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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Review Article

Chemotherapy and Anticancer Drugs Adjustment in Obesity: A Narrative Review

Author(s): João Pedro Thimotheo Batista*, Lucas Alexandre Santos Marzano, Renata Aguiar Menezes Silva, Karla Emília de Sá Rodrigues and Ana Cristina Simões e Silva

Volume 30, Issue 9, 2023

Published on: 23 September, 2022

Page: [1003 - 1028] Pages: 26

DOI: 10.2174/0929867329666220806140204

Price: $65


Background: Obese individuals have higher rates of cancer incidence and cancer- related mortality. The worse chemotherapy outcomes observed in this subset of patients are multifactorial, including the altered physiology in obesity and its impact on pharmacokinetics, the possible increased risk of underdosing, and treatment-related toxicity.

Aims: The present review aimed to discuss recent data on physiology, providing just an overall perspective and pharmacokinetic alterations in obesity concerning chemotherapy. We also reviewed the controversies of dosing adjustment strategies in adult and pediatric patients, mainly addressing the use of actual total body weight and ideal body weight.

Methods: This narrative review tried to provide the best evidence to support antineoplastic drug dosing strategies in children, adolescents, and adults.

Results: Cardiovascular, hepatic, and renal alterations of obesity can affect the distribution, metabolism, and clearance of drugs. Anticancer drugs have a narrow therapeutic range, and variations in dosing may result in either toxicity or underdosing. Obese patients are underrepresented in clinical trials that focus on determining recommendations for chemotherapy dosing and administration in clinical practice. After considering associated comorbidities, the guidelines recommend that chemotherapy should be dosed according to body surface area (BSA) calculated with actual total body weight, not an estimate or ideal weight, especially when the intention of therapy is the cure.

Conclusion: The actual total body weight dosing appears to be a better approach to dosing anticancer drugs in both adults and children when aiming for curative results, showing no difference in toxicity and no limitation in treatment outcomes compared to adjusted doses.

Keywords: Obesity, pharmacokinetics, cancer chemotherapy, antineoplastics, dose adjustment, body-surface area, pediatrics, actual total body weight, ideal body weight.

