Chemotherapy-Related Toxic Effects and Quality of Life and Physical Functioning in Older Patients

Abstract

Importance: Although older patients are at increased risk of developing grade 3 or higher chemotherapy-related toxic effects, no studies, to our knowledge, have focused on the association between toxic effects and quality of life (QOL) and physical functioning.

Objective: To investigate the association between grade 3 or higher chemotherapy-related toxic effects and QOL and physical functioning over time in older patients.

Design, setting, and participants: In this prospective, multicenter cohort study, patients aged 70 years or older who were scheduled to receive chemotherapy with curative or palliative intent and a geriatric assessment were included. Patients were treated with chemotherapy between December 2015 and December 2021. Quality of life and physical functioning were analyzed at baseline and after 6 months and 12 months.

Exposures: Common Terminology Criteria for Adverse Events grade 3 or higher chemotherapy-related toxic effects.

Main outcomes and measures: The main outcome was a composite end point, defined as a decline in QOL and/or physical functioning or mortality at 6 months and 12 months after chemotherapy initiation. Associations between toxic effects and the composite end point were analyzed with multivariable logistic regression models.

Results: Of the 276 patients, the median age was 74 years (IQR, 72-77 years), 177 (64%) were male, 196 (71%) received chemotherapy with curative intent, and 157 (57%) had gastrointestinal cancers. Among the total patients, 145 (53%) had deficits in 2 or more of the 4 domains of the geriatric assessment and were classified as frail. Grade 3 or higher toxic effects were observed in 94 patients (65%) with frailty and 66 (50%) of those without frailty (P = .01). Decline in QOL and/or physical functioning or death was observed in 76% of patients with frailty and in 64% to 68% of those without frailty. Among patients with frailty, grade 3 or higher toxic effects were associated with the composite end point at 6 months (odds ratio [OR], 2.62; 95% CI, 1.14-6.05) but not at 12 months (OR, 1.09; 95% CI, 0.45-2.64) and were associated with mortality at 12 months (OR, 3.54; 95% CI, 1.50-8.33). Toxic effects were not associated with the composite end point in patients without frailty (6 months: OR, 0.76; 95% CI, 0.36-1.64; 12 months: OR, 1.06; 95% CI, 0.46-2.43).

Conclusions and relevance: In this prospective cohort study of 276 patients aged 70 or older who were treated with chemotherapy, patients with frailty had more grade 3 or higher toxic effects than those without frailty, and the occurrence of toxic effects was associated with a decline in QOL and/or physical functioning or mortality after 1 year. Toxic effects were not associated with poor outcomes in patients without frailty. Pretreatment frailty screening and individualized treatment adaptions could prevent a treatment-related decline of remaining health.

Figure 1.. Incidence of Various Treatment Outcomes in All Patients by Frailty Status

Frequencies of grades 3 to 5 toxic effects (P = .01), nonhematologic toxic effects (P = .03), dose reduction during treatment (P = .04), early treatment discontinuation (P = .009), and hospitalization (P = .003) were significantly different between patients with and without frailty, analyzed with a χ² test. ^aP < .05. ^bThe worst grade of toxic effects was documented (grade e3). Of the patients who developed grades 3 to 5 toxic effects, 91% developed their first toxic effects within the first 2 months after chemotherapy initiation, and 9% developed their first toxic effects after 2 months. ^cAmong patients with frailty, reasons for early treatment discontinuation were toxic effects (64%), tumor progression (29%), death to other cause (3%), clinical deterioration (3%), or other reasons (1%). Among patients without frailty, reasons for early treatment discontinuation were toxic effects (56%), tumor progression (28%), or clinical deterioration (16%).

Figure 2.. Composite End Points After 6 Months and 12 Months by Frailty Status and by the Absolute Number of Impaired Frailty Domains

A, Among living patients with frailty at 6 months, 40% still received chemotherapy, and 60% either completed or discontinued treatment. Among living patients with frailty at 12 months, 17% still received chemotherapy, and 83% either completed or discontinued treatment. B, Among living patients without frailty at 6 months, 30% still received chemotherapy, and 70% either completed or discontinued chemotherapy. Among living patients without frailty at 12 months, 9% still received chemotherapy, and 91% completed or discontinued treatment. C and D, Frailty domains include somatic, functional, psychological, and social. Decline represents either a decline in quality of life (QOL) or a decline in physical functioning (PF). No follow-up consists of living patients without a completed follow-up questionnaire at the specified time point.

Figure 3.. Composite End Points of Patients After 6 Months and 12 Months by Grade 3 or Higher Chemotherapy-Related Toxic Effects Status

No follow-up consists of living patients without a completed follow-up questionnaire at the specified time point. PF indicates physical functioning; QOL, quality of life. ^aP < .05, derived from the multivariable logistic regression models shown in Table 2.