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Port Glasgow, United Kingdom

Watson C.J.,University of Cambridge | Gusterson B.A.,Institute of Cancer science
Breast Cancer Research | Year: 2010

Cancer vaccines are the Holy Grail for patients and clinicians alike. The possibility that we can be vaccinated against common cancers is very appealing and the socioeconomic consequences are significant. A recent paper published in the journal Nature Medicine suggests a new approach for the development of a prophylactic vaccine for breast cancer. Their strategy was to induce mammary gland failure in mice by immunisation with an antibody specific to a milk protein that resulted in autoimmunity during lactation. This also showed some efficacy as a therapeutic vaccine. Can we look forward to the elimination of breast cancer? © 2010 BioMed Central Ltd.

Fizazi K.,University Paris - Sud | Scher H.I.,Sloan Kettering Cancer Center | Molina A.,Janssen Research and Development | Logothetis C.J.,University of Texas M. D. Anderson Cancer Center | And 14 more authors.
The Lancet Oncology | Year: 2012

Background: Abiraterone acetate improved overall survival in metastatic castration-resistant prostate cancer at a preplanned interim analysis of the COU-AA-301 double-blind, placebo-controlled phase 3 study. Here, we present the final analysis of the study before crossover from placebo to abiraterone acetate (after 775 of the prespecified 797 death events). Methods: Between May 8, 2008, and July 28, 2009, this study enrolled 1195 patients at 147 sites in 13 countries. Patients were eligible if they had metastatic castration-resistant prostate cancer progressing after docetaxel. Patients were stratified according to baseline Eastern Cooperative Oncology Group (ECOG) performance status, worst pain over the past 24 h on the Brief Pain Inventory-Short Form, number of previous chemotherapy regimens, and type of progression. Patients were randomly assigned (ratio 2:1) to receive either abiraterone acetate (1000 mg, once daily and orally) plus prednisone (5 mg, orally twice daily) or placebo plus prednisone with a permuted block method via an interactive web response system. The primary endpoint was overall survival, analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00091442. Findings: Of the 1195 eligible patients, 797 were randomly assigned to receive abiraterone acetate plus prednisone (abiraterone group) and 398 to receive placebo plus prednisone (placebo group). At median follow-up of 20·2 months (IQR 18·4-22·1), median overall survival for the abiraterone group was longer than in the placebo group (15·8 months [95% CI 14·8-17·0] vs 11·2 months [10·4-13·1]; hazard ratio [HR] 0·74, 95% CI 0·64-0·86; p<0·0001). Median time to PSA progression (8·5 months, 95% CI 8·3-11·1, in the abiraterone group vs 6·6 months, 5·6-8·3, in the placebo group; HR 0·63, 0·52-0·78; p<0·0001), median radiologic progression-free survival (5·6 months, 5·6-6·5, vs 3·6 months, 2·9-5·5; HR 0·66, 0·58-0·76; p<0·0001), and proportion of patients who had a PSA response (235 [29·5%] of 797 patients vs 22 [5·5%] of 398; p<0·0001) were all improved in the abiraterone group compared with the placebo group. The most common grade 3-4 adverse events were fatigue (72 [9%] of 791 patients in the abiraterone group vs 41 [10%] of 394 in the placebo group), anaemia (62 [8%] vs 32 [8%]), back pain (56 [7%] vs 40 [10%]), and bone pain (51 [6%] vs 31 [8%]). Interpretation: This final analysis confirms that abiraterone acetate significantly prolongs overall survival in patients with metastatic castration-resistant prostate cancer who have progressed after docetaxel treatment. No new safety signals were identified with increased follow-up. Funding: Janssen Research & Development. © 2012 Elsevier Ltd.

Makin G.,Institute of Cancer science
Paediatrics and Child Health (United Kingdom) | Year: 2014

Combination chemotherapy is the mainstay of treatment for most childhood cancer, either alone or in combination with surgery and radiotherapy. Sequential national and international studies of combinations of mostly well established cytotoxic drugs, with careful attention paid to the maintenance of dose intensity and the optimization of supportive care to manage acute toxicity, have resulted in dramatic improvements in the outcome for childhood cancer. Increased understanding of the molecular basis of childhood cancer will lead to the introduction of more targeted anti-cancer drugs, probably in combination with existing conventional agents. This will allow the remaining stubbornly drug-resistant childhood cancers to be treated more effectively, but will also allow does reduction of conventional agents in sensitive tumour types, reducing both acute and chronic toxicity. Increasing understanding of both pharmacokinetics and pharmacogenomics offers the opportunity for more personalized anti-cancer treatment, to optimize drug dosing for an individual, and to reduce their toxicity. © 2013 Elsevier Ltd.

Andreassen C.N.,Aarhus University Hospital | Dikomey E.,University of Hamburg | Parliament M.,Cross Cancer Institute | West C.M.L.,Institute of Cancer science
Radiotherapy and Oncology | Year: 2012

The ability to predict individual risk of radiation-induced normal tissue complications is a long sought goal in radiobiology. The last decade saw increasing interest in identifying associations between single nucleotide polymorphisms (SNPs) and normal tissue complication risk. Nevertheless, it remains controversial whether SNPs will be useful predictors of normal tissue radiosensitivity. This paper provides a summary of a scientific debate held at the 31st ESTRO conference in which four scientists argued in favor or against the motion that SNPs will be useful predictors of normal tissue radiosensitivity in the future. © 2012 Elsevier Ireland Ltd. All rights reserved.

Tait C.,Christie NHS Foundation Trust | Moore D.,University of Manchester | Hodgson C.,University of Manchester | Brown M.,Institute of Cancer science | And 7 more authors.
BJU International | Year: 2014

Results Patients with a higher metastasis number had a shorter PFS and OS (hazard ratio [HR] 2.0, 95% confidence interval [CI] 1.7-2.4; P < 0.001). Patients with 1-4 metastases had much better PFS and OS than those with 5-20 metastases. The median PFS and OS in the latter was 10.9 (95% CI 8.4-12.8) and 22.1 (95% CI: 18.5-24.5) months, respectively. PFS and OS for patients with >20 metastases were shorter still [median 5.3 (95% CI 3.4-6.9) months and 13.3 (95% CI 11.3-17.6) months, respectively]. Dichotomising into cohorts with 1-4 and ≥5 metastases, the latter group had considerably poorer PFS [8.4 (95% CI 6.8-10.3) months; P < 0.001) and OS [18.7 (95% CI 17.5-22.1) months; P < 0.001].Conclusions Dichotomising patients with CRPC into cohorts with 1-4 or ≥5 skeletal metastases identifies a better and a worse cohort in a manner that is easy and clinically accessible. This simple method facilitates disease stratification and patient management, enabling clinicians to counsel patients more effectively about long-term outcomes and to help select intervention therapies more effectively.Objective To report a simplified and effective method for substratification of M1 castrate-resistant prostate cancer (CRPC) by correlating progression-free (PFS) and overall survival (OS) with simple quantification of skeletal metastases.Patients and Methods In all, 561 men with M1 CRPC were studied longitudinally. Individual bone scan disease burden, quantified by counting bone metastasis number, was correlated with clinical outcome using specific threshold points of 1-4, 5-20 and >20 detectable lesions. © 2014 The Authors.

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