WHO. Obesity and overweight. 2022. Available from: (Accessed: June 9, 2022).
Reeves, G.K.; Pirie, K.; Beral, V.; Green, J.; Spencer, E.; Bull, D. Cancer incidence and mortality in relation to body mass index in the Million Women Study: Cohort study. BMJ, 2007, 335(7630), 1134.
[] [PMID: 17986716]
Brill, M.J.; Diepstraten, J.; van Rongen, A.; van Kralingen, S.; van den Anker, J.N.; Knibbe, C.A. Impact of obesity on drug metabolism and elimination in adults and children. Clin. Pharmacokinet., 2012, 51(5), 277-304.
[] [PMID: 22448619]
Smit, C.; De Hoogd, S.; Brüggemann, R.J.M.; Knibbe, C.A.J. Obesity and drug pharmacology: A review of the influence of obesity on pharmacokinetic and pharmacodynamic parameters. Expert Opin. Drug Metab. Toxicol., 2018, 14(3), 275-285.
[] [PMID: 29431542]
Sparreboom, A.; Wolff, A.C.; Mathijssen, R.H.; Chatelut, E.; Rowinsky, E.K.; Verweij, J.; Baker, S.D. Evaluation of alternate size descriptors for dose calculation of anticancer drugs in the obese. J. Clin. Oncol., 2007, 25(30), 4707-4713.
[] [PMID: 17947717]
Harskamp-van Ginkel, M.W.; Hill, K.D.; Becker, K.C.; Testoni, D.; Cohen-Wolkowiez, M.; Gonzalez, D.; Barrett, J.S.; Benjamin, D.K., Jr; Siegel, D.A.; Banks, P.; Watt, K.M. Drug dosing and pharmacokinetics in children with obesity: A systematic review. JAMA Pediatr., 2015, 169(7), 678-685.
[] [PMID: 25961828]
Morgan, D.J.; Bray, K.M. Lean body mass as a predictor of drug dosage. Implications for drug therapy. Clin. Pharmacokinet., 1994, 26(4), 292-307.
[] [PMID: 8013162]
Griggs, J.J.; Bohlke, K.; Balaban, E.P.; Dignam, J.J.; Hall, E.T.; Harvey, R.D.; Hecht, D.P.; Klute, K.A.; Morrison, V.A.; Pini, T.M.; Rosner, G.L.; Runowicz, C.D.; Shayne, M.; Sparreboom, A.; Turner, S.; Zarwan, C.; Lyman, G.H. Appropriate systemic therapy dosing for obese adult patients with cancer: ASCO guideline update. J. Clin. Oncol., 2021, 39(18), 2037-2048.
[] [PMID: 33939491]
Butturini, A.M.; Dorey, F.J.; Lange, B.J.; Henry, D.W.; Gaynon, P.S.; Fu, C.; Franklin, J.; Siegel, S.E.; Seibel, N.L.; Rogers, P.C.; Sather, H.; Trigg, M.; Bleyer, W.A.; Carroll, W.L. Obesity and outcome in pediatric acute lymphoblastic leukemia. J. Clin. Oncol., 2007, 25(15), 2063-2069.
[] [PMID: 17513811]
Gelelete, C.B.; Pereira, S.H.; Azevedo, A.M.; Thiago, L.S.; Mundim, M.; Land, M.G.; Costa, E.S. Overweight as a prognostic factor in children with acute lymphoblastic leukemia. Obesity (Silver Spring), 2011, 19(9), 1908-1911.
[] [PMID: 21720424]
Orgel, E.; Sposto, R.; Malvar, J.; Seibel, N.L.; Ladas, E.; Gaynon, P.S.; Freyer, D.R. Impact on survival and toxicity by duration of weight extremes during treatment for pediatric acute lymphoblastic leukemia: A report from the Children’s Oncology Group. J. Clin. Oncol., 2014, 32(13), 1331-1337.
[] [PMID: 24687836]
Conway, B.; Rene, A. Obesity as a disease: No lightweight matter. Obes. Rev., 2004, 5(3), 145-151.
[] [PMID: 15245383]
Redinger, R.N. The pathophysiology of obesity and its clinical manifestations. Gastroenterol. Hepatol. (N.Y.), 2007, 3(11), 856-863.
[PMID: 21960798]
Lavie, C.J.; McAuley, P.A.; Church, T.S.; Milani, R.V.; Blair, S.N. Obesity and cardiovascular diseases: Implications regarding fitness, fatness, and severity in the obesity paradox. J. Am. Coll. Cardiol., 2014, 63(14), 1345-1354.
[] [PMID: 24530666]
Kenchaiah, S.; Evans, J.C.; Levy, D.; Wilson, P.W.; Benjamin, E.J.; Larson, M.G.; Kannel, W.B.; Vasan, R.S. Obesity and the risk of heart failure. N. Engl. J. Med., 2002, 347(5), 305-313.
[] [PMID: 12151467]
Casati, A.; Putzu, M. Anesthesia in the obese patient: Pharmacokinetic considerations. J. Clin. Anesth., 2005, 17(2), 134-145.
[] [PMID: 15809132]
Seravalle, G.; Grassi, G. Sympathetic nervous system, hypertension, obesity and metabolic syndrome. High Blood Press. Cardiovasc. Prev., 2016, 23(3), 175-179.
[] [PMID: 26942609]
Lavie, C.J.; Milani, R.V.; Ventura, H.O. Obesity and cardiovascular disease: Risk factor, paradox, and impact of weight loss. J. Am. Coll. Cardiol., 2009, 53(21), 1925-1932.
[] [PMID: 19460605]
Lavie, C.J.; Alpert, M.A.; Arena, R.; Mehra, M.R.; Milani, R.V.; Ventura, H.O. Impact of obesity and the obesity paradox on prevalence and prognosis in heart failure. JACC Heart Fail., 2013, 1(2), 93-102.
[] [PMID: 24621833]
Ong, J.P.; Elariny, H.; Collantes, R.; Younoszai, A.; Chandhoke, V.; Reines, H.D.; Goodman, Z.; Younossi, Z.M. Predictors of nonalcoholic steatohepatitis and advanced fibrosis in morbidly obese patients. Obes. Surg., 2005, 15(3), 310-315.
[] [PMID: 15826462]
Farrell, G.C.; Teoh, N.C.; McCuskey, R.S. Hepatic microcirculation in fatty liver disease. Anat. Rec. (Hoboken), 2008, 291(6), 684-692.
