1.Comparative Cost-Effectiveness of Drugs in Early versus Late Stages of Cancer; Review of the Literature and a Case Study in Breast Cancer.
Dvortsin E1, Gout-Zwart J1, Eijssen EL1, van Brussel J1, Postma MJ1,2. PLoS One. 2016 Jan 22;11(1):e0146551. doi: 10.1371/journal.pone.0146551. eCollection 2016.
BACKGROUND: Many oncological drugs that are being used in the adjuvant setting were first submitted for reimbursement in the metastatic stage, with differences in incremental cost-effectiveness ratios (ICERs) in both settings having potential implications for reimbursement and pricing. The aim of this study is to identify a possible trend in the cost-effectiveness for the early/adjuvant and late/metastatic stages of oncological drugs through review and case study.
2.The Role of New Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia.
Pophali PA1, Patnaik MM. Cancer J. 2016 Jan-Feb;22(1):40-50. doi: 10.1097/PPO.0000000000000165.
Imatinib mesylate was the first tyrosine kinase inhibitor (TKI) approved for the management of chronic myeloid leukemia. Imatinib produces acceptable responses in approximately 60% of patients, with approximately 20% discontinuing therapy because of intolerance and approximately 20% developing drug resistance. The advent of newer TKIs, such as nilotinib, dasatinib, bosutinib, and ponatinib, has provided multiple options for patients. These agents are more potent, have unique adverse effect profiles, and are more likely to achieve relevant milestones, such as early molecular responses (3-6 months) and optimal molecular responses (12 months). The acquisition of BCR-ABL kinase domain mutations is also reportedly lower with these drugs. Thus far, none of the randomized phase III clinical trials have shown a clinically significant survival difference between frontline imatinib versus newer TKIs. Cost and safety issues with the newer TKIs, such as vascular disease with nilotinib and ponatinib and pulmonary hypertension with dasatinib, have dampened the enthusiasm of using these drugs as frontline options.
3.Structure-Activity Relationship Study of Rakicidins: Overcoming Chronic Myeloid Leukemia Resistance to Imatinib with 4-Methylester-Rakicidin A.
Sang F1,2, Ding Y1, Wang J1, Sun B1, Sun J1, Geng Y1,3, Zhang Z4, Ding K4, Wu LL1,3, Liu JW1, Bai C3, Yang G1, Zhang Q1, Li LY1, Chen Y1. J Med Chem. 2016 Feb 11;59(3):1184-96. doi: 10.1021/acs.jmedchem.5b01841. Epub 2016 Jan 27.
Natural product rakicidin A induces cell death in TKI-resistant chronic myelogenous leukemia (CML) cells. Therefore, 14 rakicidin A analogues were synthesized via a highly efficient combinatorial strategy and were evaluated against CML cell lines. The conjugated diene moiety was found to be crucial for the anti-CML activity of rakicidin A, and the changes in the configuration(s) at C-2, C-3, C-14, C-15, and C-16 resulted in lower levels of anti-CML activity. The most promising compound was 4-methylester rakicidin A (1a). Compared with rakicidin A, 1a exhibited 2.8-fold greater potency against the imatinib-resistant cell line K562/G(+) and approximately 100-fold enhanced potency compared with that of imatinib. Furthermore, compound 1a demonstrated a significantly lower resistance index against Ba/F3 cells expressing BCR-ABL(T315I) than bosutinib, dasatinib, nilotinib, and ponatinib, while 1a exhibited less effect on normal hematopoietic cells.
4.Health-related quality of life during bosutinib (SKI-606) therapy in patients with advanced chronic myeloid leukemia after imatinib failure.
Whiteley J1, Reisman A1, Shapiro M2, Cortes JE3, Cella D4. Curr Med Res Opin. 2016 Apr 5:1-40. [Epub ahead of print]
OBJECTIVES: The tyrosine kinase inhibitor bosutinib has demonstrated activity in patients with advanced phase chronic myeloid leukemia (CML), but effects on health-related quality of life (HRQoL) remain unexplored. This study evaluated HRQoL in advanced CML patients receiving bosutinib in an ongoing phase 2 study following resistance or intolerance to prior imatinib therapy.
