Cabozantinib Versus Mitoxantrone-prednisone in Symptomatic Metastatic Castration-resistant Prostate Cancer: A Randomized Phase 3 Trial with a Primary Pain Endpoint

Background: Bone metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) are associated with debilitating pain and functional compromise. Objective: To compare pain palliation as the primary endpoint for cabozantinib versus mitoxantrone-prednisone in men with mCRPC and symptomatic bone metastases using patient-reported outcome measures. Design, setting, and participants: A randomized, double-blind phase 3 trial (COMET-2; NCT01522443) in men with mCRPC and narcotic-dependent pain from bone metastases who had progressed after treatment with docetaxel and either abiraterone or enzalutamide. Intervention: Cabozantinib 60 mg once daily orally versus mitoxantrone 12 mg/m2 every 3 wk plus prednisone 5 mg twice daily orally. Outcome measurements and statistical analysis: The primary endpoint was pain response at week 6 confirmed at week 12 (≥30% decrease from baseline in patient-reported average daily worst pain score via the Brief Pain Inventory without increased narcotic use). The planned sample size was 246 to achieve ≥90% power. Results and limitations: Enrollment was terminated early because cabozantinib did not demonstrate any survival benefit in the companion COMET-1 trial. At study closure, 119 participants were randomized (cabozantinib: N =61; mitoxantrone-prednisone: N = 58). Complete pain and narcotic use data were available at baseline, week 6, and week 12 for 73/106 (69%) patients. There was no significant difference in the pain response with cabozantinib versus mitoxantrone-prednisone: the proportions of responders were 15%versus 17%,a −2%difference(95%confidenceinterval:−16%to11%, p = 0.8). Barriers to accrual included pretreatment requirements for a washout period of prior anticancer therapy and a narcotic optimization period to maximize analgesic dosing. Conclusions: Cabozantinib treatment did not demonstrate better pain palliation than mitoxantrone-prednisone in heavily pretreated patients with mCRPC and symptomatic bone metastases. Future pain-palliation trials should incorporate briefer timelines from enrollment to treatment initiation. Patient summary: Cabozantinib was not better than mitoxantrone-prednisone for pain relief in patients with castration-resistant prostate cancer and debilitating pain from bone metastases

Physiological, Psychological and Performance-Related Changes Following Physique Competition: A Case-Series

The purpose of this case-series was to evaluate the physiological, psychological and performance-related changes that occur during the postcompetition period. Participants included three male (34.3 ± 6.8 years, 181.6 ± 8.9 cm) and four female (29.3 ± 4.9 years, 161.4 ± 6.0 cm) natural physique athletes. Body composition (fat mass (FM) and fat-free mass (FFM); Skinfold), resting metabolic rate (RMR; indirect calorimetry), total body water (TBW; bioelectrical impedance analysis), sleep quality (PSQI; Pittsburgh Sleep Quality Index), quality of life measures (RAND SF36), menstrual irregularities, and knee extension performance were assessed 1–2 weeks prior to competition, and 4 weeks and 8–10 weeks postcompetition. Blood hormones (free triiodothyronine; T3, free thyroxine; T4, and leptin) were assessed at 1–2 weeks prior to competition and 8–10 weeks postcompetition. Participants tracked daily macronutrient intake daily for the duration of the study. Group-level data were analyzed using exploratory, one-tailed, nonparametric statistical tests. Bodyweight, FM, bodyfat%, RMR, and blood hormones (T3, T4, and leptin) increased significantly (p &lt; 0.05) at the group level. Relative (%Δ) increases in fat mass were associated with △RMR (τ = 0.90; p = 0.001) and △leptin (τ = 0.68; p = 0.02), and △leptin was associated with △RMR (τ = 0.59; p = 0.03). The time course for recovery appears to vary substantially between individuals potentially due to strategies implemented postcompetition.</jats:p

Physiological, Psychological and Performance-Related Changes Following Physique Competition: A Case-Series

