Myeloma Division, John Theurer Cancer Center at Hackensack UMC, Hackensack, NJ 07601, USA.
Clin Lymphoma Myeloma Leuk. 2012 Jun;12(3):186-90. doi: 10.1016/j.clml.2012.01.004. Epub 2012 Feb 28.
Thalidomide and lenalidomide, in combination with dexamethasone, provide response rates ranging from 63%-79% after 4 cycles of therapy. Because of toxicities such as neuropathy and myelosuppression for thalidomide and lenalidomide, respectively, dose escalation has not been pursued. We evaluated a syncopated regimen of alternating weeks of thalidomide and lenalidomide to determine if a modified schedule allows for fewer dose reductions and, subsequently, superior efficacy. Although well tolerated, this phase II trial did not show superior efficacy compared with conventional dosing and scheduling of these agents.
Over the past decade, the novel agents thalidomide, lenalidomide, and bortezomib have emerged as effective treatment in patients with multiple myeloma (MM). Initially used in the relapse setting, these agents have been incorporated into frontline treatment algorithms. They have been combined in doublets with corticosteroids, in triplets with alkylators, or with each other. Because thalidomide and lenalidomide have different clinical activity and toxicity profiles, we designed a trial to evaluate a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone in patients with newly diagnosed MM to determine response and toxicity.
Twenty-two patients with newly diagnosed MM were treated with syncopated thalidomide (200 mg on days 1-7 and 15-21), lenalidomide (25 mg on days 8-14 and 22-28 for the first cycle and 50 mg on the same schedule for subsequent cycles) with weekly dexamethasone (40 mg). Each cycle lasted 28 days. MM parameters were assessed at the end of each cycle. It was intended that the patients proceed to stem cell mobilization and autologous transplantation after 4 cycles of therapy.
The median number of cycles administered was 3.5. The overall response was 68%. The regimen was well tolerated by the majority of the patients; only patient discontinued treatment because of toxicity.
We conclude that a syncopated schedule of thalidomide and lenalidomide with weekly dexamethasone was tolerated well, with no unexpected toxicities. However the response rate, even using lenalidomide at 50 mg, was not superior to standard dosing of thalidomide or lenalidomide plus dexamethasone.
沙利度胺和来那度胺与地塞米松联合使用，在 4 个疗程的治疗后，反应率在 63%至 79%之间。由于沙利度胺和来那度胺分别具有神经病变和骨髓抑制等毒性，因此没有进行剂量升级。我们评估了沙利度胺和来那度胺交替使用的交错方案，以确定是否修改方案可以减少剂量减少，并随后获得更好的疗效。尽管耐受良好，但与这些药物的常规剂量和方案相比，这项 2 期试验并未显示出更好的疗效。
在过去的十年中，新型药物沙利度胺、来那度胺和硼替佐米已成为多发性骨髓瘤（MM）患者的有效治疗方法。这些药物最初用于复发患者，现已被纳入一线治疗方案。它们与皮质类固醇联合用于双药治疗，与烷化剂联合用于三药治疗，或相互联合使用。由于沙利度胺和来那度胺具有不同的临床活性和毒性特征，我们设计了一项试验，以评估沙利度胺和来那度胺与每周地塞米松联合使用的交错方案在新诊断的 MM 患者中的疗效和毒性。
22 例新诊断的 MM 患者接受了同步治疗，方案为沙利度胺（第 1-7 天和第 15-21 天，每天 200mg）、来那度胺（第 1 周期每天 8-14 天和第 22-28 天，25mg，随后周期每天 50mg），同时每周给予地塞米松（40mg）。每个周期持续 28 天。在每个周期结束时评估 MM 参数。计划在 4 个周期的治疗后让患者进行干细胞动员和自体移植。
中位治疗周期数为 3.5 个。总体反应率为 68%。大多数患者对该方案耐受良好，只有 1 例患者因毒性而停止治疗。
我们得出结论，沙利度胺和来那度胺与每周地塞米松联合使用的交错方案耐受性良好，无意外毒性。然而，即使使用来那度胺 50mg，反应率也不比沙利度胺或来那度胺联合地塞米松的标准剂量优越。
