European journal of cancer : official journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
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The regulatory route leading to the definition of therapeutic indications of new compounds as well as extensions of indication (EoI) of already approved ones is a challenging process. If new anticancer drugs reach the market with a lack of complete evidence, this usually leads regulators to request additional data, post approval commitments or restrictions in therapeutic indications. This study aims at quantifying the time needed for anticancer drugs approved by the EMEA to get an extension, the rates and characteristics of extensions approved, and at exploring the regulatory process leading to the definition of new indications. ⋯ The other two types of indication broadening refer to a different tumour stage (8%) and to the inclusion of a new patient population (7%). The analysis of indication restrictions showed that in 20 cases out of 50 (40%) therapeutic indications were restricted by the Committee for Medicinal Products for Human Use (CHMP) during the assessment, with 60% of the restrictions occurring in 2006-2007. This study adds three main pieces of information: (i) the majority of anticancer drugs still have a single indication regardless of the year of approval; (ii) the time needed to obtain an extension of indication has decreased significantly over the last decade and (iii) a highest rate of regulatory restrictions is matched to shorter clinical developments.
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NVP-AUY922, a potent heat shock protein (HSP) 90 inhibitor, downregulates the expression of many oncogenic proteins, including the human epidermal growth factor receptor-2 (HER2). Because HER2 downregulation is a potential biomarker for early response to HSP90-targeted therapies, we used the (89)Zr-labelled HER2 antibody trastuzumab to quantify the alterations in HER2 expression after NVP-AUY922 treatment with HER2 positron emission tomography (PET) imaging. The HER2 overexpressing human SKOV-3 ovarian tumour cell line was used for in vitro experiments and as xenograft model in nude athymic mice. ⋯ PET results were confirmed by ex-vivo (89)Zr-trastuzumab biodistribution and HER2 immunohistochemical staining. NVP-AUY922 effectively downregulates HER2, which can be monitored and quantified in vivo non-invasively with (89)Zr-trastuzumab PET. This technique is currently under clinical evaluation and might serve as an early biomarker for HSP90 inhibition in HER2 positive metastatic breast cancer patients.
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Randomized Controlled Trial Multicenter Study
Dose-intensified epirubicin versus standard-dose epirubicin/cyclophosphamide followed by CMF in breast cancer patients with 10 or more positive lymph nodes: results of a randomised trial (GABG-IV E-93) - the German Adjuvant Breast Cancer Group.
To compare dose-intensified epirubicin monotherapy with a standard sequential regimen, patients with primary breast cancer and > or =10 involved axillary nodes were randomised to either four 21-day cycles of epirubicin 120 mg/m(2) (E120; n=202) or four 21-day cycles of epirubicin 90 mg/m(2) plus cyclophosphamide 600 mg/m(2) (EC) followed by three 28-day cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF; n=209). Simultaneous hormonal treatment was applied in both arms. ⋯ E120 was as effective as EC-CMF with regard to EFS (hazard ratio [HR] for E120 versus EC-CMF 1.04; 95% CI, 0.79-1.36; p=0.79) and overall survival (HR 1.06; 95% CI 0.77-1.46; p=0.72). The data demonstrate that 4 cycles of dose-intensified epirubicin monotherapy can be as effective as 7 cycles of standard sequential polychemotherapy in high-risk breast cancer patients with > or =10 positive lymph nodes, despite treatment with a single agent and a shorter treatment duration.
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Randomized Controlled Trial Multicenter Study
A randomised, controlled trial of the psychological effects of reflexology in early breast cancer.
To conduct a pragmatic randomised controlled trial (RCT) to evaluate the effects of reflexology on quality of life (QofL) in women with early breast cancer. ⋯ When compared to SIS, reflexology and massage have statistically significant, and, for reflexology, clinically worthwhile, effects on QofL following surgery for early breast carcinoma.
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Multicenter Study Clinical Trial
Primary postoperative chemotherapy without radiotherapy for treatment of brain tumours other than ependymoma in children under 3 years: results of the first UKCCSG/SIOP CNS 9204 trial.
Radiotherapy is an effective adjuvant treatment for brain tumours arising in very young children, but it has the potential to damage the child's developing nervous system at a crucial time - with a resultant reduction in IQ leading to cognitive impairment, associated endocrinopathy and risk of second malignancy. We aimed to assess the role of a primary chemotherapy strategy in avoiding or delaying radiotherapy in children younger than 3 years with malignant brain tumours other than ependymoma, the results of which have already been published. ⋯ The outcome for very young children with brain tumours is dictated by degree of surgical resection and histological tumour type and underlying biology as an indicator of treatment sensitivity. Overall, the median age at radiotherapy was 3 years and radiotherapy was avoided in 45% of patients. Desmoplastic/nodular sub-type of medulloblastoma has a better prognosis than classic histology, despite traditional adverse clinical features of metastatic disease and incomplete surgical resection. A subgroup with HGG and CPC are long-term survivors without RT. This study highlights the differing therapeutic challenges presented by the malignant brain tumours of early childhood, the importance of surgical approaches and the need to explore individualised brain sparing approaches to the range of malignant brain tumours that present in early childhood.