Predictors of chemotherapy dose reduction at first cycle in patients age 65years and older with solid tumors

Gajra, Ajeet; Klepin, Heidi D.; Feng, Tao; Tew, William P.; Mohile, Supriya G.; Owusu, Cynthia; Gross, Cary P.; Lichtman, Stuart M.; Wildes, Tanya M.; Chapman, Andrew E.; Dotan, Efrat; Katheria, Vani; Zavala, Laura; Akiba, Chie; Hurria, Arti

doi:10.1016/j.jgo.2014.12.002

Cited by 48 publications

(56 citation statements)

References 27 publications

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“…Age-based primary dose reduction is not routinely recommended, but older age is independently associated with primary dose reduction in patients with solid tumours. 18 However, a reduction in toxicity, hospitalisation or discontinuation of therapy was not found in this study in relation to age.…”

Section: Discussioncontrasting

confidence: 63%

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study

et al. 2016

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BackgroundElderly patients with primary colorectal cancer (CRC) are less frequently treated with adjuvant chemotherapy than younger patients due to concerns regarding toxicity and efficiency. We investigated how age, performance status (PS) and comorbidity influence treatment outcomes.Patients and methodsA retrospective single-centre study of 529 patients with stages II–III CRC treated with adjuvant chemotherapy (5-fluorouracil/capecitabine+/÷oxaliplatin) from 2001 to 2011 at Herlev Hospital, Denmark. Baseline characteristics, chemotherapy and outcome were analysed with respect to age after adjusting for PS and comorbidity.ResultsElderly patients (>70 years) had significantly more comorbidity (p<0.001) and poorer PS (p=0.001) than younger patients. Elderly were more frequently treated with single-agent therapy (p=0.001) and at lower initial dose (p<0.001). There was no age-dependent difference in 3-year disease-free survival (DFS; HR 1.09, 95% CI 0.80 to 1.47, p=0.59), in grade 3–5 toxicity (29% vs 28%, p=0.86) or in 10-year CRC mortality (28%, HR 1.07, p=0.71). In elderly patients, a reduction in chemotherapy dose intensity compared with full dose had no impact on DFS or CRC mortality. Elderly patients receiving <50% of planned cycles had shorter DFS (HR=1.78, p=0.020) and higher CRC mortality (HR=2.17, p=0.027) than elderly receiving all cycles. Poor PS in younger and elderly patients was related to shorter DFS (HR=1.95, p=0.002; HR=1.6, p=0.035, respectively) and overall survival (OS; HR=2.28, p<0.001; HR=2.03, p=0.002). Comorbidity in younger patients was significantly related to shorter DFS (HR 2.72, p<0.001), OS (HR 3.16, p<0.001) and higher CRC mortality (HR 2.70, p=0.001).ConclusionsChoice of regimen, primary dose reduction and given dose intensity in patients treated with adjuvant chemotherapy for CRC were highly dependent on age. However, age had no impact on DFS and CRC mortality. Comorbidity in younger patients and PS in all patients were associated with shorter DFS and higher CRC mortality.

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Section: Discussioncontrasting

confidence: 63%

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study

et al. 2016

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“…Furthermore, we did not have data regarding whether patients had their first cycle chemotherapy doses adjusted based on RF (i.e., a primary dose reduction). However, very few patients (N=14) who had a primary dose reduction reported kidney or liver disease as a comorbidity and there were no significant differences in toxicity rates between patients who had a primary dose reduction and those who did not [37]. Only 4% of the population was over the age of 85, only 2% had BMI<18, and only 4% had a BMI >35.…”

Section: Discussionmentioning

confidence: 99%

Association between renal function and chemotherapy-related toxicity in older adults with cancer

Peterson

Hurria

Feng

et al. 2017

Journal of Geriatric Oncology

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Purpose To evaluate the association between renal function (RF) and chemotherapy-related toxicity (CRT) in older adults with cancer and to compare the effect of different RF formulas and body weight measurements on this association. Methods This is a secondary analysis of data from a prospective multicenter study of patients ≥ age 65 who were starting a new chemotherapy regimen. RF was estimated with 4 formulas (modified Jelliffe [Jelliffe], Cockcroft-Gault [CG], Wright, and Modification of Diet in Renal Disease [MDRD]), using actual, ideal and adjusted body weights for 492 patients. The association between baseline RF and grade 3–5 CRT was evaluated by unconditional logistic regression. Results As a continuous variable, decreased creatinine clearance (CrCl) calculated by CG with actual body weight was associated with increased odds of CRT (OR 1.12, P<0.01; 95% CI 1.04–1.20) indicating that on average for every 10 mL/min decrease in CrCl the odds of CRT increased by 12%. Very low RF (in the lowest 10%) with all formulas (CG, Jelliffe, Wright and MDRD) was associated with increased odds for CRT. This association is independent of the type of chemotherapy received (those requiring dose adjustment for renal function vs not). Neither primary dose reduction nor chemotherapy duration was associated with CRT. Serum creatinine alone was not associated with increased odds of CRT (OR 0.67, P=0.15). Conclusions Decreased RF is associated with increased odds of CRT and should be considered when assessing risk of CRT in older adults with cancer. Serum creatinine alone is not adequate for risk assessment.

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“…35, 36, 55 However, polypharmacy was not consistently included as part of the GA, which may be due to studies showing mixed results in the correlation between polypharmacy and various clinical outcomes, compared to strong correlations noted in other GA domains such as comorbidities, functional and nutritional status. 33, 56-59 For studies that did include medication assessment, the data was often analyzed and presented as number of medications. For example, Joly at al.…”

Section: Introductionmentioning

confidence: 99%

Polypharmacy and potentially inappropriate medication use in geriatric oncology

Sharma

Loh

Nightingale

et al. 2016

Journal of Geriatric Oncology

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107

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Polypharmacy is a highly prevalent problem in older persons, and is challenging to assess and improve due to variations in definitions of the problem and the heterogeneous methods of medication review and reduction. The purpose of this review is to summarize evidence regarding the prevalence and impact of polypharmacy in geriatric oncology patients and to provide recommendations for assessment and management. Polypharmacy has somewhat variably been incorporated into geriatric assessment studies in geriatric oncology, and polypharmacy has not been consistently evaluated as a predictor of negative outcomes in patients with cancer. Once screened, interventions for polypharmacy are even more uncertain. There is a great need to create standardized interventions to improve polypharmacy in geriatrics, and particularly in geriatric oncology. The process of deprescribing is aimed at reducing medications for which real or potential harm outweighs benefit, and there are numerous methods to determine which medications are candidates for deprescribing. However, deprescribing approaches have not been evaluated in older patients with cancer. Ultimately, methods to identify polypharmacy will need to be clearly defined and validated, and interventions to improve medication use will need to be based on clearly defined and standardized methods.

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Predictors of chemotherapy dose reduction at first cycle in patients age 65years and older with solid tumors

Cited by 48 publications

References 27 publications

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study

Efficacy and toxicity of adjuvant chemotherapy in elderly patients with colorectal cancer: the ACCORE study

Association between renal function and chemotherapy-related toxicity in older adults with cancer

Polypharmacy and potentially inappropriate medication use in geriatric oncology

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