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vrijdag 19 oktober 2018

The Lancet: [Comment] A step towards dignity in life and death

[Comment] A step towards dignity in life and death
All too many patients with cancer will die in pain, fear, or confusion, or with goodbyes unsaid, having spent the last few months of their lives experiencing treatment-related adverse events. With most patients given the highest amount of chemotherapy treatment during their last months of life, it seems that we have forgotten that extension of life at any cost is a price not worth paying. If the goal of evidence-based medicine is the use of research for people to live their lives in the best possible health, surely we should also use research to establish how patients can also have the best possible death.
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[Articles] Frontline bortezomib, rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) versus rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) in transplantation-ineligible patients with newly diagnosed mantle cell lymphoma: final overall survival results of a randomised, open-label, phase 3 study
In the LYM-3002 study, the efficacy and safety of frontline bortezomib plus rituximab, cyclophosphamide, doxorubicin, and prednisone (VR-CAP) and rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) were compared in transplant-ineligible patients with untreated, newly diagnosed, mantle cell lymphoma. We report the final overall survival and safety outcomes for patients in the long-term follow-up phase after the primary progression-free-survival endpoint was met.
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[Comment] Genotype-guided fluoropyrimidine dosing: ready for implementation
More than 20 years have passed since dihydropyrimidine dehydrogenase (DPD; encoded by the gene DPYD) deficiency was first described as a pharmacogenetic syndrome, which puts patients with reduced activity of this key catabolic enzyme at risk of toxicity from fluoropyrimidine-based chemotherapy.1 More recently, understanding of the effect of DPYD variants on the risk of fluoropyrimidine-related toxicity has improved immensely. For four DPYD variants known to confer reduced DPD activity,2 a recent meta-analysis3 confirmed their association with severe fluoropyrimidine-related toxicity.
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[Articles] DPYD genotype-guided dose individualisation of fluoropyrimidine therapy in patients with cancer: a prospective safety analysis
Prospective DPYD genotyping was feasible in routine clinical practice, and DPYD genotype-based dose reductions improved patient safety of fluoropyrimidine treatment. For DPYD*2A and c.1679T>G carriers, a 50% initial dose reduction was adequate. For c.1236G>A and c.2846A>T carriers, a larger dose reduction of 50% (instead of 25%) requires investigation. Since fluoropyrimidines are among the most commonly used anticancer agents, these findings suggest that implementation of DPYD genotype-guided individualised dosing should be a new standard of care.
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[Comment] Bortezomib-based chemotherapy in mantle cell lymphoma
Management of patients with newly diagnosed mantle cell lymphoma is fairly well established. For younger patients, treatment involves high-dose cytarabine-based chemotherapy, which is usually consolidated with stem-cell transplantation and rituximab maintenance therapy. For older patients, in whom high-intensity therapy is inappropriate, immuno-chemotherapy is the treatment of choice, and is usually based on either CHOP-based (cyclophosphamide, doxorubicin, vincristine, and prednisone) or bendamustine-based therapies.
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