ABSTRACT
BACKGROUND: In the field of exercise oncology, there is a need to quantify the potential benefits of moderate, self-directed physical activity during active treatment. In a pooled analysis of three identical single-arm intervention studies, we investigate the association of activity tracker steps with patient-reported toxicities during chemotherapy. METHODS: Women with early breast cancer who were enrolled in the intervention studies reported their symptom severity every 2-3 weeks throughout chemotherapy, and daily steps were documented through a Fitbit activity tracker. Relative risks (RR) and 95% confidence intervals (CI) were calculated using Poisson regression models with robust variance. For outcomes significant in unadjusted models, adjusted RRs were calculated controlling for race, age, and education level. Tracker step cut point (high step, low step) was determined by the means. Cumulative incidence functions of moderate, severe, and very severe (MSVS) symptoms were estimated using the Kaplan-Meier method and compared using a Cox proportional hazard model. RESULTS: In a sample of 283 women, mean age was 56 years and 76% were White. Mean tracker-documented steps/week were 29,625, with 55% walking below the mean (low step) and 45% above (high step). In multivariable analysis, high step patients had lower risk for fatigue [RR 0.83 (0.70, 0.99)] (p = 0.04), anxiety [RR 0.59 (0.42, 0.84)] (p = 0.003), nausea [RR 0.66 (0.46, 0.96)] (p = 0.03), depression [RR 0.59 (0.37, 0.03)] (p = 0.02), and ≥ 6 MSVS symptoms [RR 0.73 (0.54, 1.00)] (p = 0.05) and had 36% lower risk for dose reductions [RR 0.64 (95% CI 0.43, 0.97)] (p = 0.03). CONCLUSION: Self-directed walking at a rate of at least 30,000 steps/week may moderate the severity of treatment side effects during chemotherapy for early breast cancer. TRIAL NUMBERS: NCT02167932, NCT02328313, NCT03761706.
Subject(s)
Breast Neoplasms , Drug-Related Side Effects and Adverse Reactions , Female , Humans , Middle Aged , Anxiety , Breast Neoplasms/drug therapy , Exercise , WalkingABSTRACT
BACKGROUND: Cognitive difficulties have been described after chemotherapy for breast cancer, but there is no standard of care to improve cognitive outcomes in these patients. This trial examined the feasibility, tolerability, acceptability, and preliminary effects of memantine to prevent cognitive decline during chemotherapy for breast cancer. METHODS: Patients with stage I-III breast cancer, scheduled for neo/adjuvant chemotherapy, completed a cognitive battery prior to and 4 weeks after completing chemotherapy. Memantine (10 mg BID) was administered concurrent with chemotherapy. Our primary cognitive outcome was visual working memory assessed by the Delayed Matching to Sample test. We used the Brief Medication Questionnaire to assess acceptability. RESULTS: Of 126 patients approached, 56 (44%) enrolled. Forty-five (80%) received ≥1 dose of memantine and completed pre-post assessments. Seventy-six percent reported taking ≥90% of scheduled doses. Participants were mean age of 56, 77% White, and 57% had stage I disease. Sixty-four percent had stable or improved Delayed Matching to Sample test scores. Stable or improved cognition was observed in 87%-91% across objective cognitive domain composite measures. Sixty-six percent self-reported stable or improved cognitive symptoms. There were seven greater than or equal to grade 3 adverse events; two were possibly related to memantine. Only 5% reported that taking memantine was a disruption to their lives. CONCLUSIONS: Memantine was well-tolerated and consistently taken by a large majority of patients receiving breast cancer chemotherapy. The majority demonstrated stable or improved cognition from pre- to post-assessment. Randomized trials are needed to determine memantine's efficacy to ameliorate cognitive loss. TRIAL REGISTRATION: ClinicalTrials.gov NCT04033419.
Subject(s)
Breast Neoplasms , Cognitive Dysfunction , Humans , Middle Aged , Female , Memantine/adverse effects , Breast Neoplasms/drug therapy , Feasibility Studies , CognitionSubject(s)
Drug-Related Side Effects and Adverse Reactions/diagnosis , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Medication Adherence/statistics & numerical data , Protein Kinase Inhibitors/adverse effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Self-Management , Telemedicine/statistics & numerical data , Adult , Drug-Related Side Effects and Adverse Reactions/etiology , Follow-Up Studies , Humans , Patient Reported Outcome Measures , Pilot Projects , PrognosisABSTRACT
Adjuvant human epidermal growth factor receptor 2 (HER2)-directed treatment has changed dramatically over the past decade. Historically, the addition of 1 year of trastuzumab to adjuvant chemotherapy has significantly improved both disease-free survival and overall survival across several studies. More recently, and in the metastatic setting, dual HER2-targeted therapy-beyond that of trastuzumab alone, and in combination with monoclonal antibodies such as pertuzumab and tyrosine kinase inhibitors such as lapatinib-has shown a survival benefit. As is common in drug development, promising agents in the metastatic setting are then examined in the curative setting. This article will provide an overview of the efficacy of dual HER2-targeted therapy in the adjuvant setting as reported in the APHINITY, ExteNET, and ALTTO trials. Potential toxicities with dual HER2-targeted therapy and the financial consequences of adding additional HER2-targeted therapy, beyond trastuzumab, in the adjuvant setting will also be discussed.