[] [PMID: 18484615]
Iseki, K.; Ikemiya, Y.; Kinjo, K.; Inoue, T.; Iseki, C.; Takishita, S. Body mass index and the risk of development of end-stage renal disease in a screened cohort. Kidney Int., 2004, 65(5), 1870-1876.
[] [PMID: 15086929]
Hsu, C.Y.; McCulloch, C.E.; Iribarren, C.; Darbinian, J.; Go, A.S. Body mass index and risk for end-stage renal disease. Ann. Intern. Med., 2006, 144(1), 21-28.
[] [PMID: 16389251]
Ejerblad, E.; Fored, C.M.; Lindblad, P.; Fryzek, J.; McLaughlin, J.K.; Nyrén, O. Obesity and risk for chronic renal failure. J. Am. Soc. Nephrol., 2006, 17(6), 1695-1702.
[] [PMID: 16641153]
Speckman, R.A.; McClellan, W.M.; Volkova, N.V.; Jurkovitz, C.T.; Satko, S.G.; Schoolwerth, A.C.; Freedman, B.I. Obesity is associated with family history of ESRD in incident dialysis patients. Am. J. Kidney Dis., 2006, 48(1), 50-58.
[] [PMID: 16797386]
Wahba, I.M.; Mak, R.H. Obesity and obesity-initiated metabolic syndrome: Mechanistic links to chronic kidney disease. Clin. J. Am. Soc. Nephrol., 2007, 2(3), 550-562.
[] [PMID: 17699463]
Ramkumar, N.; Cheung, A.K.; Pappas, L.M.; Roberts, W.L.; Beddhu, S. Association of obesity with inflammation in chronic kidney disease: A cross-sectional study. J. Ren. Nutr., 2004, 14(4), 201-207.
[] [PMID: 15483779]
Wu, Y.; Liu, Z.; Xiang, Z.; Zeng, C.; Chen, Z.; Ma, X.; Li, L. Obesity-related glomerulopathy: Insights from gene expression profiles of the glomeruli derived from renal biopsy samples. Endocrinology, 2006, 147(1), 44-50.
[] [PMID: 16210374]
Chagnac, A.; Weinstein, T.; Korzets, A.; Ramadan, E.; Hirsch, J.; Gafter, U. Glomerular hemodynamics in severe obesity. Am. J. Physiol. Renal Physiol., 2000, 278(5), F817-F822.
[] [PMID: 10807594]
Bowman, S.L.; Hudson, S.A.; Simpson, G.; Munro, J.F.; Clements, J.A. A comparison of the pharmacokinetics of propranolol in obese and normal volunteers. Br. J. Clin. Pharmacol., 1986, 21(5), 529-532.
[] [PMID: 3718810]
Blouin, R.A.; Warren, G.W. Pharmacokinetic considerations in obesity. J. Pharm. Sci., 1999, 88(1), 1-7.
[] [PMID: 9874695]
Cheymol, G. Clinical pharmacokinetics of drugs in obesity. An update. Clin. Pharmacokinet., 1993, 25(2), 103-114.
[] [PMID: 8403734]
Cheymol, G. Effects of obesity on pharmacokinetics implications for drug therapy. Clin. Pharmacokinet., 2000, 39(3), 215-231.
[] [PMID: 11020136]
Shah, D.K.; Missmer, S.A.; Correia, K.F.; Ginsburg, E.S. Pharmacokinetics of human chorionic gonadotropin injection in obese and normal-weight women. J. Clin. Endocrinol. Metab., 2014, 99(4), 1314-1321.
[] [PMID: 24476082]
Gagnon-Auger, M.; du Souich, P.; Baillargeon, J.P.; Martin, E.; Brassard, P.; Ménard, J.; Ardilouze, J.L. Dose-dependent delay of the hypoglycemic effect of short-acting insulin analogs in obese subjects with type 2 diabetes: A pharmacokinetic and pharmacodynamic study. Diabetes Care, 2010, 33(12), 2502-2507.
[] [PMID: 20841613]
Wesolowski, C.A.; Wesolowski, M.J.; Babyn, P.S.; Wanasundara, S.N. Time varying apparent volume of distribution and drug half-lives following intravenous bolus injections. PLoS One, 2016, 11(7), e0158798.
[] [PMID: 27403663]
Abernethy, D.R.; Greenblatt, D.J.; Divoll, M.; Shader, R.I. Prolonged accumulation of diazepam in obesity. J. Clin. Pharmacol., 1983, 23(8-9), 369-376.
[] [PMID: 6415130]
Brill, M.J.; Houwink, A.P.; Schmidt, S.; Van Dongen, E.P.; Hazebroek, E.J.; van Ramshorst, B.; Deneer, V.H.; Mouton, J.W.; Knibbe, C.A. Reduced subcutaneous tissue distribution of cefazolin in morbidly obese versus non-obese patients determined using clinical microdialysis. J. Antimicrob. Chemother., 2014, 69(3), 715-723.
[] [PMID: 24214905]
Alexander, J.K.; Dennis, E.W.; Smith, W.G.; Amad, K.H.; Duncan, W.C.; Austin, R.C. Blood volume, cardiac output, and distribution of systemic blood flow in extreme obesity. Cardiovasc. Res. Cent. Bull., 1963, 1, 39-44.
[PMID: 14011956]
Horowitz, N.S.; Wright, A.A. Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies. Gynecol. Oncol., 2015, 138(1), 201-206.
[] [PMID: 25870918]
Kovesdy, C.P.; Furth, S.; Zoccali, C.; World Kidney Day Steering, C. Obesity and kidney disease: Hidden consequences of the epidemic. Indian J. Nephrol., 2017, 27(2), 85-92.
[] [PMID: 28356657]
van Rongen, A.; Välitalo, P.A.J.; Peeters, M.Y.M.; Boerma, D.; Huisman, F.W.; van Ramshorst, B.; van Dongen, E.P.A.; van den Anker, J.N.; Knibbe, C.A.J. Morbidly obese patients exhibit increased CYP2E1-mediated oxidation of acetaminophen. Clin. Pharmacokinet., 2016, 55(7), 833-847.
[] [PMID: 26818482]
