24 3. Patient Prole Factors important in choice of therapy include • ECOG performance status • The presence of co-morbid disease including cardiovascular events, pre-existing hypertension, or uncontrolled seizures. These may inuence the choice of drug therapy. • The presence of secondary malignancies • Patient preference: Dosing preference, route of administration, pre/post prandial dosing, side effects, frequency and type of monitoring, cost, and accessibility of treatment. These are factors that may inuence patient decision making. 4. Molecular heterogeneity Recent data supports the heterogeneity of prostate cancer on a translational level and may account for the variable rates of disease progression in patients presenting with metastatic disease. This may guide treatment selection in the future. 5. Location of distant metastasis The site and number of metastatic deposits should guide treatment options and, is predictive of outcome. Patients presenting with de novo low volume metastatic disease may be offered local therapy based on the results of phase III data. Metastases directed therapies including radiotherapy are an option in patients with low volume metachronous metastatic disease. 6. Symptomatic vs asymptomatic disease • Combination therapy should be initiated early in the treatment of mHSPC. Systemic therapy should not be delayed even if asymptomatic as this has been shown to result in inferior outcomes. ADT alone should only be reserved for very selected cases (poor performance status, limited life expectancy). 7. Doublet vs Triplet therapy • Doublet therapy (ADT and Docetaxel or ADT and ART) should be initiated early in the diagnosis of mHSPC and is associated with improved outcomes. • Treatment intensication ie. combining ADT, Docetaxel and ART has been found to improve overall survival in patients with high volume metastatic disease when compared to doublet options. Dr van der Merwe summarized his talk with clear take home messages as follows: • ADT alone is no longer standard of care in the treatment of mHSPC. • Patient quality of life is maintained with therapy intensication. • Triplet therapy is appropriate for high volume, de novo mHSPC. Professor Bertrand Tombal (Chairman of the Department of Surgery and Full Professor of Urology at the Université catholique de Louvain (UCL), Cliniques universitaires Saint-Luc, Brussels, Belgium) provided a practical guide for clinicians when commencing a patient on enzalutamide. His recommendations are as follows: 1. Check for co-morbidities and identify potential drug-drug interactions. Engage with Pharmacists, cardiologists or treating physicians where necessary. Patient education is important. 2. Dosage of enzalutamide is 40 mg x 4 (160 mg) capsules a day and can be given before or after meals. Monitoring remains unchanged – PSA, testosterone levels, standard metabolic monitoring. No additional tests are required. 3. Side Effects • Enzalutamide is contraindicated in patients with a history of seizure or patients on medication that may lower the threshold for seizures. • Patients with a history of cardiovascular disease, should be closely monitored. • Adverse events: Mainly grade 1 or 2 have been reported in clinical trials. Based on the results of the ARCHES study, 5% of patients on the placebo arm and 7% on the enzalutamide arm discontinued treatment. There was a minimal increase in toxicity, with the exception of fatigue. 4. Fatigue • Is a common side effect of ADT therapy alone. a. Most patients treated with enzalutamide do not experience signicant worsening of fatigue. b. Often observed in the rst 13 weeks of treatment and improves with time. c. Nighttime dosing and regular exercise may help relieve symptoms of fatigue. 5. Monitor Patients for cardiovascular disease. Extra monitoring is required when enzalutamide is coadministered with an anticoagulant metabolized by CYP2C9 e.g warfarin. 6. Patients should be monitored for fracture risk. Bisphosphonates should be included as part of systemic therapy. The meeting was closed by Professor Shingai Mutambirwa, who emphasized the importance of early, appropriate management of patients with mHSPC based on clinical factors, recent data and guideline recommendations. The focus should be individualized patient care. UROLOGY, URO-ONCOLOGY AND SEXOLOGY UPDATE
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