RESUMEN
Objectives: To test the feasibility of a randomised controlled trial (RCT) of aspirin and/or vitamin D3 in active surveillance (AS) low/favourable intermediate risk prostate cancer (PCa) patients with Prolaris® testing. Patients and Methods: Newly-diagnosed low/favourable intermediate risk PCa patients (PSA ≤ 15 ng/ml, International Society of Urological Pathology (ISUP) Grade Group ≤2, maximum biopsy core length <10 mm, clinical stage ≤cT2c) were recruited into a multi-centre randomised, double-blind, placebo-controlled study (ISRCTN91422391, NCT03103152). Participants were randomised to oral low dose (100 mg), standard dose (300 mg) aspirin or placebo and/or vitamin D3 (4000 IU) versus placebo in a 3 × 2 factorial RCT design with biopsy tissue Prolaris® testing. The primary endpoint was trial acceptance/entry rates. Secondary endpoints included feasibility of Prolaris® testing, 12-month disease re-assessment (imaging/biochemical/histological), and 12-month treatment adherence/safety. Disease progression was defined as any of the following (i) 50% increase in baseline PSA, (ii) new Prostate Imaging-Reporting and Data System (PI-RADS) 4/5 lesion(s) on multi-parametric MRI where no previous lesion, (iii) 33% volume increase in lesion size, or radiological upstaging to ≥T3, (iv) ISUP Grade Group upgrade or (v) 50% increase in maximum cancer core length. Results: Of 130 eligible patients, 104 (80%) accepted recruitment from seven sites over 12 months, of which 94 patients represented the per protocol population receiving treatment. Prolaris® testing was performed on 76/94 (81%) diagnostic biopsies. Twelve-month disease progression rate was 43.3%. Assessable 12-month treatment adherence in non-progressing patients to aspirin and vitamin D across all treatment arms was 91%. Two drug-attributable serious adverse events in 1 patient allocated to aspirin were identified. The study was not designed to determine differences between treatment arms. Conclusion: Recruitment of AS PCa patients into a multi-centre multi-arm placebo-controlled RCT of minimally-toxic adjunctive oral drug treatments with molecular biomarker profiling is acceptable and safe. A larger phase III study is needed to determine optimal agents, intervention efficacy, and outcome-associated biomarkers.
RESUMEN
PURPOSE: Tamoxifen is an effective drug, but its role in prevention is limited by its adverse effect profile. Non-life-threatening adverse effects, such as vasomotor symptoms, have an important influence in its use for prevention. Vasomotor symptoms were evaluated according to follow-up time, severity, and use of hormone replacement therapy (HRT) in a retrospective analysis. PATIENTS AND METHODS: In the International Breast Cancer Intervention Study-I study, 7,154 women at increased risk of breast cancer were randomly assigned to either tamoxifen 20 mg/d or placebo for 5 years. Women gave detailed information on any vasomotor symptoms at each 6-month follow-up visit. RESULTS: Hot flushes were reported more often in the tamoxifen group than in the placebo group (70.6% v 57.1%, respectively; odds ratio, 1.80; 95% CI, 1.63 to 1.99). Severe hot flushes were more strongly related to tamoxifen. In the tamoxifen arm, more women taking HRT at entry experienced hot flushes in the first 6 months than those who did not take HRT (60.8% v 49.2%, respectively; P = .09). In contrast, women on placebo taking HRT at entry experienced fewer hot flushes than women who stopped HRT (22.9% v 34.3%, respectively; P = .03). Furthermore, for women who first began HRT in the first 6 months of the trial compared with women who did not begin HRT, HRT seemed to be much more effective in controlling hot flushes in months 6 to 12 in the placebo arm (47.9% v 20.4%, respectively) than in the tamoxifen arm (51.4% v 39.0%, respectively). CONCLUSION: HRT use at entry or during the trial was not effective in alleviating hot flushes for women in the tamoxifen arm. Our retrospective study suggests that estrogen-based HRT has limited effectiveness among women receiving tamoxifen.
