Study design and methods for the pilot study of muscadine grape extract supplement to improve fatigue among older adult cancer survivors (FOCUS) trial.

INTRODUCTION: Fatigue is a prevalent symptom among both cancer survivors and older adults. Negative consequences of fatigue include increased sedentary behavior, decreased physical activity and function, and lower quality of life. Few pharmacologic interventions improve fatigue. Our preclinical and clinical data show promising effects of a muscadine grape extract supplement (MGES) on oxidative stress, mitochondrial bioenergetics, the microbiome, and the symptom of fatigue. This pilot study seeks to translate these observations to cancer survivorship by testing the preliminary effect of MGE supplementation on older adult cancer survivors with self-reported fatigue. MATERIALS AND METHODS: We designed a double-blinded placebo-controlled pilot study to evaluate preliminary efficacy of MGE supplementation versus placebo on fatigue among older adult cancer survivors (aged ≥65 years) who report baseline fatigue. Sixty-four participants will be enrolled and randomized 1:1 to twice daily MGES (four tablets twice daily) versus placebo for 12 weeks. The primary outcome is change in Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue score from baseline to 12 weeks. Secondary outcomes are change in self-reported physical function, physical fitness (6-min walk test), self-reported physical activity, global quality of life (QOL), and the Fried frailty index. Correlative biomarker assays will assess changes in 8-hydroxy-2 deoxyguanosine, peripheral blood mitochondrial function, inflammatory markers, and the gut microbiome. DISCUSSION: This pilot study builds on preclinical and clinical observations to estimate effects of MGE supplementation on fatigue, physical function, QOL, and biologic correlates in older adult cancer survivors. Trial registration #: CT.govNCT04495751; IND 152908.

Feasibility and Acceptability of a Multi-Modality Self-Management Intervention for Head and Neck Cancer Caregivers: A Pilot Randomized Trial.

BACKGROUND: Head and neck cancer (HNC) patients undergoing radiation therapy (RT) experience significant side effects, presenting challenging care tasks for their informal (unpaid) caregivers. HNC caregivers report low caregiving self-efficacy, high distress, and interest in supportive care interventions. OBJECTIVE: This randomized pilot trial assessed the feasibility and acceptability of a 6 to 7 week supported self-management intervention (Prepare to Care) offering psychoeducation and stress management skills building for caregivers of patients receiving RT for HNC. METHODS: Caregivers were randomized to Prepare to Care or standard of care. Primary feasibility measures included participation and retention percentages. Assessments were completed before the intervention, at intervention completion, and 6-weeks later after intervention completion. RESULTS: Caregivers (N = 38) were predominantly female (88.6%), an average age of 56 years old, and a spouse/partner to the patient (71.4%). Participation percent was 42.2%; retention at intervention conclusion was 80% and 77% at the 6-week follow-up. Quantitative and qualitative results support acceptability, with 64% to 88% reporting each intervention module was helpful (quite a bit or very). Intervention caregivers reported a significantly greater improvement in self-efficacy for progressive muscle relaxation (PMR). CONCLUSIONS: Prepare to Care and the randomized pilot trial methods are feasible and acceptable for HNC caregivers of patients receiving RT. A significant treatment effect was observed for self-efficacy for PMR, and findings were in the expected direction regarding improved caregiving self-efficacy. Further research is necessary to determine the efficacy of this intervention with a focus on increased engagement strategies and longer-term outcomes. TRIAL REGISTRATION: NCT03032250.

Phase I Study of Muscadine Grape Extract for Patients With Advanced Cancer.

OBJECTIVE: Preclinical studies with muscadine grape extract (MGE) show antitumor activity and decreased systemic inflammation. This phase I study (NCT02583269) assessed safety and tolerability of a proprietary MGE preparation in patients with advanced solid tumors. METHODS: Patients with metastatic or unresectable cancers who were progressing on standard therapies were assigned to MGE in a standard 3+3 design. Five dose levels were tested (320 to 1600 mg total phenolics/d). Safety and maximum-tolerated dose were assessed after 4 weeks. Patients were evaluated for response at 8 weeks and continued on MGE if clinically stable. Secondary outcomes were response, survival, adherence, fatigue, and quality of life (QOL). RESULTS: In total, 23 patients (lung, n=7; gastrointestinal, n=7; genitourinary, n=6; other, n=3) received MGE capsules by mouth twice daily. The cohort [median age 72 years, 48% Eastern Cooperative Oncology Group (ECOG) 2] was heavily pretreated. After 4 weeks on MGE, possibly attributable adverse events grade 2 or higher were fatigue (n=1), decreased lymphocyte count (n=1), and constipation (n=2), including 1 dose-limiting toxicity for grade 3 constipation. Maximum-tolerated dose was not reached. No partial responses were observed. Median time on therapy was 8 weeks, with 29% of patients treated beyond 16 weeks and a median overall survival of 7.2 months. QOL and fatigue levels were stable from baseline to 8 weeks. Higher MGE dose was correlated with improvement in self-reported physical well-being QOL at 8 weeks (r=0.6; P=0.04). CONCLUSIONS: MGE is safe and well-tolerated in heavily pretreated and older cancer patients.  The potential anticancer properties and the effects of MGE on physical well-being and QOL metrics will be evaluated in future studies.

Suboptimal uptake of human papillomavirus (HPV) vaccine in survivors of childhood and adolescent and young adult (AYA) cancer.

PURPOSE: To estimate the population-based incidence of HPV vaccination after childhood cancer. METHODS: Pediatric and young adult cancer survivors identified in the institutional Comprehensive Cancer Center registry were linked to the North Carolina Immunization Registry (NCIR). Initiation and completion of any HPV vaccine was evaluated in survivors born between 1984 and 2002 with an NCIR record by December 2014. Descriptive statistics and Kaplan-Meier estimates of cumulative incidence were stratified by sex and age at eligibility for vaccine. Cox proportional hazards were conducted and stratified by sex. RESULTS: Among 879 (n = 428 female; n = 451 male) study-eligible cancer survivors without prior HPV vaccination (n = 501 < 18 years, n = 378 ≥ 18 years at the time of eligibility), the cumulative incidence of HPV vaccine initiation following cancer therapy was 48.1% among females at 8.2 years and 29.2% among males at 5.0 years after vaccine eligibility among those < 18 years, and 6.2% among females at 8.1 years and 2.0% among males at 4.2 years after vaccine eligibility among those ≥ 18 years. Among those who initiated vaccination, 53% of females and 43% of males completed a 3-dose series. Younger age at cancer diagnosis (≤ 10 and 11-14 years vs. ≥ 15 years) and shorter interval from diagnosis to vaccine eligibility were more likely to initiate vaccination in models adjusted for age at eligibility, race/ethnicity, cancer type, relapse, and transplant. CONCLUSIONS: Despite the benefit of a cancer prevention strategy, cancer survivors are sub-optimally vaccinated against HPV. IMPLICATIONS FOR CANCER SURVIVORS: Immunization registries can help oncologists and primary care providers identify gaps in vaccination and target HPV vaccine delivery in survivors.