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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Multicenter Study
Evolution of requests to hasten death among patients managed by palliative care teams in France: a multicentre cross-sectional survey (DemandE).
Strongly marked ideological positions on the impact of palliative care and limited hard data plague the debate on physician-assisted death. ⋯ The large number of described cases provides, for the first time, comprehensive hard data on the evolution of RHDs in a country that has not legalised euthanasia. Whatever the way RHD are expressed, they are frequently maintained despite adequate palliative care with suitable control of pain and psychological support by specialists.
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It can be difficult to identify endpoints that accurately reflect patient benefit in metastatic solid tumors. Overall survival (OS) is the gold standard although progression-free survival (PFS) is sometimes used as a surrogate for OS. Statistical modelling has suggested that the association between OS and PFS becomes weaker in diseases with longer survival post-progression (SPP). ⋯ Such endpoints have been successfully used in cancer trials in the past. With improvements in therapy and prolonged survival of patients with many cancers, and with increasing pressure from healthcare payers to prove that treatment leads to patient benefit, the choice of optimal endpoints for clinical trials is increasingly important. Composite measures comprising patient reported outcomes and intermediate endpoints such as PFS may be the solution and should be investigated further.
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Randomized Controlled Trial Multicenter Study
Everolimus in metastatic renal cell carcinoma: Subgroup analysis of patients with 1 or 2 previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapies enrolled in the phase III RECORD-1 study.
In the phase III RECORD-1 trial (ClinicalTrials.gov: NCT00410124), patients with metastatic renal cell carcinoma (mRCC) who progressed on previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor (VEGFr-TKI) therapy were randomised 2:1 to everolimus 10mg once daily (n=277) or placebo (n=139). Median progression-free survival (PFS) was 4.9months with everolimus and 1.9months with placebo (hazard ratio [HR], 0.33; P<.001). This preplanned, prospective sub-analysis evaluated PFS benefit of everolimus versus placebo in patients who had previously received 1 or 2 VEGFr-TKIs. ⋯ Everolimus was associated with prolonged PFS relative to placebo in patients who received 1 or 2 previous VEGFr-TKIs. Patients who received only 1 previous VEGFr-TKI had apparently longer PFS with everolimus in reference to those who received 2 previous VEGFr-TKIs. These results support the use of everolimus as the standard of care in patients who fail initial VEGFr-TKI therapy.
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Multicenter Study
A phase I and pharmacokinetic study of plitidepsin in children with advanced solid tumours: an Innovative Therapies for Children with Cancer (ITCC) study.
To determine the maximum tolerated dose, the recommended dose (RD) for phase II studies, dose-limiting toxicities and pharmacokinetics (PK) for plitidepsin administered as a 3-h intravenous infusion every 2weeks (one cycle) to children with refractory or relapsed solid tumours. ⋯ Plitidepsin administered to children as a 3-h infusion every 2weeks is received with manageable toxicity for children with cancer, and the RD is 5mg/m(2). Pharmacokinetic parameters in children and adolescents are comparable to adults. Future phase II studies of plitidepsin are warranted, and our results suggest that plitidepsin could be appropriately developed in combination with other antitumour where myelosuppression is dose-limiting.