Moreau Philippe
Service d'Hématologie Clinique, CHU Hôtel-Dieu, Nantes.
Presse Med. 2006 Sep;35(9 Pt 2):1303-8. doi: 10.1016/s0755-4982(06)74809-6.
Thalidomide, administered orally, bortezomib (Velcade) intravenously and lenalidomide (Revlimid), also orally, are three agents that act on myeloma relapse. Thalidomide acts by a variety of mechanisms and is toxic to the peripheral nervous system as well as teratogenic. It acts in synergy with dexamethasone. Recent results prove that its use as first-line treatment combined with oral conventional "MP" chemotherapy improves survival in patients older than 65 years. Its use as first-line treatment with this chemotherapy appears likely. Bortezomib is the first drug in the proteasome inhibitor class. It too is toxic to the peripheral nervous system and synergistic with dexamethasone. Several studies show its efficacy as first-line 'induction treatment' with dexamethasone, in patients to receive a subsequent autologous stem cell transplantation. The combination of bortezomib and "MP" is also promising. Lenalidomide, a structural analog of thalidomide, is effective in relapsing patients. Its toxicity is essentially hematologic. It is also synergistic with dexamethasone and promising as first-line treatment. These different drugs can be used successively at relapse, making myeloma a chronic disease. They can also be used together for greater effectiveness. These combinations will replace conventional chemotherapies in the future.
口服沙利度胺、静脉注射硼替佐米(万珂)以及同样口服的来那度胺(瑞复美)是作用于骨髓瘤复发的三种药物。沙利度胺通过多种机制发挥作用,对周围神经系统有毒性且具有致畸性。它与地塞米松协同作用。近期结果证明,将其作为一线治疗与口服传统“MP”化疗联合使用可提高65岁以上患者的生存率。其作为这种化疗的一线治疗方法似乎可行。硼替佐米是蛋白酶体抑制剂类的第一种药物。它同样对周围神经系统有毒性且与地塞米松协同作用。多项研究表明,在接受后续自体干细胞移植的患者中,它作为与地塞米松联合的一线“诱导治疗”有效。硼替佐米与“MP”的联合使用也很有前景。来那度胺是沙利度胺的结构类似物,对复发患者有效。其毒性主要为血液学毒性。它也与地塞米松协同作用,作为一线治疗很有前景。这些不同的药物在复发时可相继使用,使骨髓瘤成为一种慢性病。它们也可联合使用以提高疗效。这些联合用药在未来将取代传统化疗。