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Manchester, United Kingdom

Judson I.,Sarcoma Unit | Scurr M.,Sarcoma Unit | Gardner K.,Sarcoma Unit | Barquin E.,Sarcoma Unit | And 6 more authors.
Clinical Cancer Research | Year: 2014

Purpose: Cediranib is a potent VEGF signaling inhibitor with activity against all three VEGF receptors and KIT. This phase II study evaluated the antitumor activity of cediranib in patients with metastatic gastrointestinal stromal tumor (GIST) resistant/intolerant to imatinib, or metastatic soft-tissue sarcomas (STS; ClinicalTrials.gov, NCT00385203). Experimental Design: Patients received cediranib 45 mg/day. Primary objective was to determine the antitumor activity of cediranib according to changes in 2[18F]fluoro-2-deoxy-D-glucose positron emission tomography (18FDG-PET) tumor uptake in patients with GIST using maximum standardized uptake values (SUVmax). Secondary objectives included objective tumor response and tolerability in patients with GIST/STS. Results: Thirty-four of 36 enrolled patients were treated (GIST n = 24; STS n = 10). At day 29, five patients had confirmed decreases in SUVmax (≥ 10% from day 8) and two had confirmed partial metabolic responses (≥25% decrease), but arithmetic mean percentage changes in SUVmax, averaged across the cohort, were not significant at day 8 [6.8%; 95% confidence interval (CI), 19.95-33.54) or day 29 (4.6%; 95% CI, 8.05-17.34). Eleven patients with GIST achieved a best objective tumor response of stable disease; eight achieved stable disease ≥16 weeks. In patients with STS, four of six with alveolar soft-part sarcoma (ASPS) achieved confirmed and durable partial responses. The commonest adverse events were diarrhea (85%), fatigue (74%), and hypertension (68%). Conclusions: In patients progressing on imatinib/sunitinib, cediranib 45 mg/day demonstrated evidence of activity by18FDG-PET, but did not reduce average SUVmax. Evidence of antitumor activity was seen in ASPS. © 2014 American Association for Cancer Research.

Kirkwood J.M.,University of Pittsburgh | Lorigan P.,Christie Hospital NHS Foundation Trust | Hersey P.,University of Newcastle | Hauschild A.,University of Kiel | And 6 more authors.
Clinical Cancer Research | Year: 2010

Purpose: This phase II study assessed the antitumor activity of tremelimumab, a fully human, anti-CTL-associated antigen 4 monoclonal antibody, in patients with melanoma. Experimental Design: Patients with refractory/relapsed melanoma received 15 mg/kg tremelimumab every 90 days. After 4 doses, patients with tumor response or stable disease were eligible to receive ≤4 additional doses. Primary endpoint was best overall tumor response assessed by an independent endpoint review committee, and secondary endpoints included duration of response, overall survival, progression-free survival, and safety. Results: Of 251 patients enrolled, 246 (241 response-evaluable) received tremelimumab. Objective response rate was 6.6% (16 partial responses); duration of response was 8.9 to 29.8 months. Eight (50%) objective responses occurred in patients with stage IV M1c disease, and 11 (69%) were ongoing at last tumor assessment. Eight (3.3%) patients achieved responses in target lesions (Response Evaluation Criteria in Solid Tumors) despite progressive disease within the first cycle. All 8 survived for >20 months; 5 (63%) remained alive. Clinical benefit rate (overall response + stable disease) was 21% (16 partial responses and 35 stable disease), and median overall survival was 10.0 months. Progression-free survival at 6 months was 15%, and survival was 40.3% at 12 months and 22% at 24 months. Common treatment-related adverse events were generally mild to moderate, and grade 3/4 adverse events included diarrhea (n = 28, 11%), fatigue (n = 6, 2%), and colitis (n = 9, 4%). There were 2 (0.8%) treatment-related deaths. Conclusions: Tremelimumab showed an objective response rate of 6.6%, with all responses being durable ≤170 days since enrollment, suggesting a potential role for tremelimumab in melanoma. ©2010 AACR.

