The predictive value of body protein for chemotherapy-induced toxicity

Abstract

BACKGROUND The use of body surface area in determining chemotherapy dosing, particularly in the obese, remains controversial. Total body nitrogen (TBN) measurement in patients with serious illness has been suggested to be an accurate predictor of clinical course. The ability of TBN to predict chemotherapy‐induced neutropenia was examined in the current study. METHODS TBN measurements were performed in 31 female outpatients with breast carcinoma who were undergoing standard cyclophosphamide, methotrexate, and 5‐fluorouracil (CMF)‐based chemotherapy (median age, 48 years; range, 26– 77 years). TBN was measured using the in vivo neutron capture analysis technique on Day 1 of Cycles 2–6. The chemotherapy toxicity index used was the absolute neutrophil count nadir (ANCN). Neutropenia was defined as an ANCN < 1.0 × 109/L. The nitrogen index (NI) (TBN expressed as a percentage of age‐, gender‐. and height‐matched healthy patients) then was compared with the corresponding ANCN values. RESULTS Using receiver operating characteristics analysis, a “cut‐off” value of NI = 0.89 was found. In this group of patients, when the NI was < 0.89, 11 of 13 courses in 7 patients (85%) led to an ANCN of < 1.0 × 109/L, and when the NI was > 0.89, 29 of 109 courses (27%) led to an ANCN of < 1.0 × 109/L (P < 0.0001). CONCLUSIONS In this small group of breast carcinoma patients, the NI was found to be the most powerful predictor of neutropenia after CMF‐based chemotherapy. The authors conclude that NI may be a useful clinical tool in identifying patients at a higher risk of chemotherapy‐induced toxicity when widely distributed drug combinations such as CMF are used, and warrants further study with other commonly used drugs or drug regimens. Cancer 2000;88:796–803. © 2000 American Cancer Society.

Body Composition as an Independent Determinant of 5-Fluorouracil–Based Chemotherapy Toxicity

“…They found a 28-fold increase in the relative risk of grade 3/4 neutropenia in multivariate analysis if a patient's LBM was <89% of age and sex-adjusted norms. Although methods of body composition analysis (whole-body nitrogen counting) and units of expression of the data were different in the study of Aslani et al (6) than those used here, the overall conclusions of our studies are identical.…”

“…Furthermore, differences in toxicity between men and women with respect to 5-FU may be due to differences in LBM. Our study and previous research (6,9) suggest that 5-FU dose normalization to LBM may be a better way to individualize 5-FU chemotherapy and therefore prevent excess toxicity than the current convention of normalizing the dose to BSA. This concept awaits verification through prospective testing of drug dosing schedules per kilogram LBM.…”

“…Aslani et al (6) studied 31 patients treated with cyclophosphamide, methotrexate, and 5-FU chemotherapy using BSA dosing. They found a 28-fold increase in the relative risk of grade 3/4 neutropenia in multivariate analysis if a patient's LBM was <89% of age and sex-adjusted norms.…”

Usefulness of a pharmacist outpatient service for S-1 adjuvant chemotherapy in patients with gastric cancer

“…Therefore, in the present study it was considered that absorption abnormalities may affect the blood concentration of the drug (3,8). In addition, weight loss due to a decrease in postoperative oral intake is likely to reduce muscle mass, which may also affect blood drug levels (21)(22)(23)(24). Therefore, the concentration of drug in the blood would exceed the therapeutic index resulting in an increase in AEs, which may lead to subsequent non-adherence.…”

Perioperative Correction of Metabolism in Patients with Lung Cancer

“…Источники эндогенного азота при антигипоксической терапии могут включаться в реакции ресинтеза белко вых молекул и не выводиться почками, что может спо собствовать сокращению сроков отрицательного азотис того баланса, опасного с точки зрения развития послеоперационных осложнений и продолжения проти воопухолевой терапии [32,33]. Сохранение белково энергетического баланса в онкологии играет важную роль в проведении последующих этапов лечения онко логических больных: у истощенных больных чаще воз никают побочные эффекты от проводимого лечения, они плохо отвечают на химиотерапию, долго находятся на стационарном химиотерапевтическом лечении, в этой группе больных раком легкого отмечается низкая выжи ваемость [34][35][36][37]. Выявленные положительные эффек ты цитофлавина у онкопульмонологических больных подчеркивают значимую роль гипоксических процессов в формировании синдрома гиперкатаболизма гиперме таболизма и зависимость сроков их купирования от включения антигипоксантов в комплекс послеопераци онной интенсивной терапии.…”