scholarly journals Effects of Obesity on the Efficacy and Toxicity of Induction Chemotherapy in Adult Acute Lymphoblastic Leukemia (ALL)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1290-1290
Author(s):  
Tim J Peterson ◽  
Andrew Lin ◽  
Patrick Hilden ◽  
Sean Devlin ◽  
Nelly G. Adel ◽  
...  
Keyword(s):  
Body Weight ◽  
Actual Body ◽  
Induction Chemotherapy ◽  
Lymphoblastic Leukemia ◽  
Performance Status ◽  
Retrospective Chart Review ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Obese Adults ◽  
Grade 3

Abstract Background The efficacy and toxicity of induction regimens for acute lymphoblastic leukemia (ALL) are affected by numerous patient and regimen specific variables including age, performance status, cytogenetics, comorbidities, and the selection and dosing of chemotherapeutic agents. Notably, the incidence of leukemia and the ability to achieve remission have been shown to be affected by obesity.1,2 Although there is a lack of data in obese adults with ALL, previous studies have confirmed the poor prognostic implications of obesity in pediatric patients.3 Current practice with regard to chemotherapy dosing in obese patients is dependent on the American Society of Clinical Oncology (ASCO) guidelines, which recommend that chemotherapy should be dosed on actual body weight, regardless of obesity status.4 With the lack of data in obese adults with ALL, it has been postulated that empirically reducing chemotherapy doses may worsen their prognosis. This provided the rationale for this investigation into the effect of obesity on the efficacy and toxicity of induction chemotherapy in adults with ALL. Methods The primary objective of this study was to evaluate complete remission (CR) rate to initial induction chemotherapy of obese patients (defined as actual body weight (ABW) > 130% of ideal body weight (IBW)), compared to that of non-obese patients. Secondary objectives included overall survival (OS), relapse free survival (RFS), time to platelet and absolute neutrophil count (ANC) recovery, and grade 3/4 non-hematologic toxicities as graded by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). OS and RFS were estimated by the Kaplan-Meier method, with differences across groups accessed via the logrank test. The incidence of CR was estimated by the cumulative incidence method for competing risks, with differences across groups accessed via Gray's test. Death was considered a competing risk for CR. This retrospective chart review included patients with ALL who received initial induction chemotherapy between January 1, 2003, and December 31, 2013, at Memorial Sloan Kettering Cancer Center (MSKCC). Patients included were > 18 years old, newly diagnosed with ALL who were chemotherapy-naïve for treatment of ALL. Results Seventy-two patients were identified during the specified period with a median age at diagnosis for all patients of 46 years (18-86). Patients were primarily excluded as chemotherapy was initiated prior to establishing care with MSKCC. A majority of patients received multi-agent chemotherapy with ALL2, L-20, NY-II, ECOG2993, and CALGB 10403 with a smaller subset of patients of older age or poor performance status treated with vincristine and steroids. Twenty-three patients were identified as being obese with a median of 154% of their IBW. The median % of IBW among the non-obese patients (49 patients) was 115%. All patients received chemotherapy based on body surface area (BSA) calculated on total body weight. All patients in the obese group and 96% of non-obese patients experienced at least one grade 3 or 4 non-hematologic toxicity. Time to ANC recovery (26 days vs. 31 days, for obese and non-obese patients respectively) and platelet recovery (29 days vs. 35 days, respectively) were not different between groups. There was no difference in the cumulative incidence of CR among obese and non-obese patients (p=0.477), with a 1 year incidence of 96% in both groups. RFS was similar among obese and non-obese patients (p=0.203, 36.4% and 52.9% respectively at 3 years). Similarly, there was no significant difference in OS between obese and non-obese patients (p=0.161, 45.5% and 57.1% respectively at 3 years). Univariate analyses demonstrated that there was no significant effect of intensity of regimen utilized or baseline cytogenetics on relapse free survival or overall survival. Conclusion The findings of this retrospective chart review are consistent with current ASCO guidelines for dosing in obese patients. As there were no differences noted in efficacy or safety between obese and non-obese patients in our study, it remains appropriate to continue dosing obese patients based on actual body weight. Further prospective evaluations are necessary to confirm these findings. References Pulte et al. PloS ONE 2014; 9: e85554. Castillo JJ et al. Leuk Res 2012; 36:868-875. Butturini AM et al. Journ Clin Onc 2007; 25(15):2063-2069. Griggs JJ et al. J Clin Oncol 2012; 30(13): 1553-61. Disclosures No relevant conflicts of interest to declare.