Addison J.,Education Center Library | Glover S.W.,Christie Hospital NHS Foundation Trust | Thornton C.,University of Manchester
Health Information and Libraries Journal | Year: 2010

Background: Most NHS library services routinely offer both mediated searches and information skills training sessions to their users. We analyse the impact of these two services on the amount of literature searching demonstrated by users of hospital- based library services in the north-west of England. Methods: Data for (1) mediated literature searches, (2) number of library users attending information skills training sessions, (3) amount of library staff time devoted to information skills training, and (4) number of Athens-authenticated log-ins to databases were obtained from statistical returns for 2007, and analysed for significant correlations. Results: There was evidence of quite strong correlations between the two measures of training activity and the number of mediated literature searches performed by library staff. There was weaker evidence of correlation between training activity and total literature searching activity. Discussion: Attending training sessions may make some library users aware of the difficulty of complex literature searches and actually reduce their confidence to perform their own complex searches independently. The relationships between information skills training, mediated literature searches, and independent literature searching activity remain complex. © 2010 Health Libraries Group.

Cawley D.,Christie Hospital NHS Foundation Trust | Waterman D.,St Anns Hospice | Roberts D.,St Anns Hospice | Caress A.L.,University of Manchester
Palliative Medicine | Year: 2011

Palliative care exists in a variety of settings and palliative care teams form many guises within this. A Palliative Medicine Outpatient Clinic (PMOC) exists to meet the flexible provision of the needs and preferences of individuals within whatever care setting they reside. This explorative study used a qualitative methodology, capturing patients' actual experience of care in preference to their satisfaction, as this is a more accurate measure of how and what patients judge as important in their healthcare. The overall themes in this paper point to the 'value' that patients perceived from attending the PMOC and how important the clinics were to clinicians that provided the care. The clinic facilitates much more than symptom control and here lies the challenge in how we convert the very positive experience of individuals into a language of outcome measures that captures the 'essence' of our work in this fiscally driven health economy. © 2011 The Author(s).

Valle J.W.,Christie Hospital NHS Foundation Trust | Eatock M.,Northern Ireland Cancer Center | Clueit B.,Pfizer | Gabriel Z.,Pfizer | And 2 more authors.
Cancer Treatment Reviews | Year: 2014

Introduction: Pancreatic neuroendocrine tumours (pNETs) are rare and the majority of patients present with advanced disease. Such patients have limited treatment options. We conducted a systematic review of published clinical trials of non-surgical interventions in pNET, to understand the efficacy, safety and health related quality of life (HRQoL) outcomes from the current evidence base. Methods: Electronic databases and manual bibliographic searches were conducted to identify relevant studies. Data were extracted by two independent reviewers. Results: Forty seven clinical studies met the predefined inclusion criteria. The following interventions were included: targeted therapies (two RCTs and six single-arm studies), chemotherapy (two RCTs, one prospective nonrandomised, comparative study and 14 single-arm studies);somatostatin analogues (SSA) and radiolabeled SSA therapies (nine single-arm studies), liver-directed therapies (six single-arm studies), mixed treatment regimens (one RCT, four single-arm studies) and other interventions such as interferon and recombinant human endostatin (one single-arm study for each). The paucity of RCT data and lack of consistency in reporting validated study outcomes and differing patient inclusion criteria between studies made it difficult to compare the relative efficacy of therapies. Discussion: The majority of published studies assessing treatment regimens for the management of pNET are single arm, non-randomised studies, often enrolling a small number of patients and not reporting clinically meaningful outcomes. However data from recently conducted studies assessing targeted therapies indicate that it is possible to conduct adequately powered RCTs reporting standardised oncological endpoints in this rare cancer. Further, similarly robust studies should be conducted to define the optimal treatment algorithm. © 2013 The Authors.

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