Geriatric assessment is associated with completion of chemotherapy, toxicity, and survival in older adults with cancer

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Abstract

Objectives

Our purpose was to determine whether geriatric assessments are associated with completion of a chemotherapy course, grade III/IV toxicity or survival in older adults with cancer.

Materials and Methods

In this prospective cohort study, patients aged 65 years and older with colorectal, lung, or breast cancer or lymphoma completed a brief geriatric assessment prior to chemotherapy. Endpoints included completion of the planned number of chemotherapy cycles, grade III/IV toxicity and survival. Multivariate logistic regression determined which factors were independently associated with completion of therapy, grade III/IV toxicity or death.

Results

Sixty-five patients were enrolled in the study. The median age was 73 years (range 65–89). Geriatric syndromes were common, including depression (21.5%), dependence on others to carry out instrumental activities of daily living (38.5%) and activities of daily living (10.8%), and comorbidities (mild 47.7%, moderate 20%, severe 15.4%). Of the 65 participants, 67.6% completed the planned number of chemotherapy cycles. Curative intent therapy [OR 4.97 (95% CI 1.21–18.81)], Eastern Cooperative Oncology Group (ECOG) performance status 2–3 [OR 0.089 (0.015–0.53)] and renal function [OR 1.03 (1.00–1.06) per ml/min] were significantly associated with therapy completion. Furthermore, 31.1% experienced grade III/IV non-hematologic toxicity. Moderate to severe comorbidities significantly increased the risk of grade III/IV non-hematologic toxicity [OR 6.13 (1.65–22.74)]. Patients who received chemotherapy with curative intent had lower mortality [HR 0.15 (0.06–0.42)], while patients who reported a fall in the month prior to chemotherapy had an increased risk of death [HR 3.20 (1.13–9.11)].

Conclusions

Geriatric assessment is associated with completion of a planned number of cycles of chemotherapy, grade III/IV non-hematologic toxicity, and mortality.

Introduction

The incidence of most cancers increases with age. With the aging of the population, a 67% increase in cancer incidence in older adults in the United States is expected by the year 2030.1 Numerous studies have shown that older adults are undertreated.[2], [3], [4] This may be, in part, due to concerns about a greater risk of treatment toxicity in older adults. Decision-making regarding older adults is also challenging due to the underrepresentation of older adults in clinical trials, and the frequent occurrence of comorbidities, functional limitations or other geriatric syndromes, which may influence a clinician's estimate of the risk of therapy and their decision to recommend chemotherapy.5 Unfortunately, standard oncology assessments do not routinely assess certain geriatric parameters, including depression, cognition, functional decline, falls, and polypharmacy.

Two recent prospective cohort studies have demonstrated the utility of a geriatric assessment in older adults with cancer in predicting tolerance of chemotherapy.[6], [7] In the Cancer and Aging Research Group (CARG) study, geriatric assessment parameters including hearing impairment, falls, requiring assistance with medications, decreased ability to walk one block and decreased social activity were associated with an increased risk of grade III or greater toxicity with chemotherapy.8 In the study by Extermann et al., geriatric parameters were also predictive of chemotherapy toxicity. Instrumental activities of daily living predicted grade III or greater hematologic toxicity, while poor performance status, impaired cognition and nutritional impairment predicted grade III or greater non-hematologic toxicity.7

Completion of chemotherapy is also an important consideration in counseling older adults regarding the use of chemotherapy. In both the curative- and palliative-intent settings, estimating the benefit of chemotherapy is predicated on the patient completing the planned course of chemotherapy. Failure to complete a course of chemotherapy may be associated with poorer outcomes. Regarding patients with colorectal cancer, completion of adjuvant chemotherapy is associated with lower cancer-related mortality.9 Given that some patients will discontinue therapy, even in the absence of grade III/IV toxicity, determining which patients are less likely to complete a planned course of therapy will assist patients and clinicians in making decisions regarding chemotherapy and allow subsequent intervention to improve rates of completion of therapy among older adults with cancer. Finally, geriatric assessment is predictive of early mortality in older patients with cancer10; thus, ascertaining which older adults are at increased risk for mortality will further aid the decision-making process.

In this study, we sought to examine which geriatric assessment parameters were associated with completion of a planned course of chemotherapy, grade III/IV hematologic and non-hematologic toxicity of chemotherapy, and survival.

Section snippets

Methods

The Washington University School of Medicine Human Studies Committee approved this prospective study. Informed consent was obtained from patients age 65 or older with a biopsy-proven malignancy of the lung, breast, colon/rectum or lymphoma, who were likely to begin a course of chemotherapy. Patients receiving concurrent radiation therapy were excluded. Potential study candidates were identified from the patients who were seeking initial consultation or continued treatment with a medical

Results

From July 2008 to February 2012, 65 patients were enrolled. Baseline demographic and laboratory values are presented in Table 1. Geriatric syndromes were common, as shown in Table 2. Several chemotherapeutic and immunochemotherapeutic regimens were represented for each disease site. Regimens included FOLFOX with or without cetuximab (N = 18), capecitabine and oxaliplatin (N = 3), capecitabine alone (N = 3), docetaxel and cyclophosphamide with or without trastuzumab (N = 5), doxorubicin and

Discussion

Our study adds to the growing body of literature supporting the importance of geriatric assessment in older adults with cancer. In this small prospective cohort study, geriatric assessment parameters were associated with completion of a planned course of chemotherapy, grade III/IV non-hematologic toxicity, and mortality.

The primary outcome in our study was completion of a planned course of chemotherapy. This outcome differs subtly from studies assessing grade III/IV toxicity of chemotherapy. In

Disclosures and Conflict of Interest Statements

The authors have no conflicts of interest to disclose.

Author Contributions

Study concepts: Tanya M. Wildes, Alexander P. Ruwe, Ken Carson, Jay F. Piccirillo, Benjamin Tan, Graham Colditz

Study design: Tanya M. Wildes, Jay F. Piccirillo, Benjamin Tan

Data acquisition: Tanya M. Wildes, Alexander P. Ruwe, Chloe Fournier, Benjamin Tan

Quality control of data and algorithms: Tanya M. Wildes, Alexander P. Ruwe, Chloe Fournier, Benjamin Tan

Data analysis and interpretation: Tanya M. Wildes, Alexander P. Ruwe, Feng Gao, Ken Carson, Jay F. Piccirillo, Benjamin Tan, Graham Colditz

Acknowledgements

This publication was made possible by Grant Number KM1CA156708-01 through the National Cancer Institute (NCI) at the National Institutes of Health (NIH) and Grant Numbers UL1 TR000448, KL2 TR000450, TL1 TR000449 through The Clinical and Translational Science Award (CTSA) program of the National Center for Advancing Translational Sciences (NCATS) at the National Institutes of Health. Its contents are solely the responsibility of the authors and do not necessarily represent the official view of

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