de Hoogd, S.; Välitalo, P.A.J.; Dahan, A.; van Kralingen, S.; Coughtrie, M.M.W.; van Dongen, E.P.A.; van Ramshorst, B.; Knibbe, C.A.J. Influence of morbid obesity on the pharmacokinetics of morphine, morphine-3-glucuronide, and morphine-6-glucuronide. Clin. Pharmacokinet., 2017, 56(12), 1577-1587.
[] [PMID: 28510797]
Ferslew, B.C.; Johnston, C.K.; Tsakalozou, E.; Bridges, A.S.; Paine, M.F.; Jia, W.; Stewart, P.W.; Barritt, A.S., IV; Brouwer, K.L. Altered morphine glucuronide and bile acid disposition in patients with nonalcoholic steatohepatitis. Clin. Pharmacol. Ther., 2015, 97(4), 419-427.
[] [PMID: 25669174]
Zarezadeh, M.; Saedisomeolia, A.; Shekarabi, M.; Khorshidi, M.; Emami, M.R.; Müller, D.J. The effect of obesity, macronutrients, fasting and nutritional status on drug-metabolizing cytochrome P450s: A systematic review of current evidence on human studies. Eur. J. Nutr., 2021, 60(6), 2905-2921.
[] [PMID: 33141242]
Chiney, M.S.; Schwarzenberg, S.J.; Johnson, L.A. Altered xanthine oxidase and N-acetyltransferase activity in obese children. Br. J. Clin. Pharmacol., 2011, 72(1), 109-115.
[] [PMID: 21382071]
Balis, F.M. Pharmacokinetic drug interactions of commonly used anticancer drugs. Clin. Pharmacokinet., 1986, 11(3), 223-235.
[] [PMID: 2426030]
Nguyen, L.; Leger, F.; Lennon, S.; Puozzo, C. Intravenous busulfan in adults prior to haematopoietic stem cell transplantation: A population pharmacokinetic study. Cancer Chemother. Pharmacol., 2006, 57(2), 191-198.
[] [PMID: 16133536]
Gibbs, J.P.; Gooley, T.; Corneau, B.; Murray, G.; Stewart, P.; Appelbaum, F.R.; Slattery, J.T. The impact of obesity and disease on busulfan oral clearance in adults. Blood, 1999, 93(12), 4436-4440.
[] [PMID: 10361142]
Browning, B.; Thormann, K.; Donaldson, A.; Halverson, T.; Shinkle, M.; Kletzel, M. Busulfan dosing in children with BMIs ≥ 85% undergoing HSCT: A new optimal strategy. Biol. Blood Marrow Transplant., 2011, 17(9), 1383-1388.
[] [PMID: 21288495]
Ali, I.; Slizgi, J.R.; Kaullen, J.D.; Ivanovic, M.; Niemi, M.; Stewart, P.W.; Barritt, A.S., IV; Brouwer, K.L.R. Transporter-mediated alterations in patients with NASH increase systemic and hepatic exposure to an OATP and MRP2 substrate. Clin. Pharmacol. Ther., 2017. [Epub ahead of print].
[PMID: 29271075]
Thompson, P.A.; Rosner, G.L.; Matthay, K.K.; Moore, T.B.; Bomgaars, L.R.; Ellis, K.J.; Renbarger, J.; Berg, S.L. Impact of body composition on pharmacokinetics of doxorubicin in children: A glaser pediatric research network study. Cancer Chemother. Pharmacol., 2009, 64(2), 243-251.
[] [PMID: 19020877]
Powis, G.; Reece, P.; Ahmann, D.L.; Ingle, J.N. Effect of body weight on the pharmacokinetics of cyclophosphamide in breast cancer patients. Cancer Chemother. Pharmacol., 1987, 20(3), 219-222.
[] [PMID: 3315280]
Ritzmo, C.; Söderhäll, S.; Karlén, J.; Nygren, H.; Eksborg, S. Pharmacokinetics of doxorubicin and etoposide in a morbidly obese pediatric patient. Pediatr. Hematol. Oncol., 2007, 24(6), 437-445.
[] [PMID: 17710661]
Stocker, G.; Hacker, U.T.; Fiteni, F.; John Mahachie, J.; Roth, A.D.; Van Cutsem, E.; Peeters, M.; Lordick, F.; Mauer, M. Clinical consequences of chemotherapy dose reduction in obese patients with stage III colon cancer: A retrospective analysis from the PETACC 3 study. Eur. J. Cancer, 2018, 99, 49-57.
[] [PMID: 29906734]
Chiou, W.L. The physiological significance of total body clearance in pharmacokinetic studies. J. Clin. Hosp. Pharm., 1982, 7(1), 25-30.
[] [PMID: 7096575]
Janson, B.; Thursky, K. Dosing of antibiotics in obesity. Curr. Opin. Infect. Dis., 2012, 25(6), 634-649.
[] [PMID: 23041773]
Ribstein, J.; du Cailar, G.; Mimran, A. Combined renal effects of overweight and hypertension. Hypertension, 1995, 26(4), 610-615.
[] [PMID: 7558220]
NIH. NKEDP CKD and Drug Dosing: Information for Providers. Available from: drug-dosing-providers (Accessed: April 26, 2021).
Wuerzner, G.; Bochud, M.; Giusti, V.; Burnier, M. Measurement of glomerular filtration rate in obese patients: Pitfalls and potential consequences on drug therapy. Obes. Facts, 2011, 4(3), 238-243.
[] [PMID: 21701241]
Meng, L.; Mui, E.; Holubar, M.K.; Deresinski, S.C. Comprehensive guidance for antibiotic dosing in obese adults. Pharmacotherapy, 2017, 37(11), 1415-1431.
[] [PMID: 28869666]
Adane, E.D.; Herald, M.; Koura, F. Pharmacokinetics of vancomycin in extremely obese patients with suspected or confirmed Staphylococcus aureus infections. Pharmacotherapy, 2015, 35(2), 127-139.
[] [PMID: 25644478]
Pan, Y.; He, X.; Yao, X.; Yang, X.; Wang, F.; Ding, X.; Wang, W. The effect of body mass index and creatinine clearance on serum trough concentration of vancomycin in adult patients. BMC Infect. Dis., 2020, 20(1), 341.
