Rupal Ramani

Predicting Chemotherapy Toxicity in Older Adults With Cancer: A Prospective Multicenter Study

PURPOSE Older adults are vulnerable to chemotherapy toxicity; however, there are limited data to identify those at risk. The goals of this study are to identify risk factors for chemotherapy toxicity in older adults and develop a risk stratification schema for chemotherapy toxicity. PATIENTS AND METHODS Patients age ≥ 65 years with cancer from seven institutions completed a prechemotherapy assessment that captured sociodemographics, tumor/treatment variables, laboratory test results, and geriatric assessment variables (function, comorbidity, cognition, psychological state, social activity/support, and nutritional status). Patients were followed through the chemotherapy course to capture grade 3 (severe), grade 4 (life-threatening or disabling), and grade 5 (death) as defined by the National Cancer Institute Common Terminology Criteria for Adverse Events. RESULTS In total, 500 patients with a mean age of 73 years (range, 65 to 91 years) with stage I to IV lung (29%), GI (27%), gynecologic (17%), breast (11%), genitourinary (10%), or other (6%) cancer joined this prospective study. Grade 3 to 5 toxicity occurred in 53% of the patients (39% grade 3, 12% grade 4, 2% grade 5). A predictive model for grade 3 to 5 toxicity was developed that consisted of geriatric assessment variables, laboratory test values, and patient, tumor, and treatment characteristics. A scoring system in which the median risk score was 7 (range, 0 to 19) and risk stratification schema (risk score: percent incidence of grade 3 to 5 toxicity) identified older adults at low (0 to 5 points; 30%), intermediate (6 to 9 points; 52%), or high risk (10 to 19 points; 83%) of chemotherapy toxicity (P < .001). CONCLUSION A risk stratification schema can establish the risk of chemotherapy toxicity in older adults. Geriatric assessment variables independently predicted the risk of toxicity.

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.

Factors associated with high burden in caregivers of older adults with cancer.

Older adults with cancer are vulnerable to functional decline, which places greater onus on caregivers. Few studies have prospectively examined burden in caregivers of older cancer patients. The objective of this study was to determine the factors associated with high caregiver burden.

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.

The Effect of Aromatase Inhibition on the Cognitive Function of Older Patients With Breast Cancer

INTRODUCTION This study evaluated the association between aromatase inhibitor (AI) therapy and cognitive function (over a 6-month period) in a cohort of patients aged ≥ 60 years compared with an age-matched healthy control group, and it evaluated changes in regional cerebral metabolism as measured by positron emission tomography (PET) scans of the brain done in a subset of the patient cohort. PATIENTS AND METHODS Thirty-five patients (32 evaluable) and 35 healthy controls were recruited to this study. Patients with breast cancer completed a neuropsychological battery, self-reported memory questionnaire, and geriatric assessment before initiation of AI therapy and again 6 months later. Age-matched healthy control participants completed the same assessments at the same time points as the patient group. RESULTS No significant decline in cognitive function was seen among individuals receiving an AI from pretreatment to 6 months later compared with healthy controls. In the PET cohort over the same period, both standardized volume of interest and statistical parametric mapping analyses detected specific changes in metabolic activity between baseline and follow-up uniquely in the AI patients, most significantly in the medial temporal lobes. CONCLUSION Although patients undergoing AI treatment had few changes in neuropsychological performance compared with healthy controls over a 6-month period, regionally specific changes in cerebral metabolic activity were identified during this interval in the patient group. Additional longitudinal follow-up is needed to understand the potential clinical implications of these findings.

Use of Complementary Medications among Older Adults with Cancer

Little is known about complementary medication use among older adults with cancer, particularly those who are receiving chemotherapy. The objective of this study was to evaluate the prevalence of complementary medication use and to identify the factors associated with its use among older adults with cancer.

Age-Related Changes in Nanoparticle Albumin-Bound Paclitaxel Pharmacokinetics and Pharmacodynamics: Influence of Chronological Versus Functional Age