Toxicity of chemotherapy dosing using actual body weight in obese versus normal-weight patients: A systematic review and meta-analysis.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6013-6013
Author(s):  
Kathryn Cunningham Hourdequin ◽  
William Lewis Schpero ◽  
Breanne Lee Piazik ◽  
Dorothy R McKenna ◽  
Robin Joyce Larson
Keyword(s):  
Systematic Review ◽  
Body Weight ◽  
Actual Body ◽  
Meta Analysis ◽  
Normal Weight ◽  
Cochrane Library ◽  
Hematologic Toxicity ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Grade 3

6013 Background: Because weight-based chemotherapy calculations can be very large in obese patients, oncologists often empirically reduce doses due to fear of excess toxicity. The resulting underdosing may negatively impact survival. We performed a systematic review and meta-analysis to determine whether, among adults receiving chemotherapy dosed by actual body weight (ABW), obese patients experience differing toxicity or survival compared to normal-weight patients. Methods: We searched MEDLINE, Cochrane Library, Web of Science, and ClinicalTrials.gov through October 2011 and reviewed reference lists. We included studies that compared outcomes of obese versus normal-weight adults receiving chemotherapy dosed according to ABW (+/- 5% variability). Studies followed subjects for at least one cycle of chemotherapy and reported at least one pre-specified outcome. Two authors independently abstracted data from eligible studies. We used random effects models to pool odds ratios (OR) for hematologic and non-hematologic toxicities. We summarized survival qualitatively. Results: Of 3,921 studies, five met inclusion criteria, for a total of 6,877 subjects. Based on three studies, Grade 3/4 hematologic toxicity occurred less often in obese patients than normal-weight patients (OR 0.68, 95% CI 0.51-0.89, I2=29%). A fourth study comparing leukocyte nadirs had variable results depending on the regimen, dosing, and patient co-morbidities. Based on two studies, Grade 3/4 non-hematologic toxicity occurred less often in obese patients than normal-weight patients (OR 0.74, 95% CI 0.63-0.87, I2=0%). A third study found rates of infection did not significantly differ. Three of four studies reported reduced overall survival in obese patients (statistical significance not reported). Conclusions: Contrary to common belief, obese patients receiving chemotherapy based on ABW appear to have lower rates of both hematologic and non-hematologic toxicities compared to normal-weight patients. These results do not support the practice of empiric dose reduction in obese patients. Further research should explore etiologies for the reduced survival in this group.

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

Impact of Increased Body Weight on Acute Toxicity and Outcome of Autologous Stem Cell Transplantation for Non-Hodgkin’s Lymphoma: A Southwest Oncology Group Analysis.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 352-352 ◽  
Author(s):  
Patrick Stiff ◽  
Joseph Unger ◽  
Stephen Forman ◽  
Michael LeBlanc ◽  
Thomas Miller ◽  
...  
Keyword(s):  
Body Weight ◽  
Stem Cell ◽  
Actual Body ◽  
Death Rate ◽  
Skin Toxicity ◽  
High Dose ◽  
Cell Transplant ◽  
Actual Body Weight ◽  
Grade 5 ◽  
Grade 3

Abstract Little is known about the optimal dosing of chemotherapy agents in patients significantly above their ideal body weight (IBW) who undergo high dose therapy with an autologous or allogeneic hematopoietic stem cell transplant. While dose attenuation is often advocated for overweight patients and appears to reduce acute toxicities, its effect on progression-free and overall survival (PFS/OS) is unknown. Due to a high relapse rate after autografts for relapsed/refractory NHL, SWOG has long investigated the use of augmented preparative regimens that utilize high-dose etoposide based on actual body weight (ABW) of 60 mg/kg, along with 12 Gy of TBI and cyclophosphamide (100 mg/kg) which is dosed on unadjusted IBW. We determined acute toxicities and PFS/OS using this approach in a recently completed study (S9438) of 358 patients undergoing autografts for relapsed/refractory NHL, comparing all grade 5 toxicities, grade 3–4 skin toxicities (known to be associated with high dose etoposide) and all other grade 4 toxicities in patients in this study based on % above IBW. The Devine formula for IBW with an adjustment for patients <5 feet was used. Patients at or below their IBW were dosed using their actual body weight. All patients received the preparative regimen as stated followed by autologous peripheral blood stem cells. Overall there were 31 patients with grade 5 toxicities. This group was a mean 42% above their IBW vs 24% for those surviving transplant (p=.001). Increasing % above IBW predicted grade 5 toxicity (p=.002). Even those at or 10% above their IBW had a higher toxic death rate (10.1 vs 3.6%; p=.04). While increasing weight above IBW did not predict for grade 4 lung, liver, cardiac toxicities or infections (p=.12), it did predict for grade 3/4 skin toxicities (p< .001). Skin toxicity, most commonly hand/foot syndrome was seen at rates up to 27.3% vs 7.3% for those ≥ 50 vs < 50% over IBW (p < .001). However, even those just ≥ 10% over IBW had nearly a 4 fold higher risk of skin toxicity (13.4 vs 3.6%; p=.005). While survival by % over IBW is confounded by comorbidities in overweight patients, we found no evidence of a different 2-year PFS or OS for overweight patients, even those ≥ 50% above IBW (PFS=42 vs 45%, p = .28; OS=52 vs 62%, p = .38). These multicenter trial data do establish a correlation of the ABW dosing of etoposide with significant skin toxicity. Without an apparent later PFS/OS benefit to the use of unadjusted etoposide dosing for overweight patients but higher acute skin toxicity and a higher early death rate, etoposide will be dosed using adjusted IBW [ IBW + .4 (ABW − IBW)] in subsequent studies of this regimen.