[] [PMID: 32404057]
Alobaid, A.S.; Wallis, S.C.; Jarrett, P.; Starr, T.; Stuart, J.; Lassig-Smith, M.; Mejia, J.L.; Roberts, M.S.; Roger, C.; Udy, A.A.; Lipman, J.; Roberts, J.A. Population pharmacokinetics of piperacillin in nonobese, obese, and morbidly obese critically ill patients. Antimicrob. Agents Chemother., 2017, 61(3), e01276-16.
[] [PMID: 28052849]
Hites, M.; Taccone, F.S.; Wolff, F.; Maillart, E.; Beumier, M.; Surin, R.; Cotton, F.; Jacobs, F. Broad-spectrum β-lactams in obese non-critically ill patients. Nutr. Diabetes, 2014, 4(6), e119.
[] [PMID: 24956136]
Hites, M.; Taccone, F.S.; Wolff, F.; Cotton, F.; Beumier, M.; De Backer, D.; Roisin, S.; Lorent, S.; Surin, R.; Seyler, L.; Vincent, J.L.; Jacobs, F. Case-control study of drug monitoring of β-lactams in obese critically ill patients. Antimicrob. Agents Chemother., 2013, 57(2), 708-715.
[] [PMID: 23147743]
Prado, C.M.; Lima, I.S.; Baracos, V.E.; Bies, R.R.; McCargar, L.J.; Reiman, T.; Mackey, J.R.; Kuzma, M.; Damaraju, V.L.; Sawyer, M.B. An exploratory study of body composition as a determinant of epirubicin pharmacokinetics and toxicity. Cancer Chemother. Pharmacol., 2011, 67(1), 93-101.
[] [PMID: 20204364]
Lundqvist, E.A.; Fujiwara, K.; Seoud, M. Principles of chemotherapy. Int. J. Gynaecol. Obstet., 2015, 131(Suppl. 2), S146-S149.
[] [PMID: 26433671]
Livshits, Z.; Rao, R.B.; Smith, S.W. An approach to chemotherapy-associated toxicity. Emerg. Med. Clin. North Am., 2014, 32(1), 167-203.
[] [PMID: 24275174]
Dickens, E.; Ahmed, S. Principles of cancer treatment by chemotherapy. Surgery, 2018, 36(3), 134-138.
Goodman, L.S.; Gilman, A. Goodman & Gilman’s the pharmacological basis of therapeutics; McGraw-Hill: New York, 2006.
Lipinski, C.A. Drug-like properties and the causes of poor solubility and poor permeability. J. Pharmacol. Toxicol. Methods, 2000, 44(1), 235-249.
[] [PMID: 11274893]
Fisusi, F.A.; Akala, E.O. Drug combinations in breast cancer therapy. Pharm. Nanotechnol., 2019, 7(1), 3-23.
[] [PMID: 30666921]
Li, S.; Jiang, M.; Wang, L.; Yu, S. Combined chemotherapy with cyclooxygenase-2 (COX-2) inhibitors in treating human cancers: Recent advancement. Biomed. Pharmacother., 2020, 129, 110389.
[] [PMID: 32540642]
Bagchi, S.; Yuan, R.; Engleman, E.G. Immune checkpoint inhibitors for the treatment of cancer: Clinical impact and mechanisms of response and resistance. Annu. Rev. Pathol., 2021, 16(1), 223-249.
[] [PMID: 33197221]
Marin-Acevedo, J.A.; Kimbrough, E.O.; Lou, Y. Next generation of immune checkpoint inhibitors and beyond. J. Hematol. Oncol., 2021, 14(1), 45.
[] [PMID: 33741032]
Frasca, D.; Diaz, A.; Romero, M.; Thaller, S.; Blomberg, B.B. Secretion of autoimmune antibodies in the human subcutaneous adipose tissue. PLoS One, 2018, 13(5), e0197472.
[] [PMID: 29768501]
Dyck, L.; Prendeville, H.; Raverdeau, M.; Wilk, M.M.; Loftus, R.M.; Douglas, A.; McCormack, J.; Moran, B.; Wilkinson, M.; Mills, E.L.; Doughty, M.; Fabre, A.; Heneghan, H.; LeRoux, C.; Hogan, A.; Chouchani, E.T.; O’Shea, D.; Brennan, D.; Lynch, L. Suppressive effects of the obese tumor microenvironment on CD8 T cell infiltration and effector function. J. Exp. Med., 2022, 219(3), e20210042.
[] [PMID: 35103755]
An, Y.; Wu, Z.; Wang, N.; Yang, Z.; Li, Y.; Xu, B.; Sun, M. Association between body mass index and survival outcomes for cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis. J. Transl. Med., 2020, 18(1), 235.
[] [PMID: 32532255]
Xu, H.; Cao, D.; He, A.; Ge, W. The prognostic role of obesity is independent of sex in cancer patients treated with immune checkpoint inhibitors: A pooled analysis of 4090 cancer patients. Int. Immunopharmacol., 2019, 74(1), 105745.
[] [PMID: 31302449]
Wang, Z.; Aguilar, E.G.; Luna, J.I.; Dunai, C.; Khuat, L.T.; Le, C.T.; Mirsoian, A.; Minnar, C.M.; Stoffel, K.M.; Sturgill, I.R.; Grossenbacher, S.K.; Withers, S.S.; Rebhun, R.B.; Hartigan-O’Connor, D.J.; Méndez-Lagares, G.; Tarantal, A.F.; Isseroff, R.R.; Griffith, T.S.; Schalper, K.A.; Merleev, A.; Saha, A.; Maverakis, E.; Kelly, K.; Aljumaily, R.; Ibrahimi, S.; Mukherjee, S.; Machiorlatti, M.; Vesely, S.K.; Longo, D.L.; Blazar, B.R.; Canter, R.J.; Murphy, W.J.; Monjazeb, A.M. Paradoxical effects of obesity on T cell function during tumor progression and PD-1 checkpoint blockade. Nat. Med., 2019, 25(1), 141-151.
[] [PMID: 30420753]
Ryman, J.T.; Meibohm, B. Pharmacokinetics of monoclonal antibodies. CPT Pharmacometrics Syst. Pharmacol., 2017, 6(9), 576-588.
[] [PMID: 28653357]
FDA. Estimating the maximum safe starting dose in initial clinical trials for therapeutics in adult healthy volunteers. 2005. Available from: (Accessed: March 6, 2022).
