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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Cancer stem cells (CSCs), i.e. cancer cells that can self-renew, constitute only a minority of the cells of a tumour, but, because of their ability to initiate and repopulate tumours, failure to control CSCs can potentially lead to tumour re-growth, even though the bulk tumour may have been treated successfully. Nanomedicines improve spatio-temporal control over drug kinetics and distribution, thus opening the prospect of safer and more specific therapies to address the challenges posed by CSCs. In particular, these systems have the potential to facilitate CSC-aware therapy by overcoming resistance to conventional cytotoxic drugs and by targeting novel therapies to the tumour and CSC-marker positive cells. This review examines the implications of the CSC paradigm specifically for the development of nanomedicines, i.e. therapies based on macromolecules or supramolecular aggregates.
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Review Meta Analysis
RECIST revisited: a review of validation studies on tumour assessment.
The response evaluation criteria in solid tumours (RECIST) was developed in the late 1990s to replace the WHO criteria for response evaluation. The new criteria included important changes such as unidimensional tumour measurement, selection of target lesions with a minimum size, details concerning imaging modalities and a new threshold for assignment of objective progression. RECIST was published in February 2000 and very quickly came into operation first in clinical trials performed under the auspices of EORTC, US NCI or NCI Canada Clinical Trials Group but was adopted quickly thereafter by the entire cancer clinical research community. ⋯ Furthermore, anatomical changes in the tumour as described by RECIST may be detected later than functional changes in some circumstances, as for example in Gastro-Intestinal Stromal Tumours treated with Imatinib. However, there is no other universal method of tumour assessment as yet and functional imaging methods have not been validated and will not be widely available for some time. The findings of this review, together with experience acquired thus far and the results of some ongoing research projects, have paved the way for RECIST 2.0 to be hopefully announced later this year.
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Randomized Controlled Trial
KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours.
A recent randomized EORTC phase III trial, comparing two doses of imatinib in patients with advanced gastrointestinal stromal tumours (GISTs), reported dose dependency for progression-free survival. The current analysis of that study aimed to assess if tumour mutational status correlates with clinical response to imatinib. Pre-treatment samples of GISTs from 377 patients enrolled in phase III study were analyzed for mutations of KIT or PDGFRA by combination of D-HPLC and direct sequencing of tumour genomic DNA. ⋯ In patients whose tumours expressed an exon 9 KIT oncoprotein, treatment with the high-dose regimen resulted in a significantly superior progression-free survival (P=0.0013), with a reduction of the relative risk of 61%. We conclude that tumour genotype is of major prognostic significance for progression-free survival and overall survival in patients treated with imatinib for advanced GISTs. Our findings suggest the need for differential treatment of patients with GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug.
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Randomized Controlled Trial Comparative Study
A randomised phase II study of two different schedules of pegylated liposomal doxorubicin in metastatic breast cancer (EORTC-10993).
One hundred and sixteen women with measurable metastatic breast cancer participated in a randomised phase II study of single agent liposomal pegylated doxorubicin (Caelyx) given either as a 60 mg/m2 every 6 weeks (ARM A) or 50 mg/m2 every 4 weeks (ARM B) schedule. Patients were over 65 years of age or, if younger, had refused or been unsuitable for standard anthracyclines. The aims of the study were to evaluate toxicity and dose delivery with the two schedules and obtain further information on the response rate of liposomal pegylated doxorubicin as a single agent in anthracycline nai ve advanced breast cancer. ⋯ Confirmed objective partial responses by RECIST criteria were seen with both schedules; 15/51 (29%) on ARM A and 17/56 (31%) on ARM B. Liposomal pegylated doxorubicin showed significant activity in advanced breast cancer with a generally favourable side-effect profile. The high frequency of stomatitis seen with 6 weekly treatment makes this the less preferred of the two schedules tested.
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Comparative Study
Assessing health-related quality of life in palliative care: comparing patient and physician assessments.
It is often difficult to recruit patients for palliative care studies and severe attrition must be expected resulting in biased findings. This may be avoided if equivalent information could be obtained from sources other than the patients. Therefore, we investigated whether physician assessments can be used to evaluate the patients' health-related quality of life (HRQOL). ⋯ Physicians reported patients to have fewer problems/symptoms than patients did for all HRQOL domains except for physical and social functioning. The agreement between patients and physicians was poor. Using physician assessments may bias findings and cannot be recommended as a substitute for patient self-assessment in palliative care.