A Prospective Randomised Trial to Determine the Effect of a Reduced Versus Standard Dose of Enzalutamide on Side Effects in Frail Patients with Prostate Cancer.

BACKGROUND AND OBJECTIVE: Enzalutamide is a potent androgen receptor signalling inhibitor, effectively used for the treatment of different stages of prostate cancer. Side effects occur frequently at the registered dose, whilst a lower dose might be equally effective. Therefore, the aim of this study is to determine the effect of a reduced dose of enzalutamide on side effects in frail patients with prostate cancer. METHODS: This multicentre randomised trial compared the standard enzalutamide dose of 160 mg once daily (OD) with a reduced dose of 120 mg OD in frail patients with prostate cancer. Fatigue, cognitive side effects, and depressive symptoms were measured by the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire, Functional Assessment of Cancer Therapy-Cognitive Function (FACT-Cog) questionnaire, and Geriatric Depression Scale-15 (GDS-15). Linear mixed-effect models were used to study differences in side effects over time between both groups. KEY FINDINGS AND LIMITATIONS: In total, 52 patients were included in the analysis (25 reduced dose and 27 standard dose). Patients treated with the reduced dose had significantly lower fatigue after 24 wk than those with the standard dose (difference FACIT-Fatigue 6.2; 95% confidence interval 1.4-11.0; p = 0.01). Patients treated with the reduced dose showed stable fatigue, cognitive side effects, and depressive symptoms over time, whilst patients with the standard dose showed significantly worse side effects after 24 wk than at baseline. CONCLUSIONS AND CLINICAL IMPLICATIONS: A reduced dose of enzalutamide results in less fatigue, cognitive side effects, and depressive symptoms in frail patients with prostate cancer than the standard dose, without any indication of interference with efficacy endpoints. PATIENT SUMMARY: In this report, we looked at the side effects of enzalutamide at two dose levels. We found that, in frail patients, three tablets a day result in less fatigue than four tablets a day. Patients treated with four tablets a day showed an increase in fatigue, cognitive side effects, and depression. We conclude that a lower dose of three tablets can be used to alleviate side effects without indications for less efficacy.

Predicting the need for further thrombosis diagnostics in suspected DVT is increased by using age adjusted D-dimer values.

INTRODUCTION: Negative D-dimer values combined with clinical decision rules by Wells can help in excluding the diagnosis deep vein thrombosis (DVT). However, with increasing age D-dimer levels increase, possibly leading to false positive results. MATERIALS AND METHODS: In this prospective study we compared the specificity and sensitivity of conventional D-dimer levels and age adjusted D-dimer levels in the diagnosis of DVT. We included 528 patients, all over 50years of age, of whom 117 had a DVT confirmed by duplex ultrasound. RESULTS AND CONCLUSION: Age adjusted D-dimer cut-off values had higher specificity compared to conventional D-dimer values (24.6% vs. 8.5%) as well as a higher negative predictive value (91,8% vs. 89,7%). Therefore we conclude that age adjusted D-dimer levels could be used to exclude the diagnosis of DVT. Ultimately this could lead to the performance of less duplex ultrasounds reducing health care costs and discomfort for the patient.