Chemotherapy Dosing Part I: Scientific Basis for Current Practice and Use of Body Surface Area

Abstract

Cytotoxic chemotherapy is characterised by a low therapeutic index and significant variability in therapeutic and toxic effects. In an attempt to reduce this variability, most chemotherapy doses are individualised according to patient body surface area (BSA). This practice, which was introduced almost 50 years ago, clearly has practical and economic implications for the healthcare system. Furthermore, the clinical value of this approach has, in recent years, been questioned. Despite established practice, chemotherapy dose selection remains complicated, partly because treatment effects are difficult to measure, partly because drugs are used in combination with other treatment modalities, and also because the patient's condition may change with disease progression. Various patient-related factors can affect drug pharmacokinetics (PK) and pharmacodynamics (PD), for example organ function, expression and activity of metabolising enzymes, drug resistance, body size, gender, age, concomitant disease and co-administration of other drugs. These factors may be of clinical significance in chemotherapy dose determination and measures of PK, PD or both feature in attempts to devise more rigorous methods for chemotherapy dosing. Part I of this series of two reviews describes the history and clinical impact of BSA-based chemotherapy, and examines the scientific evidence to support BSA dosing. It evaluates the factors affecting PK and PD for specific drugs that could inform and refine dose determination.

Impact of sarcopenia in borderline resectable and locally advanced pancreatic cancer patients receiving stereotactic body radiation therapy

“…Specifically, body mass index (BMI) has been widely evaluated due to its ability to normalize for patient height (9)(10)(11)(12)(13)(14). Another metric, body surface area (BSA), has been incorporated clinically to personalize chemotherapeutic doses based on patient size and visceral fat content (15)(16)(17). A relatively new metric, total psoas area (TPA), has shown promise as an additional proxy for nutritional status; specifically, low TPA, or sarcopenia, has been used in place of deficient nutritional status in gastrointestinal cancers (18,19).…”

Outcomes after autologous SCT in lymphoma patients grouped by weight

“…1 Medication pharmacokinetics are altered in obese patients, largely due to increased adipose tissue, various comorbidities and altered organ function, leading to differences in volume of distribution, drug clearance and protein binding. 2,3 Cytotoxic chemotherapy is traditionally dosed using body surface area or body weight; however, in this era of increasing obesity, clinicians are hesitant to use actual body weight to calculate chemotherapy doses because of concerns of overdose and the potential for severe toxicity. 4 These concerns have led to practices such as dose capping body surface area at a maximum of 2 m 2 , or using ideal or adjusted body weight in weight-based dosing of obese patients.…”

Utility of Limited Sampling Strategies for Anticancer Agents in the Clinical Arena: A Systematic Review

“…Clinicians routinely estimate doses of anticancer agents by multiplying a patient's BSA by a standard dose in mg/m 2 . These standard doses of many anticancer agents have been calculated using the DuBois and DuBois equation [BSA (m2) = weight(kg) 0.425 x height(cm) 0.725 x 0.007184] [72,73]. This Abbreviations: 5-FU = 5-Fluorouracil; 95% CI = 95% confidence interval; ALL = acute lymphoblastic leukemia; AML = acute myeloid leukemia; ANLL = acute non-lymphocytic leukemia AUC = area under the concentration-time curve; BMT = bone marrow transplant; CI = confidence interval; Cmax = maximum concentration; CMF = chemotherapy combination with CY, MTX and 5-FU; CML = chronic myeloid leukemia; Cn=concentration at n time in hours unless specified otherwise; CPT-11 = irinotecan; Css = concentration at steady state; CV = coefficient of variation; CY = cyclophosphamide; DTIC = dacarbazine; EOI = end of infusion; h = hour; G-CSF= granulocyte-colony stimulating factor; IQR = interquartile range LSS = limited sampling strategy; MAE = mean absolute error; ME = mean prediction error; MTIC = active metabolite of temozolamide (methyl triazene); MTX = methotrexate; N/A = not available; PK = pharmacokinetic; SC= subcutaneously; SEM = standard error of mean; SN-38 = active metabolite of irinotecan r = correlation coefficient; r 2 = coefficient of determination; RMSE = root mean squared prediction error; VDS1= first validation data set; VDS2= second validation data set; VP-16 = etoposide equation was derived with data from 9 human molds and gained favor because the equation exhibited the least amount of variability (+ 5%) when compared to the weight-basedMeeh's formula [65,66].…”