Pharmacoeconomic Considerations in Treating Patients With Acute Leukaemia

Whereas individual cost-effectiveness analyses of new agents for acute leukaemia should be performed in target populations, any meaningful pharmacoeconomic evaluation of treatment options for this condition should include the many types of costs and outcomes in unselected, representative groups of patients. Both direct costs (e.g. costs for medication and hospitalisation) and indirect costs (e.g. lost productivity costs and reduced quality of life) are important parameters to assess, as are the costs of chronic adverse effects, research and development costs for new agents, and costs of procedure-related deaths. Complete remission, cure and survival are the `success' response criteria for acute leukaemia treatments, in addition to prolonged life with acceptable quality of life for patients with incurable acute leukaemia. Death is `failure', caused either by resistant disease (relapse and progressive disease) inspite of optimal chemotherapy or, sometimes, by insufficient treatment. All of these parameters should be taken into account when a pharmacoeconomic evaluation is performed (either for administrative or scientific purposes) in order to ensure a comprehensive and reliable background for the evaluation in question. Treatment of acute leukaemia is expensive with a total cost of about $US3000 per patient per day during the induction. Although 80% of children with acute leukaemia are cured, only less than 50% of adults are cured. Thus, a great cost is associated with death during treatment and only optimal medical treatment with full-scale combination chemotherapy and full supportive treatment can keep the number of deaths to a minimum.Pharmacoeconomics, Leukaemia, Myeloid-leukaemia, Lymphoblastic-leukaemia, Cost-analysis, Quality-of-life, Antineoplastics, Reviews-on-treatment, Mortality

Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass

BACKGROUND: Altered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly via stimulation of GLP-1 secretion. We investigated the role of exogenous as well as endogenous BAs for GLP-1 secretion after RYGB by administering chenodeoxycholic acid (CDCA) and the BA sequestrant colesevelam (COL) both in the presence and the absence of a meal stimulus. METHODS: Two single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 2, or 4) no additions. RESULTS: In study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones. CONCLUSION: In RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB

Cladribine prolongs progression-free survival and time to second treatment compared to fludarabine and high-dose chlorambucil in chronic lymphocytic

We conducted a randomized phase III trial to compare the efficacy and safety of two purine analogs, cladribine and fludarabine, with high-dose chlorambucil, in patients with previously untreated chronic lymphocytic leukemia (CLL). Between 1997 and 2004, 223 patients with CLL were randomly assigned to cladribine, fludarabine or chlorambucil, for six cycles of therapy with frequent health-related quality of life assessments. There was no statistical difference for the primary endpoint of overall response with cladribine (70%), fludarabine (67%) and chlorambucil (59%), or complete remission (12%, 7% and 8%), respectively. However, the median progression-free survival (25, 10, 9 months) and median time to second treatment (40, 22, 21 months) were superior with cladribine. There was no significant difference in overall survival (96, 82 and 91 months), nor in toxicity or HRQoL assessments. Monotherapy with cladribine gives superior PFS and longer response duration than fludarabine and chlorambucil as first-line treatment of CLL