FDA. Highlights of prescribing information. KEYTRUDA® (pembrolizumab) injection, for intravenous use Initial U.S. Approval: 2014. 2014. Available from: (Accessed: March 6, 2022).
Wang, D.D.; Zhang, S.; Zhao, H.; Men, A.Y.; Parivar, K. Fixed dosing versus body size-based dosing of monoclonal antibodies in adult clinical trials. J. Clin. Pharmacol., 2009, 49(9), 1012-1024.
[] [PMID: 19620385]
Zhang, S.; Shi, R.; Li, C.; Parivar, K.; Wang, D.D. Fixed dosing versus body size-based dosing of therapeutic peptides and proteins in adults. J. Clin. Pharmacol., 2012, 52(1), 18-28.
[] [PMID: 21233304]
Ahamadi, M.; Freshwater, T.; Prohn, M.; Li, C.H.; de Alwis, D.P.; de Greef, R.; Elassaiss-Schaap, J.; Kondic, A.; Stone, J.A. Model-based characterization of the pharmacokinetics of pembrolizumab: A humanized anti-PD-1 monoclonal antibody in advanced solid tumors. CPT Pharmacometrics Syst. Pharmacol., 2017, 6(1), 49-57.
[] [PMID: 27863186]
Hendrikx, J.J.M.A.; Haanen, J.B.A.G.; Voest, E.E.; Schellens, J.H.M.; Huitema, A.D.R.; Beijnen, J.H. Fixed dosing of monoclonal antibodies in oncology. Oncologist, 2017, 22(10), 1212-1221.
[] [PMID: 28754722]
Pinkel, D. The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res., 1958, 18(7), 853-856.
[PMID: 13573353]
Sawyer, M.; Ratain, M.J. Body surface area as a determinant of pharmacokinetics and drug dosing. Invest. New Drugs, 2001, 19(2), 171-177.
[] [PMID: 11392451]
Field, K.M.; Kosmider, S.; Jefford, M.; Michael, M.; Jennens, R.; Green, M.; Gibbs, P. Chemotherapy dosing strategies in the obese, elderly, and thin patient: Results of a nationwide survey. J. Oncol. Pract., 2008, 4(3), 108-113.
[] [PMID: 20856612]
Carroll, J.P.; Protani, M.M.; Nguyen, L.; Cheng, M.E.; Fay, M.; Saleem, M.; Pillay, P.S.; Walpole, E.; Martin, J.H. Toxicity and tolerability of adjuvant breast cancer chemotherapy in obese women. Med. Oncol., 2014, 31(4), 881.
[] [PMID: 24549982]
Chambers, P.; Daniels, S.H.; Thompson, L.C.; Stephens, R.J. Chemotherapy dose reductions in obese patients with colorectal cancer. Ann. Oncol., 2012, 23(3), 748-753.
[] [PMID: 21652579]
Chan, H.; Jackson, S.; McLay, J.; Knox, A.; Lee, J.; Wang, S.; Issa, S. Obese non-Hodgkin lymphoma patients tolerate full uncapped doses of chemotherapy with no increase in toxicity, and a similar survival to that seen in nonobese patients. Leuk. Lymphoma, 2016, 57(11), 2584-2592.
[] [PMID: 26943235]
Furlanetto, J.; Eiermann, W.; Marmé, F.; Reimer, T.; Reinisch, M.; Schmatloch, S.; Stickeler, E.; Thomssen, C.; Untch, M.; Denkert, C.; von Minckwitz, G.; Lederer, B.; Nekljudova, V.; Weber, K.; Loibl, S.; Möbus, V. Higher rate of severe toxicities in obese patients receiving dose- dense (dd) chemotherapy according to unadjusted body surface area: Results of the prospectively randomized GAIN study. Ann. Oncol., 2016, 27(11), 2053-2059.
[] [PMID: 27502721]
Ganti, A.; Liu, W.; Luo, S.; Sanfilippo, K.M.; Roop, R.; Lynch, R.; Riedell, P.; O’Brian, K.; Colditz, G.A.; Carson, K.R. Impact of body mass index on incidence of febrile neutropenia and treatment-related mortality in United States veterans with diffuse large B-cell lymphoma receiving rituximab, cyclophosphamide, doxorubicin, vincristine, prednisone. Br. J. Haematol., 2014, 167(5), 699-702.
[] [PMID: 25040880]
Hansen, J.; Stephan, J.M.; Freesmeier, M.; Bender, D.; Button, A.; Goodheart, M.J. The effect of weight-based chemotherapy dosing in a cohort of gynecologic oncology patients. Gynecol. Oncol., 2015, 138(1), 154-158.
[] [PMID: 25958318]
Kamimura, K.; Matsumoto, Y.; Zhou, Q.; Moriyama, M.; Saijo, Y. Myelosuppression by chemotherapy in obese patients with gynecological cancers. Cancer Chemother. Pharmacol., 2016, 78(3), 633-641.
[] [PMID: 27485538]
Lote, H.; Sharp, A.; Redana, S.; Papadimitraki, E.; Capelan, M.; Ring, A. Febrile neutropenia rates according to body mass index and dose capping in women receiving chemotherapy for early breast cancer. Clin. Oncol. (R. Coll. Radiol.), 2016, 28(9), 597-603.
[] [PMID: 26936608]
Morrison, V.A.; McCall, L.; Muss, H.B.; Jatoi, A.; Cohen, H.J.; Cirrincione, C.T.; Ligibel, J.A.; Lafky, J.M.; Hurria, A. The impact of actual body weight-based chemotherapy dosing and body size on adverse events and outcome in older patients with breast cancer: Results from Cancer and Leukemia Group B (CALGB) trial 49907 (Alliance A151436). J. Geriatr. Oncol., 2018, 9(3), 228-234.
[] [PMID: 29233548]
