals TRAUMATIC DISEASE PECULIARITIES COURSE, ITS DIAGNOSTICS AND TREATMENT AT POLYTRAUMA IN SUFFER OBESE PATIENTS

2019 ◽  
Vol 43 (4) ◽  
pp. 47-53
Author(s):  
S.D. Khimich ◽  
O. M. Chemerys
Keyword(s):  
Body Mass Index ◽  
Body Weight ◽  
Body Mass ◽  
Overweight And Obesity ◽  
The Body ◽  
Obese Patients ◽  
Prognostic Features ◽  
Normal Body ◽  
Significant Difference ◽  
Normal Body Weight

Abstract Introduction. It’s known that the issue of polytrauma is one of the most urgent problems of surgery, and among injured patients a special approach is required for patients with overweight and obesity of varying degrees. Purpose of the study. To study prognostic features of traumatic disease course and to improve the results of diagnostics and surgical treatment of patients with polytrauma suffer obesity. Materials and methods. Clinical material was made up of 106 patients with combined body trauma, which were divided into three groups according to body mass index. Results. The results of the research showed a significant difference in the course of traumatic disease in patients with normal body weight and obesity. In particular, in the process of diagnostics of blunt chest and abdominal trauma the frequency of application of interventional methods of diagnostics was directly proportional to the increase of body mass index. The course of traumatic disease in the obese patients had a number of characteristic features that formed the basis for the development of diagnostics and differential program of treatment. Conclusions. The results of the research showed that the course of traumatic disease in combined injury obese patients is directly proportional to the body mass index and has certain features that differentiate them from patients with normal body weight. Keywords: polytrauma, obesity, traumatic disease, diagnostics, treatment.

Chemotherapy Dose Adjustment For Obese Patients Undergoing Hematopoietic Stem Cell Transplantation (HSCT): A Survey On Behalf Of The ALWP Of The EBMT

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4535-4535
Author(s):  
Noga Shem-Tov ◽  
Myriam Labopin ◽  
Leila Moukhtari ◽  
Fabio Ciceri ◽  
Jordi Esteve ◽  
...  
Keyword(s):  
Body Weight ◽  
Actual Body ◽  
Dose Adjustment ◽  
Ideal Body Weight ◽  
High Dose ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Hematopoietic Stem ◽  
Chemotherapy Dose ◽  
Ideal Body