PURPOSE This study evaluated age-related changes in pharmacokinetic and pharmacodynamic parameters of nanoparticle albumin-bound paclitaxel (nab-paclitaxel) in patients with metastatic breast cancer. METHODS Forty patients received nab-paclitaxel (100 mg/m(2) weekly for 3 weeks followed by a 1-week break) as first- or second-line chemotherapy. Blood samples were collected for analysis, and response was assessed every two cycles. Planned statistical analyses included linear regression to examine the relationship between age and pharmacokinetic variables (ln clearance [CL] and ln area under the curve [AUC]) and two-sided two-sample t tests to evaluate age differences in pharmacodynamic variables. The association between chemotherapy toxicity risk scores and pharmacokinetic and pharmacodynamic variables including grade ≥ 3 toxicity were examined post hoc. RESULTS Of 40 patients enrolled, 39 (98%) were evaluable (mean age: 60 years; range: 30-81 years). A partial response was achieved in 31%, and 38% had stable disease. There was a borderline positive association between age and 24-hour ln AUC (slope = 0.011; SE = 0.006; p = .055). Grade 3 toxicity was experienced by 26% (8% hematologic, 18% nonhematologic). There were no differences in age based on the presence of grade 3 toxicity (p = .75), dose reductions (p = .38), or dose omissions (p = .15). A significant association was noted between chemotherapy toxicity risk score category and presence of grade 3 toxicity (toxicity rate by risk score category: low, 5 of 30 patients; medium, 3 of 6 patients; high, 2 of 3 patients; p = .041). CONCLUSION A borderline significant relationship exists between age and 24-hour AUC, but no differences were noted for pharmacodynamic variables (grade 3 toxicity, dose reductions, or dose omissions) based on age. There is an association between toxicity risk score and grade ≥ 3 chemotherapy toxicity and pharmacokinetic variables. The treatment is well tolerated across all age groups.

Are Disagreements in Caregiver and Patient Assessment of Patient Health Associated with Increased Caregiver Burden in Caregivers of Older Adults with Cancer

Cancer‐related therapy is increasingly administered in the outpatient setting, resulting in increased dependence on caregivers suggest to provide physical and emotional support to patients. This article describes differences in patient versus caregiver assessments of patient health, considering caregiver perceptions of the patients health and abilities compared to that reported by the patient.

P5-19-05: Age-Related Changes in the Pharmacokinetics (pK), Response, and Toxicity of Weekly nab-Paclitaxel in Patients with Metastatic Breast Cancer (MBC).

Background: Although cancer is a disease of aging, few studies have evaluated the association between patient age and the pK or pharmacodynamics (pD) of cancer therapeutics. The goals of this study were 1) to evaluate the age-related changes in the pK and pD of weekly nab -paclitaxel in patients with MBC; 2) to determine response rate; and 3) to explore the relationship of age with pK and pD parameters (i.e., dose reductions, dose delays and grade ≥ 3 toxicities). Patients and Methods: Forty patients with MBC, receiving 1 st or 2 nd line chemotherapy, entered an IRB approved protocol to evaluate the age-related changes in the pK of weekly nab -paclitaxel administered at 100 mg/m 2 IV for 3 weeks followed by a 1-week break. Patients were accrued from 4 age strata 70 years of age. Blood samples were collected for pK analysis with the first dose of nab -paclitaxel. Response was assessed every 2 cycles. Toxicity was graded using the NCI Common Toxicity Criteria for Adverse Events (v 3.0) and was adjudicated as attributable to nab -paclitaxel if it was possibly, probably, or definitely related. Linear regression analysis was used to examine the strength of the relationship between patient age and natural logarithm of 24 hour area under the curve (AUC). Two-sided two-sample t-tests were used to assess if there was a difference in mean age based on the presence of pD variables (i.e., dose reductions, dose delays and grade ≥ 3 toxicities). The significance level was set to 0.05. Results: Of the 40 patients who entered the study, 39 (98%) were evaluable with a mean age of 60 (SD=13.4; min=30; max=81). Patients were accrued in the following age cohorts: 70 (n= 9; 23%) years of age. The median number of courses completed was 4 (min=1, max=21). The response rate was: 0% (n=0) CR, 31% (n=12) PR, 38% (n=15) SD. Grade 3 toxicity was experienced by 26% (n=10). We observed 8% (n=3) grade 3 hematological toxicities [neutrophils (n=1; 3%), leukocytes (n=2; 5%)] and 18% (n=7) grade 3 non-hematological toxicities [nausea and hypophosphatemia (n=1; 3%), diarrhea and infection without neutropenia (n=1; 3%), fatigue (n=2; 5%), hyponatremia (n=1; 3%), and infections without neutropenia (n=2; 5%)]. There were no cases of grade 4 or 5 toxicity. Grade 2 sensory neuropathy was experienced by 8% (n=3; no cases in the 70+ age cohort). Dose reductions or course delays were experienced by 62% (n=24) and 21% (n=8), respectively. There was a borderline significant positive association between age and natural logarithm of total nab -paclitaxel 24 hour AUC (coef=.01; se=.006; p=0.055; n=36). There were no differences in the mean ages based on the presence of grade 3 or higher toxicity (p =0.75), need for dose reductions (p=0.48), or need for dose delays (p=0.61). Discussion: There is a borderline statistically significant relationship between age and 24 hour AUC but no differences in mean age based on pD variables (i.e., dose reductions, dose delays and grade ≥ 3 toxicities) were identified. The treatment is well-tolerated across all age groups. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P5-19-05.