Chemotherapy Toxicity Correlates With Nutritional Factors in Solid Tumors

Efrat Dotan, MD

Efrat Dotan, MD

An association was found between a lower risk of grade 3 or higher chemotherapy toxicity with higher body mass indexes (BMIs) and normal albumin, a protein made in the liver, levels in older adult patients with solid tumors, according to an analysis of a prospective, multicenter study.

“Our study provides additional support for the important impact of the BMI and albumin level on the tolerance of chemotherapy. Oncologists should carefully consider these factors as part of a comprehensive [geriatric assessment] before recommended chemotherapy for older adults with cancer,” Efrat Dotan, MD, Fox Chase Cancer Center, et al, wrote in their study.

Overall, 750 patients with mostly stage IV disease were enrolled in the trial, and the median age was 72 years old (range, 65-94). The median BMI prior to treatment was 26 kg/m²(range, 15.1‐52.1 kg/m²), and the median albumin value was 3.9 mg/dL (range, 1.0‐5.0 mg/dL).

Grade 3 or greater chemotherapy toxicity was observed in 54.7% of patients, and univariate analysis showed patients with >10% unintentional weight loss (UWL) had a 52% increased risk of developing grade 3+ toxicity than patients with ≤5% UWL (odds ratio [OR], 1.52;P=.04). Multivariable analysis, however, demonstrated that this association was not sustained after adjustments for the Cancer and Aging Research Group (CARG) toxicity risk group, BMI, and albumin level at treatment initiation (adjusted OR [AOR], 0.87; P=.58).

An association was observed between a higher BMI at treatment initiation and a lower risk of grade 3+ chemotherapy toxicity. The risk of grade 3+ chemotherapy toxicity decreased as BMI level increased, but investigators noted that this negative association was marginally statistically significant in the multivariable analysis (univariateP=.009; multivariable P=.06).

Patients with BMIs ≥ 30 kg/m²had approximately 40% less risk of grade 3+ chemotherapy toxicity than those with 18.5 to 24.9 kg/m²(AOR, 0.65; P=.06). Additionally, patients with low albumin levels of ≤3.6 mg/dL had a higher risk of grade 3+ chemotherapy toxicity compared with those with normal albumin levels of >3.6 mg/dL (AOR, 1.50; P=.03).

Associations between UWL, BMI, and albumin levels with grade 3+ chemotherapy toxicity were further analyzed to include adjustments for analysis by stage (I-III versus IV), analysis restricted to patients with gastrointestinal (GI) or lung cancer, and other variables; these analyses led to similar results, investigators noted.

The protective effect of a high BMI of ≥30 kg/m²was noted for patients with low albumin levels (AOR, 0.43; P=.03). A decrease in the risk of grade 3+ chemotherapy toxicity was observed in patients with normal albumin levels, particularly among those with BMIs of 18.5 to 24.9 kg/m²compared with patients with a low albumin level (AOR, 0.50; P=.02). Investigators also observed the lowest risk of grade 3+ chemotherapy toxicity among patients with BMIs ≥ 30 kg/m²and normal albumin levels versus patients with BMIs of 18.5 to 24.9 kg/m²and low albumin levels (AOR, 0.41; P= .008).

The joint effect of BMI and albumin levels was evaluated in 2 subgroups of patients, including those with low and medium/high CARG toxicity risk groups. The lowest risk of grade 3+ chemotherapy toxicity were patients with BMIs ≥ 30 kg/m2 and normal albumin levels (AOR for low risk, 0.12;P=.007; AOR for medium/high risk, 0.49; P=.06).

This was a secondary analysis of a prospective longitudinal study, conducted at 10 institutions in the United States. Patients had to be starting a new chemotherapy regimen for any solid tumor malignancy to be included on the trial and be aged 65 or older. A geriatric assessment was conducted prior to the initiation of chemotherapy, which included measures of nutritional status, financial status, comorbidity, psychological state, social support, and cognition.

The primary objective of the study was to develop a prediction model of chemotherapy toxicity. The CARG score, composed of 11 variables including age, tumor type, and treatment variables, was developed and validated with the best subset method to identify the combination of variables that could best predict risk of chemotherapy toxicity.

The study demonstrated an increased risk of grade 3+ chemotherapy toxicity in patients aged 65 or older with low BMI and low albumin levels, a group of patients that is already associated with a higher prevalence of undernutrition. UWL is another clinical factor that is associated with poorer outcomes and has been suggested as a nutritional status assessment tool for patients with cancer.

Investigators concluded that further studies are needed to validate these results and to evaluate interventions that can improve the nutritional status of older patients with solid tumors who are undergoing therapy.

Reference:

Dotan E, Tew WP, Mohile SG, et al. Associations between nutritional factors and chemotherapy toxicity in older adults with solid tumors [Published Online March 0, 2020].Cancer. DOI:10.1002/cncr.32718.