Robins, H.I.; Eickhoff, J.; Gilbert, M.R.; Armstrong, T.S.; Shi, W.; De Groot, J.F.; Schultz, C.J.; Hunter, G.K.; Valeinis, E.; Roach, M., III; Youssef, E.F.; Souhami, L.; Howard, S.P.; Lieberman, F.S.; Herman, J.G.; Zhang, P.; Mehta, M.P. The association between BMI and BSA-temozolomide-induced myelosuppression toxicities: A correlative analysis of NRG oncology RTOG 0525. Neurooncol. Pract., 2019, 6(6), 473-478.
[] [PMID: 31832217]
Hourdequin, K.C.; Schpero, W.L.; McKenna, D.R.; Piazik, B.L.; Larson, R.J. Toxic effect of chemotherapy dosing using actual body weight in obese versus normal-weight patients: A systematic review and meta-analysis. Ann. Oncol., 2013, 24(12), 2952-2962.
[] [PMID: 23965736]
Lyman, G.H.; Dale, D.C.; Crawford, J. Incidence and predictors of low dose-intensity in adjuvant breast cancer chemotherapy: A nationwide study of community practices. J. Clin. Oncol., 2003, 21(24), 4524-4531.
[] [PMID: 14673039]
Griggs, J.J.; Sabel, M.S. Obesity and cancer treatment: Weighing the evidence. J. Clin. Oncol., 2008, 26(25), 4060-4062.
[] [PMID: 18757320]
Griggs, J.J.; Sorbero, M.E.; Lyman, G.H. Undertreatment of obese women receiving breast cancer chemotherapy. Arch. Intern. Med., 2005, 165(11), 1267-1273.
[] [PMID: 15956006]
Lyman, G.H. Impact of chemotherapy dose intensity on cancer patient outcomes. J. Natl. Compr. Canc. Netw., 2009, 7(1), 99-108.
[] [PMID: 19176210]
Lyman, G.H.; Dale, D.C.; Friedberg, J.; Crawford, J.; Fisher, R.I. Incidence and predictors of low chemotherapy dose-intensity in aggressive non-Hodgkin’s lymphoma: A nationwide study. J. Clin. Oncol., 2004, 22(21), 4302-4311.
[] [PMID: 15381684]
Wu, W.; Liu, X.; Chaftari, P.; Cruz Carreras, M.T.; Gonzalez, C.; Viets-Upchurch, J.; Merriman, K.; Tu, S.M.; Dalal, S.; Yeung, S.C. Association of body composition with outcome of docetaxel chemotherapy in metastatic prostate cancer: A retrospective review. PLoS One, 2015, 10(3), e0122047.
[] [PMID: 25822612]
Gurney, H. Dose calculation of anticancer drugs: A review of the current practice and introduction of an alternative. J. Clin. Oncol., 1996, 14(9), 2590-2611.
[] [PMID: 8823340]
Sparreboom, A.; Verweij, J. Advances in cancer therapeutics. Clin. Pharmacol. Ther., 2009, 85(2), 113-117.
[] [PMID: 19151631]
Felici, A.; Verweij, J.; Sparreboom, A. Dosing strategies for anticancer drugs: The good, the bad and body-surface area. Eur. J. Cancer, 2002, 38(13), 1677-1684.
[] [PMID: 12175683]
Du Bois, D.; Du Bois, E.F. A formula to estimate the approximate surface area if height and weight be known. 1916. Nutrition, 1989, 5(5), 303-311.
[PMID: 2520314]
Yu, C.Y.; Lo, Y.H.; Chiou, W.K. The 3D scanner for measuring body surface area: A simplified calculation in the Chinese adult. Appl. Ergon., 2003, 34(3), 273-278.
[] [PMID: 12737928]
Bouleftour, W.; Mery, B.; Chanal, E.; Rowinski, E.; Viard, A.; Forges, F.; Fournel, P.; Rivoirard, R. Obesity and chemotherapy administration: Between empiric and mathematic method review. Acta Oncol., 2019, 58(6), 880-887.
[] [PMID: 30907190]
Redlarski, G.; Palkowski, A.; Krawczuk, M. Body surface area formulae: An alarming ambiguity. Sci. Rep., 2016, 6(1), 27966.
[] [PMID: 27323883]
Calvert, A.H.; Newell, D.R.; Gumbrell, L.A.; O’Reilly, S.; Burnell, M.; Boxall, F.E.; Siddik, Z.H.; Judson, I.R.; Gore, M.E.; Wiltshaw, E. Carboplatin dosage: Prospective evaluation of a simple formula based on renal function. J. Clin. Oncol., 1989, 7(11), 1748-1756.
[] [PMID: 2681557]
Duffull, S.B.; Robinson, B.A. Clinical pharmacokinetics and dose optimisation of carboplatin. Clin. Pharmacokinet., 1997, 33(3), 161-183.
[] [PMID: 9314610]
Latz, J.E.; Chaudhary, A.; Ghosh, A.; Johnson, R.D. Population pharmacokinetic analysis of ten phase II clinical trials of pemetrexed in cancer patients. Cancer Chemother. Pharmacol., 2006, 57(4), 401-411.
[] [PMID: 16322991]
Chatelut, E.; Puisset, F. The scientific basis of body surface area-based dosing. Clin. Pharmacol. Ther., 2014, 95(4), 359-361.
[] [PMID: 24646485]
Ekhart, C.; Rodenhuis, S.; Schellens, J.H.; Beijnen, J.H.; Huitema, A.D. Carboplatin dosing in overweight and obese patients with normal renal function, does weight matter? Cancer Chemother. Pharmacol., 2009, 64(1), 115-122.
[] [PMID: 18989671]
De Jonge, M.E.; Mathôt, R.A.; Van Dam, S.M.; Beijnen, J.H.; Rodenhuis, S. Extremely high exposures in an obese patient receiving high-dose cyclophosphamide, thiotepa and carboplatin. Cancer Chemother. Pharmacol., 2002, 50(3), 251-255.
[] [PMID: 12203108]
Haak, H.R.; Hermans, J.; van de Velde, C.J.; Lentjes, E.G.; Goslings, B.M.; Fleuren, G.J.; Krans, H.M. Optimal treatment of adrenocortical carcinoma with mitotane: Results in a consecutive series of 96 patients. Br. J. Cancer, 1994, 69(5), 947-951.