Rates of obesity have substantially increased in recent years. Pharmacokinetics of drugs including chemotherapy is different in obese patients due to alteration in the clearance and volume of distribution. Thus, appropriate chemotherapy dosing for obese patients with malignant diseases is a significant issue. Limiting chemotherapy doses in overweight and obese patients may negatively influence the outcomes in these patients. ASCO has recently published clinical practice guidelines for conventional chemotherapy dosing for obese patients with cancer indicating that up to 40% of obese patients received reduced chemotherapy doses that are not based on actual body weight (ABW) [Grigg A, JCO 2012]. Concerns about toxicity or overdosing in obese patients, based on the use of ABW, are unfounded. Moreover, there is a paucity of information addressing the pharmacokinetics of high dose chemotherapy in obese patients undergoing hematopoietic stem cell transplantation (HSCT). A rather small international survey of drug dosing schemes among transplant centers revealed that there is no consensus regarding appropriate dose adjustment for obese patients [Grigg A, Leuk Lymphoma 1997]. Also, there is limited data on outcomes in obese versus non-obese patients in various small retrospective studies. For this reason, the ALWP of the EBMT constructed an electronic survey for assessing current practice of dose adjustment of chemotherapy in patients undergoing HSCT, in transplant centers and for planning retrospective analysis and prospective studies in the future. Fifty six EBMT centers from 27 countries filled the online survey. Among the 56 centers, the percentage of obese patients was less than 10% in 22 centers (40%), between 10 to 19% in 23 centers (42%) and more than 20% in 10 centers (17%). Forty five centers declared they adjust chemotherapy dose for obese patients (80.5%) and only 11 (19.5%) declared they do not adjust dose. Among centers which adjust dose, most uses BMI as the parameter for defining obesity (28 centers, 62%), others use percentage over the actual body weight (ABW) as the basis for defining obesity (11 centers, 24.5%), both BMI and ABW (3 centers, 6.7%) or other parameter (3 centers, 6.7%). Most of the centers that use BMI for adjusting dose define BMI > 30 kg/m2 as the cut-off value (formal definition for obesity), only one center uses morbid obesity (BMI > 40 kg/m2), and the remainder uses other cut-off values. Among 11 centers who use ABW, 9 use ABW more than 120% of ideal body weight for adjustment. Eighty four percents of the centers use one level of obesity for adjustment while the rest uses 2 levels. The method for determining the weight for chemotherapy calculation was actual body weight (ABW) in 16 centers, ideal body weight (IBW) in 10 centers, IBW + 25% of difference between IBW and ABW (IBW+0.25*(ABW-IBW)) in 16 centers and other methods in the rest. Among centers that use dose adjustment, 44% also cap the dose at 2 m2 for chemotherapy dose based on BSA while 56% do not cap. On the contrary, most of the centers (9/11) that do not adjust dose for weight also do not cap the BSA at 2 m2. Seventy nine percents of responding centers use the same approach to dose adjustments for myeloablative, reduced intensity (RIC) or non myeloablative (NMA) conditioning, while 21% reduce the dose less for RIC or NMA conditioning. For Busulfan dose only 7 centers monitor pharmacokinetics (pk). Eleven centers use ideal body weight for calculation, 17 centers use actual weight and 18 centers correct weight according to percentage over actual body weight. Conclusion This EBMT survey reveal large diversity among transplant centers regarding dose adjustment practice for high dose conditioning chemotherapy. Most of the EBMT centers use dose adjustment for obese patients and about half of them also cap BSA at 2 m2, while capping is uncommon in the centers that do not adjust dose. Thus, the range of the final dose is very wide. Even for Busulfan where dose is calculated normally according to ideal body weight, the diversity of dose given for obese patients is wide. Our next step is to analyze outcomes of transplantation according to dose adjustment practice and subsequently to formulate a methodology for future prospective studies. Disclosures: No relevant conflicts of interest to declare.

Relationship between toxicity and obesity in women receiving adjuvant chemotherapy for breast cancer: results from cancer and leukemia group B study 8541.

1996 ◽  
Vol 14 (11) ◽  
pp. 3000-3008 ◽  
Author(s):  
G L Rosner ◽  
J B Hargis ◽  
D R Hollis ◽  
D R Budman ◽  
R B Weiss ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Weight ◽  
Confidence Interval ◽  
Actual Body ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Obese Women ◽  
Actual Weight ◽  
Group B ◽  
Leukemia Group

PURPOSE We examined data from a large clinical trial to determine if chemotherapy dosing according to actual body weight places obese patients at greater risk of toxicity. PATIENTS AND METHODS Cancer and Leukemia Group B (CALGB) study 8541, a randomized study of schedule and dose of adjuvant cyclophosphamide, doxorubicin, and fluorouracil (CAF) for stage II breast cancer patients with positive regional lymph nodes, provided data on 1,435 women for analysis. Using body-mass index (BMI), we classified a woman as obese if her BMI was > or = 27.3 kg/m2; doses were considered weight-based if within 5% of values calculated using actual weight. Our primary analysis concerned toxicity risks during cycle 1. RESULTS Among women who received weight-based doses of the most dose-intensive CAF regimen, 47% of obese and 51% of nonobese women experienced severe hematologic toxicity (grade > or = 3) during cycle 1 (P = .51, two-tailed). The overall risk ratio (obese v nonobese) of treatment failure among women who received weight-based doses during cycle 1 was 1.02 (95% confidence interval, 0.83 to 1.26), stratified by treatment and adjusted for number of positive nodes, menopausal status, hormone receptor status, and tumor size. The overall adjusted failure risk ratio (weight-based v reduced initial doses) was 0.73 (95% confidence interval, 0.53 to 1.00) among obese women. CONCLUSION Obese patients initially dosed (within 5%) by actual weight did not experience excess cycle 1 toxicity or worse outcome compared with nonobese women dosed similarly. The data suggest that obese women who received reduced doses in cycle 1 experienced worse failure-free survival. We recommend that initial doses of CAF be computed according to actual body weight.

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