Laura Zavala

Validation of a Prediction Tool for Chemotherapy Toxicity in Older Adults With Cancer

PURPOSE Older adults are at increased risk for chemotherapy toxicity, and standard oncology assessment measures cannot identify those at risk. A predictive model for chemotherapy toxicity was developed (N = 500) that consisted of geriatric assessment questions and other clinical variables. This study aims to externally validate this model in an independent cohort (N = 250). PATIENTS AND METHODS Patients age ≥ 65 years with a solid tumor, fluent in English, and who were scheduled to receive a new chemotherapy regimen were recruited from eight institutions. Risk of chemotherapy toxicity was calculated (low, medium, or high risk) on the basis of the prediction model before the start of chemotherapy. Chemotherapy-related toxicity was captured (grade 3 [hospitalization indicated], grade 4 [life threatening], and grade 5 [treatment-related death]). Validation of the prediction model was performed by calculating the area under the receiver-operating characteristic curve. RESULTS The study sample (N = 250) had a mean age of 73 years (range, 65 to 94 [standard deviation, 5.8]). More than one half of patients (58%) experienced grade ≥ 3 toxicity. Risk of toxicity increased with increasing risk score (36.7% low, 62.4% medium, 70.2% high risk; P < .001). The area under the curve of the receiver-operating characteristic curve was 0.65 (95% CI, 0.58 to 0.71), which was not statistically different from the development cohort (0.72; 95% CI, 0.68 to 0.77; P = .09). There was no association between Karnofsky Performance Status and chemotherapy toxicity (P = .25). CONCLUSION This study externally validated a chemotherapy toxicity predictive model for older adults with cancer. This predictive model should be considered when discussing the risks and benefits of chemotherapy with older adults.

Polypharmacy and Potentially Inappropriate Medication Use in Older Adults with Cancer Undergoing Chemotherapy: Effect on Chemotherapy‐Related Toxicity and Hospitalization During Treatment

To evaluate the prevalence of polypharmacy and potentially inappropriate medication (PIM) use and the association between these and chemotherapy‐related adverse events in older adults with cancer undergoing chemotherapy.

The relationship between age, anxiety, and depression in older adults with cancer.

In older men with prostate cancer, aging is associated with reduced anxiety and increased depression. The purpose of this study was to examine the association among age, anxiety, and depression in a cohort of older adults receiving chemotherapy.

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

PURPOSE Age-based reduction of chemotherapy dose with the first cycle (primary dose reduction, PDR) is not routinely guideline recommended. Few studies, however, have evaluated how frequently PDR is utilized in the treatment of older patients with cancer and which factors may be associated with this decision. METHODS We conducted a secondary analysis of a multi-institutional prospective cohort study of patients age ≥65 years treated with chemotherapy. The dose and regimen were at the discretion of the treating oncologist. The prevalence of PDR and its association with treatment intent (palliative vs. curative), tumor type, patient characteristics (sociodemographics and geriatric assessment variables), and chemotherapy-associated toxicity were evaluated. RESULTS Among 500 patients (mean age 73, range 65-91 years), 179 patients received curative intent chemotherapy and 321 patients received palliative intent chemotherapy, with PDR being more common in the latter sub-group (15% vs. 25%, p = 0.005). Increasing age was independently associated with PDR in both sub-groups. Comorbidity (prior cancer or liver/kidney disease) was independently associated with PDR in the palliative sub-group alone while Karnofsky Performance Status (KPS) was not associated with PDR in either subgroup. There was no significant difference in the rates of grades 3-5 toxicity, dose reductions, or delays with PDR. Patients in the palliative sub-group treated with PDR had higher rates of hospitalization compared to those treated with standard doses. CONCLUSION PDR is more common in the palliative setting, but is also utilized among patients treated with curative intent. Factors associated with PDR include age and comorbid conditions, but not KPS.

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

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 10mL/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.

Association of Pre‐Chemotherapy Peripheral Blood Pro‐Inflammatory and Coagulation Factors with Physical Function in Women with Breast Cancer

Breast cancer is a disease associated with aging. Before initiation of chemotherapy, an assessment of functional reserve is needed; however, simple performance assessment scores may not reflect the diverse nature of physical function and risk of toxicity among older adults. The focus of this article is on understanding the association between pre‐chemotherapy biomarkers (IL‐6, CRP, and D‐dimer) and measures of physical function.

Abstract P6-01-07: Association of baseline pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with baseline functional status in women with breast cancer (BC) undergoing chemotherapy

Background: Pro-inflammatory and coagulation factors such as IL-6, CRP and D-dimer serve as biomarkers for aging. The utility of these markers as biologic correlates of physical function in patients with BC is not known. This study was performed to determine if baseline serum markers of inflammation (IL-6, CRP) and coagulation (D-dimer) correlate with baseline functional status in women with stage I-III BC requiring chemotherapy (chemo). Methods: This is a prospective longitudinal study that enrolled 153 women across all age groups with BC who had pre-chemotherapy peripheral blood captured for IL-6, CRP, and D-dimer and a baseline assessment of the following functional status measures: activities of daily living (Medical Outcomes Study [MOS] Physical Health); instrumental activities of daily living (IADL); self-rated Karnofsky performance status (KPS); physician-rated KPS; number of falls in last 6 months; and Timed Up and Go (TUG). Peripheral blood samples were collected for measurement of IL-6, CRP and D-dimer. Quantitative IL-6 and CRP levels were obtained using NOVEX® immunoassay (Invitrogen) and D-dimer levels were measured with Nanopia®D-dimer(Sekisui). Univariate analyses were performed to describe correlations of these three biomarkers and 6 measures of physical function. Results: 153 patients (mean age of 57.5 y, range 30-81 y) with stage I- III BC (Stages I [n=35; 23%], II [n=82; 54%], III [n=36; 24%]) were enrolled. Chemo regimens include: doxorubicin+cyclophosphamide/ paclitaxel(AC-T: 44%), docetaxel/cyclophosphamide (TC: 35%), docetaxel/carboplatin/trastuzumab (TCH: 7%) and other regimen(14%). Scores for the physical function measures are as follow: MOS (median 89, range 0-100); IADL (median 14, range 4-14); self-rated KPS (median 90, range 60-100); physician-rated KPS (median 100, range 80-100); TUG (median 9 seconds, range 5-18). Serum biomarkers measurements and distributions are listed in table 1. There were associations between decreased physical function by IADL and increased IL-6 (p Citation Format: Yuan Yuan, Nilesh Vora, Tao Feng, Joanne Mortimer, Thehang Luu, George Somlo, Joseph Chao, Vivi Tran, Shu Mi, Tim Synold, James Waisman, Laura Zavala, Vani Katheria, Arti Hurria. Association of baseline pro-inflammatory (IL-6, CRP) and coagulation (D-dimer) markers with baseline functional status in women with breast cancer (BC) undergoing chemotherapy [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-01-07.