[] [PMID: 8180029]
van Slooten, H.; Moolenaar, A.J.; van Seters, A.P.; Smeenk, D. The treatment of adrenocortical carcinoma with o,p′-DDD: Prognostic implications of serum level monitoring. Eur. J. Cancer Clin. Oncol., 1984, 20(1), 47-53.
[] [PMID: 6537915]
Bouleftour, W.; Viard, A.; Mery, B.; Chaux, R.; Magne, N.; Simoens, X.; Rivoirard, R.; Forges, F. Body surface area capping may not improve cytotoxic drugs tolerance. Sci. Rep., 2021, 11(1), 2431.
[] [PMID: 33510207]
Griggs, J.J.; Mangu, P.B.; Temin, S.; Lyman, G.H. Appropriate chemotherapy dosing for obese adult patients with cancer: American society of clinical oncology clinical practice guideline. J. Oncol. Pract., 2012, 8(4), e59-e61.
[] [PMID: 29452546]
Griggs, J.J.; Culakova, E.; Sorbero, M.E.; van Ryn, M.; Poniewierski, M.S.; Wolff, D.A.; Crawford, J.; Dale, D.C.; Lyman, G.H. Effect of patient socioeconomic status and body mass index on the quality of breast cancer adjuvant chemotherapy. J. Clin. Oncol., 2007, 25(3), 277-284.
[] [PMID: 17159190]
Fancher, K.M.; Sacco, A.J.; Gwin, R.C.; Gormley, L.K.; Mitchell, C.B. Comparison of two different formulas for body surface area in adults at extremes of height and weight. J. Oncol. Pharm. Pract., 2016, 22(5), 690-695.
[] [PMID: 26385906]
de Man, F.M.; Veerman, G.D.M.; Oomen-de Hoop, E.; Deenen, M.J.; Meulendijks, D.; Mandigers, C.M.P.W.; Soesan, M.; Schellens, J.H.M.; van Meerten, E.; van Gelder, T.; Mathijssen, R.H.J. Comparison of toxicity and effectiveness between fixed-dose and body surface area-based dose capecitabine. Ther. Adv. Med. Oncol., 2019, 11, 1758835919838964.
[] [PMID: 31019570]
Eaton, K. D.; Lyman, P. H. Dosing of anticancer agents in adults. UpToDate, 2021. Available from:
Hijiya, N.; Panetta, J.C.; Zhou, Y.; Kyzer, E.P.; Howard, S.C.; Jeha, S.; Razzouk, B.I.; Ribeiro, R.C.; Rubnitz, J.E.; Hudson, M.M.; Sandlund, J.T.; Pui, C.H.; Relling, M.V. Body mass index does not influence pharmacokinetics or outcome of treatment in children with acute lymphoblastic leukemia. Blood, 2006, 108(13), 3997-4002.
[] [PMID: 16917005]
Kendrick, J.G.; Carr, R.R.; Ensom, M.H. Pharmacokinetics and drug dosing in obese children. J. Pediatr. Pharmacol. Ther., 2010, 15(2), 94-109.
[] [PMID: 22477800]
Ceja, M.E.; Christensen, A.M. Dosing considerations in pediatric oncology. US Pharm., 2013, 38, 8-11.
Behan, J.W.; Yun, J.P.; Proektor, M.P.; Ehsanipour, E.A.; Arutyunyan, A.; Moses, A.S.; Avramis, V.I.; Louie, S.G.; Butturini, A.; Heisterkamp, N.; Mittelman, S.D. Adipocytes impair leukemia treatment in mice. Cancer Res., 2009, 69(19), 7867-7874.
[] [PMID: 19773440]
Lange, B.J.; Gerbing, R.B.; Feusner, J.; Skolnik, J.; Sacks, N.; Smith, F.O.; Alonzo, T.A. Mortality in overweight and underweight children with acute myeloid leukemia. JAMA, 2005, 293(2), 203-211.
[] [PMID: 15644547]
Dobbs, N.A.; Twelves, C.J.; Gillies, H.; James, C.A.; Harper, P.G.; Rubens, R.D. Gender affects doxorubicin pharmacokinetics in patients with normal liver biochemistry. Cancer Chemother. Pharmacol., 1995, 36(6), 473-476.
[] [PMID: 7554038]
Pfreundschuh, M.; Müller, C.; Zeynalova, S.; Kuhnt, E.; Wiesen, M.H.; Held, G.; Rixecker, T.; Poeschel, V.; Zwick, C.; Reiser, M.; Schmitz, N.; Murawski, N. Suboptimal dosing of rituximab in male and female patients with DLBCL. Blood, 2014, 123(5), 640-646.
[] [PMID: 24297867]
Gérard, S.; Bréchemier, D.; Lefort, A.; Lozano, S.; Abellan Van Kan, G.; Filleron, T.; Mourey, L.; Bernard-Marty, C.; Rougé-Bugat, M.E.; Soler, V.; Vellas, B.; Cesari, M.; Rolland, Y.; Balardy, L. Body composition and anti-neoplastic treatment in adult and older subjects - a systematic review. J. Nutr. Health Aging, 2016, 20(8), 878-888.
[] [PMID: 27709238]
Zuccaro, P.; Guandalini, S.; Pacifici, R.; Pichini, S.; Di Martino, L.; Guiducci, M.; Giuliano, M.; Di Tullio, M.T.; Pettoello Mantovani, M. Fat body mass and pharmacokinetics of oral 6-mercaptopurine in children with acute lymphoblastic leukemia. Ther. Drug Monit., 1991, 13(1), 37-41.
[] [PMID: 2057989]
Seo, J.W.; Fu, K.; Correa, S.; Eisenstein, M.; Appel, E.A.; Soh, H.T. Real-time monitoring of drug pharmacokinetics within tumor tissue in live animals. Sci. Adv., 2022, 8(1), eabk2901.
[] [PMID: 34995112]
MacDonald, J.J.; Moore, J.; Davey, V.; Pickering, S.; Dunne, T. The weight debate. J. Intensive Care Soc., 2015, 16(3), 234-238.
[] [PMID: 28979416]
Peterson, C.M.; Thomas, D.M.; Blackburn, G.L.; Heymsfield, S.B. Universal equation for estimating ideal body weight and body weight at any BMI. Am. J. Clin. Nutr., 2016, 103(5), 1197-1203.
[] [PMID: 27030535]

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