The purpose of this case-series was to evaluate the physiological, psychological and performance-related changes that occur during the postcompetition period. Participants included three male (34.3 &plusmn; 6.8 years, 181.6 &plusmn; 8.9 cm) and four female (29.3 &plusmn; 4.9 years, 161.4 &plusmn; 6.0 cm) natural physique athletes. Body composition (fat mass (FM) and fat-free mass (FFM); Skinfold), resting metabolic rate (RMR; indirect calorimetry), total body water (TBW; bioelectrical impedance analysis), sleep quality (PSQI; Pittsburgh Sleep Quality Index), quality of life measures (RAND SF36), menstrual irregularities, and knee extension performance were assessed 1&ndash;2 weeks prior to competition, and 4 weeks and 8&ndash;10 weeks postcompetition. Blood hormones (free triiodothyronine; T3, free thyroxine; T4, and leptin) were assessed at 1&ndash;2 weeks prior to competition and 8&ndash;10 weeks postcompetition. Participants tracked daily macronutrient intake daily for the duration of the study. Group-level data were analyzed using exploratory, one-tailed, nonparametric statistical tests. Bodyweight, FM, bodyfat%, RMR, and blood hormones (T3, T4, and leptin) increased significantly (p &lt; 0.05) at the group level. Relative (%&Delta;) increases in fat mass were associated with △RMR (&tau; = 0.90; p = 0.001) and △leptin (&tau; = 0.68; p = 0.02), and △leptin was associated with △RMR (&tau; = 0.59; p = 0.03). The time course for recovery appears to vary substantially between individuals potentially due to strategies implemented postcompetition

Intermittent Energy Restriction Attenuates the Loss of Fat Free Mass in Resistance Trained Individuals. A Randomized Controlled Trial

There is a lack of research into how lean, resistance trained (RT) individuals respond to intermittent energy restricted diets. Therefore, we investigated body composition changes in RT-individuals during continuous energy restriction or intermittent restriction. A total of 27 males and females (25 ± 6.1 years; 169 ± 9.4 cm; 80 ± 15.6 kg) were randomized to a ~25% caloric restricted diet Refeed (RF; n = 13) or Continuous group (CN; n = 14) in conjunction with 4-days/week resistance training for 7-weeks. RF implemented two consecutive days of elevated carbohydrate (CHO) intake, followed by 5-days of caloric restriction each week. CN adhered to a continuous 7-week caloric restriction. Body mass (BM), fat mass (FM), fat-free mass (FFM), dry fat-free mass (dFFM), and resting metabolic rate (RMR) were assessed pre/post-diet. Both groups significantly reduced BM (RF: baseline = 76.4 ± 15.6 kg, post-diet = 73.2 ± 13.8 kg, Δ3.2 kg; CN: baseline = 83.1 ± 15.4 kg, post-diet = 79.5 ± 15 kg, Δ3.6 kg) and FM (RF: baseline = 16.3 ± 4 kg, post-diet = 13.5 ± 3.6 kg, Δ2.8 kg; CN: baseline = 16.7 ± 4.5 kg, post-diet = 14.4 ± 4.9 kg, Δ2.3 kg) with no differences between groups. FFM (RF: baseline = 60.1 ± 13.8 kg, post-diet = 59.7 ± 13.0 kg, 0.4 kg; CN: baseline = 66.4 ± 15.2 kg, post-diet = 65.1 ± 15.2 kg, Δ1.3 kg p = 0.006), dFFM (RF: baseline = 18.7 ± 5.0 kg, post-diet = 18.5 ± 4.5 kg, Δ0.2 kg; CN: baseline =21.9 ± 5.7 kg, post-diet = 20.0 ± 5.7 kg, Δ1.9 kg), and RMR (RF: baseline = 1703 ± 294, post-diet = 1665 ± 270, Δ38 kcals; CN: baseline = 1867 ± 342, post-diet = 1789 ± 409, Δ78 kcals) were better maintained in the RF group. A 2-day carbohydrate refeed preserves FFM, dryFFM, and RMR during energy restriction compared to continuous energy restriction in RT-individuals.</jats:p