Impact of weight and creatinine measurements in carboplatin dosing.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13027-e13027 ◽  
Author(s):  
Feriel Boumedien ◽  
Youri Arsenault ◽  
Nathalie LeTarte
Keyword(s):  
Body Weight ◽  
Serum Creatinine ◽  
Actual Body ◽  
Retrospective Chart Review ◽  
Actual Body Weight ◽  
Calculated Dose ◽  
The Difference ◽  
The Impact ◽  
Carboplatin Dose ◽  
Creatinine Measurement

e13027 Background: Controversy surrounding weight in Carboplatin dosing is still current. Also, new methods of measuring serum creatinine have raised more questions regarding the precision of Carboplatin dose calculations. The two objectives of this study were to evaluate the impact of alternative weight indicators (actual and adjusted body weight) in the Cockcroft–Gault equation and the use of different creatinine measurements (standard and IDMS) in order to accurately predict Carboplatin dose. Methods: We performed a retrospective chart review on all patients who received at least one dose of Carboplatin between March 7th and May 8th 2010. The patients were divided into two groups according to their body mass index (BMI): 20 < BMI < 27 and BMI ≥ 27. The differential creatinine clearance and Carboplatin dose were assessed in each group using the actual body weight and the adjusted body weight with IDMS creatinine. Moreover, for patients who had their creatinine measurement at the CHUM hospital, we calculate the difference in Carboplatin dose by using the standard creatinine (SC) measurement and IDMS creatinine with the same weight. Results: A total of 95 patients, representing 119 Carboplatin doses, were included in the analysis. 82% were women and median age was 63. The average BMI was 26,6. The Carboplatin expected AUC was 5 for 89% of patients and Carboplatin was associated to Paclitaxel in 78% of patients. In patients with a 20<BMI< 27 (44%), the average difference between the calculated dose using their actual body weight and adjusted body weight was +6.03% (95% CI, 5.2 to 6.9%). For patients with a BMI ≥ 27 (43%), the mean dose difference was +20.6% (95% CI, 18.8 to 22.5%). The use of SC or IDMS creatinine led to a discrepancy in doses of 5.2% (95% CI, 4.7 to 5.7%) for patients with BMI <27 (35 patients) and 5.5% (95% CI, 4.9 to 6.2%) for those with BMI ≥ 27 (23 patients). Conclusions: Based on these findings, we decide in our clinic, to use the actual body weight for patients with a BMI between 20 and 27, and the adjusted body weight for those with a BMI ≥ 27. We also chose not to modify our doses based on the type of the serum creatinine measurement.

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.

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.

scholarly journals Daptomycin dosing in obese patients: analysis of the use of adjusted body weight versus actual body weight

2019 ◽  
Vol 6 ◽  
pp. 204993611882023 ◽  
Author(s):  
Ashley N. Fox ◽  
Winter J. Smith ◽  
Katherine E. Kupiec ◽  
Stephanie J. Harding ◽  
Beth H. Resman-Targoff ◽  
...  
Keyword(s):  
Body Weight ◽  
Actual Body ◽  
Creatine Phosphokinase ◽  
Obese Patients ◽  
Actual Body Weight ◽  
Clinical Failure ◽  
Limited Information ◽  
Single Center ◽  
Historical Cohort ◽  
Patient Reported

Background: Food and Drug Administration–approved daptomycin dosing uses actual body weight, despite limited dosing information for obese patients. Studies report alterations in daptomycin pharmacokinetics and creatine phosphokinase elevations associated with higher weight-based doses required for obese patients. Limited information regarding clinical outcomes with alternative daptomycin dosing strategies in obesity exists. Objective: This study evaluates equivalency of clinical and safety outcomes in obese patients with daptomycin dosed on adjusted body weight versus a historical cohort using actual body weight. Methods: This retrospective, single center study compared equivalency of outcomes with two one-sided tests in patients with body mass index ⩾30 kg/m2 who received daptomycin dosed on actual body weight versus adjusted body weight. The primary outcome was clinical failure. Secondary outcomes included 90-day readmission and 90-day mortality. A combined safety endpoint included creatine phosphokinase elevation, patient-reported myopathy, and rhabdomyolysis. Results: A total of 667 patients were screened for inclusion; 101 patients were analyzed with 50 in the actual body weight cohort and 51 in the adjusted body weight cohort. The two regimens were statistically equivalent for clinical failure (2% actual body weight versus 4% adjusted body weight; p < 0.001 for equivalency). The two regimens were also statistically equivalent for 90-day mortality (6% actual body weight versus 4% adjusted body weight; p = 0.0014 for equivalency). Limitations include single center, retrospective design, and sample size. Daptomycin dosing intensified throughout the study period. Conclusion: The two daptomycin dosing cohorts were statistically equivalent for both clinical failure and 90-day mortality. More data are needed to assess outcomes with higher (⩾8 mg/kg/day) daptomycin doses in this patient population.

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