The clinical effectiveness agency for England and Wales says that it now favors the use of thalidomide and bortezomib as options for the first-line treatment of multiple myeloma.
In draft guidance issued June 2, the National Institute for Health and Clinical Effectiveness recommended that oral thalidomide, in combination with an alkylating agent and a corticosteroid, should be a treatment option for people who are not, because of age or comorbidities, eligible for high-dose chemotherapy with stem cell transplantation.
The NICE reviewers estimated that a large portion of U.K. patients with multiple myeloma fall into this category, as the vast majority are older than 75.
A second drug, bortezomib, was also recommended by NICE for the same group of patients with multiple myeloma, also in combination with an alkylating agent and a corticosteroid, but only for people unable to tolerate or who have contraindications to thalidomide, usually clotting or renal disorders. In 2006, NICE had refused to recommend bortezomib as first-line treatment for multiple myeloma over concerns about its cost; the following year it recommended the drug for the treatment of relapsed multiple myeloma.
Thalidomide and bortezomib work differently. The former is an immunomodulatory agent believed to have anti-inflammatory properties and also to inhibit tumor necrosis growth factor–alpha, though its exact mechanisms are not yet fully understood.
Developed in Germany in the 1950s and marketed in the United Kingdom as a sedative and morning sickness drug for pregnant women, thalidomide was withdrawn after it was shown to cause serious birth defects, but by the mid-1960s its anticancer properties were starting to be explored. In 2008, the European Medicines Agency recommended marketing approval for thalidomide for use in treating patients with multiple myeloma; thalidomide regimens were by then standard therapies for multiple myeloma in the United States, New Zealand, and Australia.
The cost for a 28-capsule pack of 50-mg thalidomide capsules is £298.48, and the recommended treatment dose is 200 mg per day for a maximum of 12 6-week cycles. Thalidomide is prescribed and dispensed in the United Kingdom under a scheme designed to eliminate the possibility of pregnancy in any woman who is taking the drug, or who is the partner of a man taking it.
Bortezomib is an anticancer drug that works by reducing tumor growth and was developed specifically for use in treating multiple myeloma. The drug is administered intravenously with a starting dose of 1.3 mg/m2 body surface area twice weekly for 2 weeks followed by a 10-day rest period, for a treatment cycle of 3 weeks. The treatment recommendation for responding patients is eight cycles; a 3.5-mg vial of bortezomib costs £762.38.
NICE originally rejected bortezomib as a first-line treatment for multiple myeloma because of cost, which is greater than that of thalidomide. Though the efficacy of the two drugs has never been compared head to head in a single randomized controlled trial, the NICE reviewers said evidence presented from other randomized controlled trials comparing thalidomide and bortezomib regimens with other chemotherapy regimens showed the two to be comparable in terms of prolonging progression-free and overall survival.
The reviewers estimated that since 75% of U.K .patients with multiple myeloma would be eligible for treatment with a thalidomide regimen, the inclusion of bortezomib as a secondary treatment option would not put an undue financial burden on the National Health Service.
Final guidance on both drugs is expected in July.
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英格兰和威尔士临床疗效评价机构表示，其目前主张选用沙立度胺和硼替佐米用于多发性骨髓瘤的一线治疗。
在6月2日发布的指南草案中，英国国家卫生与临床优化研究所(NICE)建议，对于因年龄或合并症而不适合接受高剂量化疗和干细胞移植的患者，应选用口服沙立度胺联合烷化剂和糖皮质激素进行治疗。
NICE评审人员表示，英国绝大多数多发性骨髓瘤患者的年龄为75岁以上，因此估计有很大比例属于上述这类患者。
第二种药物硼替佐米也被NICE推荐用于治疗相同的多发性骨髓瘤患者，也是与烷化剂和糖皮质激素联合使用，但仅针对不能耐受沙立度胺或存在沙立度胺禁忌证(通常为凝血或肾功能障碍)的患者。2006年，NICE因担心费用问题而拒绝推荐硼替佐米用于多发性骨髓瘤的一线治疗；2007年，其推荐该药用于治疗复发性多发性骨髓瘤。
沙立度胺和硼替佐米的作用机制各异。前者是一种被认为既具有抗炎作用又可抑制肿瘤坏死生长因子α的免疫调节剂，尽管其确切机制尚不完全清楚。
沙立度胺于20世纪50年代在德国研发成功，并作为孕妇用镇静和抗早孕反应药在英国上市，但因发现可导致严重出生缺陷而被撤市。不过，到了20世纪60年代中期，研究者开始着手研究其抗癌作用。2008年，欧洲药品管理局建议批准沙立度胺上市用于治疗多发性骨髓瘤；沙立度胺当时是美国、新西兰和澳大利亚的多发性骨髓瘤标准治疗药物。
一板28粒50mg沙立度胺胶囊的费用为298.48英镑，推荐治疗剂量为200 mg/d，6周为一个治疗周期，最多治疗12个周期。英国制订了一项旨在避免正在服用沙立度胺的女性或服用该药男性的女性伴侣怀孕的计划，该药的开具和配发均遵循该计划进行。
硼替佐米是一种通过抑制肿瘤生长而发挥作用的抗癌药，是为了治疗多发性骨髓瘤而专门研发。该药通过静脉给药，初始剂量为1.3 mg/m2体表面积，2次/w，连续2周，继以10天休息期，3周为1个治疗周期。 对有效患者的治疗建议是8个周期；一瓶3.5mg硼替佐米的费用为762.38英镑。
NICE最初反对将硼替佐米作为多发性骨髓瘤的一线治疗药物，因为其费用高于沙立度胺。尽管尚未在单个随机对照试验中对这两种药物的疗效进行直接“头对头”比较，但NICE评审人员表示，其他随机对照试验对沙立度胺和硼替佐米方案与其他化疗方案进行比较发现，这两种药物在延长无进展生存时间和总体生存时间方面具有可比性。
评审人员估计，鉴于75%的英国多发性骨髓瘤患者适合接受沙立度胺治疗，因此将硼替佐米作为二线治疗选择不会对英国国民医疗保健系统造成过多经济负担。
有关这两种药物的最终指南预计将在7月份完成。
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