Nonmelanoma skin cancers, such as basal-cell carcinoma and squamous-cell carcinoma, are common cancers that are caused principally by ultraviolet (UV) radiation. Nicotinamide (vitamin B3) has been shown to have protective effects against damage caused by UV radiation and to reduce the rate of new premalignant actinic keratoses.
Objective To compare the clinical effectiveness and patient acceptance of a large spacer device (Nebuhaler™) for delivery of metered dose aerosol (MDI) terbutaline with nebulised wet aerosol terbutaline. Design Randomised open crossover study over two sequential four week treatment periods, following a two week run-in. Setting Multi-centre including five adult thoracic units and three paediatric centres throughout Australia. Patients Thirty-eight adults and 23 children with clinical asthma and reversible airflow obstruction (increase in forced expiratory volume in one second [FEV1] of ≥15% in response to inhaled bronchodilator) entered the study proper. Six adults and one child withdrew. Interventions Terbutaline was administered four times dialy via Nebuhaler/MDI or nebuliser. Clinical assessment with spirometry and peak flow readings was made after run-in and at the end of each treatment period. Patients recorded on diary cards daily peak expiratory flow rates and symptom scores and comparisons of these results for each treatment period were made. At the completion of the study patients answered a treatment preference questionnaire. Results No differences were found between the two treatment periods in diary card peak flow recordings and symptom score data, and in clinical assessment of spirometry and peak expiratory flow rates. There were also no differences between spirometry and peak flow values recorded at the clinic at randomisation and at the end of each treatment period, suggesting stable basal airflow obstruction over the period of the study. Thirty-two per cent of adults and 52% of children preferred the Nebuhaler/MDI combination, mainly because of convenience of use. Treatment preference was not related to any measured index of lung function. Conclusions MDI terbutaline delivered via Nebuhaler provides clinical benefit similar to that of wet aerosol terbutaline in the long-term domiciliary management of patients with stable airflow obstruction.
1703 Objectives: 177Lu-PSMA-617 is a radiolabelled small molecule that delivers β-radiation to cells expressing prostate specific membrane antigen (PSMA), with promising activity and safety in metastatic castration-resistant prostate cancer (mCRPC). We compared 177Lu-PSMA-617 and cabazitaxel in a randomised phase 2 trial.
Methods: Men with mCRPC progressing after docetaxel with high PSMA tumour-expression were randomized to 177Lu-PSMA-617 (6-8.5 GBq intravenously 6 weekly up to 6 cycles) vs cabazitaxel (20 mg/m2 intravenously 3 weekly up to 10 cycles) at 11-sites in Australia. The primary endpoint was prostate specific antigen (PSA) response rate defined by ≥50% reduction (PSA50-RR). Secondary endpoints included progression-free survival (PFS) (PSA and radiographic PFS), objective response rate (ORR) (RECIST 1.1), adverse events (CTCAE v4.03), patient-reported outcomes (PROs) (EORTC QLQ-C30, PDF), and overall survival (OS). This trial is registered in ClinicalTrials.gov, NCT03392428.
Results: 200 of 291 men identified as eligible on PET imaging were randomised to 177Lu-PSMA-617 (N=99) or cabazitaxel (N=101). 91% had received prior androgen receptor-directed therapy (ARDT). PSA50-RR was significantly higher in those assigned 177Lu-PSMA-617 versus cabazitaxel (66% [95%CI,56-75%] vs 37% [95%CI,27-46%]; P<0.001). PFS was significantly longer in those assigned 177Lu-PSMA-617 than cabazitaxel (rates at 1yr 19% [95%CI,12-27%] vs 3% [95%CI,1-9%], hazard ratio (HR) 0·63 [95%CI,0.46-0.86; P=0.003). ORR in 78 men with measurable disease was significantly higher with 177Lu-PSMA-617 than cabazitaxel (49% vs 24%, RR 2.12; P=0.026). Follow-up remains immature for OS. Grade 3-4 adverse events occurred in 32/98 (33%) with 177Lu-PSMA-617 vs 45/85 (55%) with cabazitaxel. Overall quality-of-life and health status were similar, with significantly better outcomes for multiple PRO domains including diarrhoea, fatigue, social functioning, insomnia, hair loss, skin rash and sore hands/feet with 177Lu-PSMA-617.
Conclusions: 177Lu-PSMA-617 compared to cabazitaxel in men with mCRPC led to significantly higher PSA and ORR response rates, longer PFS, less grade 3 or 4 adverse events and significant improvements in several PRO domains.
Acknowledgements: This investigator-initiated trial received support from the Prostate Cancer Foundation of Australia, Endocyte (a Novartis Company), Australian Nuclear Science and Technology Organization (ANSTO), Movember, It’s a Bloke Thing, CAN4CANCER. Results also presented at ASCO GU 2021.
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