Among the factors that can affect a drug’s distribution are body water and fat composition. Alterations in either of these parameters can impact drug toxicity. Little is known, however, about the effect that body composition has on chemotherapy toxicity in women being treated for BC. Such knowledge would be essential for oncologic pharmacists to assist in making dosing recommendations.

Investigators performed a systematic review examining the impact of body composition on chemotherapy toxicity in women who are being treated for BC. In particular, the researchers sought to determine the association of low lean body mass (LBM) on both hematologic and nonhematologic chemotherapy toxicity. They also wanted to assess whether there was an association between abdominal adipose tissue and chemotherapy toxicity.

Four databases (Pub Med, Scopus, CINAHL, and the Cochrane Central Register of Controlled Trials) were searched in November 2021. Inclusion criteria were studies involving either adult women with BC only, or if other diseases were included the studies had to contain stratified data to separately include women with BC. Body composition had to be assessed prior to chemotherapy using CT or dual x-ray absorptiometry (DXA). Exclusion criteria included studies enrolling male BC patients that did not stratify results by gender; the inclusion of other types of cancer; if chemotherapy was not administered; or if body composition was assessed by means other than CT or DXA (e.g., BMI or body surface area). Reviews, case studies, and abstracts were also excluded.

Eight article met the inclusion criteria. The results of all studies were based on chart review data, and four of the articles were part of larger, prospective studies. Eligibility criteria differed across the clinical trials, e.g., some studies excluded patients with preexisting laboratory abnormalities or with low performance scores. In addition to the heterogeneity among the trials, quality varied as no study described the representativeness of the study sample to the general population and the majority of the studies (5/8) did not provide demographic data other than age.

While all stages of BC were reflected in the systematic review, treatment courses varied and included anthracyclines alone or with cyclophosphamide, taxanes, 5-fluorouracil, capecitabine, trastuzumab, and bevacizumab.

Most studies (7/8) used the National Cancer Institute’s Common Terminology Criteria for Adverse Events to measure chemotoxicity.

Definitions of low LBM differed across the studies. Four studies estimated total LBM, and two studies calculated skeletal muscle area (SMA). Further, five studies calculated the skeletal muscle index (SMI), which was the SMA divided by the patient’s height in meters. Other parameters included the skeletal muscle density (SMD) and the muscle quality, which was determined by multiplying SMI times SMD, yielding the skeletal muscle gauge variable, and adipose radiodensity.

Only three studies evaluated the association between adipose tissue (AT) and chemotoxicity, and measurements differed from subcutaneous AT, visceral AT (VAT), to total abdominal AT volume and ratio.

Among the studies examining LBM and chemotoxicity, five analyzed the incidence of laboratory-based hematologic or hepatobiliary toxicity or patient-reported toxicity. Two other studies examined the incidence of low LBM among patients who experienced toxicity.

Investigators found that there was an inverse association between LBM and toxicity in seven out of eight studies. The risk of grade >3 toxicity of any type increased 36% for every 5-kg decrease in LBM. Three studies examined the association between AT and chemotoxicity and were inconclusive. One study found that a higher VAT volume and a higher VAT to total abdominal fat volume ratio were associated with a greater incidence of grade 4 leukopenia independent of being over- or underweight. Obesity was not associated with grade 4 hematologic toxicity. There was a significant positive correlation between doxorubicin area under the curve (AUC) and VAT volume and AUC with total abdominal fat; however, another study found no association between measures of adiposity and severe hematologic, hepatobiliary, gastrointestinal, or neurologic toxicity during chemotherapy for BC.

While more studies are needed in this area, pharmacists managing the care of women with BC should be particularly cognizant of the risk that low LBM may play in the development of both hematologic and nonhematologic chemotherapy-induced toxicity and the need to closely monitor this patient population.

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