Publications

Intermittent androgen deprivation for prostate-specific antigen (PSA) elevation after radiotherapy may improve quality of life and delay hormone resistance. We assessed overall survival with intermittent versus continuous androgen deprivation in a noninferiority randomized trial.

Prostate cancer might have high radiation-fraction sensitivity, implying a therapeutic advantage of hypofractionated treatment. We present a pre-planned preliminary safety analysis of side-effects in stages 1 and 2 of a randomised trial comparing standard and hypofractionated radiotherapy.

Radiotherapy is an alternative to cystectomy in patients with muscle-invasive bladder cancer. In other disease sites, synchronous chemoradiotherapy has been associated with increased local control and improved survival, as compared with radiotherapy alone.

Xerostomia is the most common late side-effect of radiotherapy to the head and neck. Compared with conventional radiotherapy, intensity-modulated radiotherapy (IMRT) can reduce irradiation of the parotid glands. We assessed the hypothesis that parotid-sparing IMRT reduces the incidence of severe xerostomia.

Background: Recruitment to randomised controlled trials (RCTs) with very different treatment arms is often difficult. The ProtecT (Prostate testing for cancer and Treatment) study successfully used qualitative research methods to improve recruitment and these methods were replicated in five other RCTs facing recruitment difficulties. A similar qualitative recruitment investigation was undertaken in the SPARE (Selective bladder Preservation Against Radical Excision) feasibility study to explore reasons for low recruitment and attempt to improve recruitment rates by implementing changes suggested by qualitative findings.Methods: In Phase I of the investigation, reasons for low levels of recruitment were explored through content analysis of RCT documents, thematic analysis of interviews with trial staff and recruiters, and conversation analysis of audio-recordings of recruitment appointments. Findings were presented to the trial management group and a plan of action was agreed. In Phase II, changes to design and conduct were implemented, with training and feedback provided for recruitment staff.Results: Five key challenges to trial recruitment were identified in Phase I: (a) Investigators and recruiters had considerable difficulty articulating the trial design in simple terms; (b) The recruitment pathway was complicated, involving staff across different specialties/centres and communication often broke down; (c) Recruiters inadvertently used 'loaded' terminology such as 'gold standard' in study information, leading to unbalanced presentation; (d) Fewer eligible patients were identified than had been anticipated; (e) Strong treatment preferences were expressed by potential participants and trial staff in some centres. In Phase II, study information (patient information sheet and flowchart) was simplified, the recruitment pathway was focused around lead recruiters, and training sessions and 'tips' were provided for recruiters. Issues of patient eligibility were insurmountable, however, and the independent Trial Steering Committee advised closure of the SPARE trial in February 2010.Conclusions: The qualitative investigation identified the key aspects of trial design and conduct that were hindering recruitment, and a plan of action that was acceptable to trial investigators and recruiters was implemented. Qualitative investigations can thus be used to elucidate challenges to recruitment in trials with very different treatment arms, but require sufficient time to be undertaken successfully.

Background: The antiestrogen tamoxifen may have partial estrogen-like effects on the postmenopausal uterus. Aromatase inhibitors (AIs) are increasingly used after initial tamoxifen in the adjuvant treatment of postmenopausal early breast cancer due to their mechanism of action: a potential benefit being a reduction of uterine abnormalities caused by tamoxifen.Patients and methods: Sonographic uterine effects of the steroidal AI exemestane were studied in 219 women participating in the IntergroupExemestane Study: a large trial in postmenopausal women with estrogen receptor-positive (or unknown) early breast cancer, disease free after 2-3 years of tamoxifen, randomly assigned to continue tamoxifen or switch to exemestane to complete 5 years adjuvant treatment. The primary end point was the proportion of patients with abnormal (5 mm) endometrial thickness (ET) on transvaginal ultrasound 24 months after randomisation.Results: The analysis included 183 patients. Two years after randomisation, the proportion of patients with abnormal ET was significantly lower in the exemestane compared with tamoxifen arm (36% versus 62%, respectively; P = 0.004). This difference emerged within 6 months of switching treatment (43.5% versus 65.2%, respectively; P = 0.01) and disappeared within 12 months of treatment completion (30.8% versus 34.7%, respectively; P = 0.67).Conclusion: Switching from tamoxifen to exemestane significantly reverses endometrial thickening associated with continued tamoxifen.

Incorporation of a taxane as adjuvant treatment for early breast cancer offers potential for further improvement of anthracycline-based treatment. The UK TACT study (CRUK01/001) investigated whether sequential docetaxel after anthracycline chemotherapy would improve patient outcome compared with standard chemotherapy of similar duration.