多发性骨髓瘤
医学
多重耐药
药理学
临床试验
药品
抗药性
药代动力学
P-糖蛋白
维拉帕米
化疗
白血病
内科学
肿瘤科
免疫学
生物
钙
微生物学
作者
P Sonneveld,H M Lokhorst,Paula J.M. Vossebeld
出处
期刊:PubMed
日期:1997-10-01
卷期号:34 (4 Suppl 5): 34-9
被引量:223
摘要
The development of multidrug resistance (MDR) is a major obstacle to improving treatment outcomes in multiple myeloma. Recent studies have indicated that several specific mechanisms of MDR may be involved in clinically refractory multiple myeloma patients, such as expression of P-glycoprotein (P-gp), expression of the lung-resistance protein (LRP) and suppression of apoptosis via expression of Bcl-2. The emergence of these mechanisms of MDR in multiple myeloma is enhanced by exposure to chemotherapeutic agents. Recently, clinical reversal of MDR by noncytotoxic P-gp modulators such as verapamil, cyclosporin A (CsA), and PSC 833 was explored in acute leukemia and multiple myeloma. Preliminary results from clinical phase I/II trials indicate that reversal of MDR via modulation of P-gp is possible and that coadministration of these MDR modulators with chemotherapeutic agents alters the plasma pharmacokinetics of chemotherapeutic agents. Phase II and III clinical trials investigating the efficacy of these and other agents in the reversal of MDR in hematologic malignancies are ongoing.
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