Ghobrial Irene M, Rajkumar S Vincent
Division of Hematology, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA.
J Support Oncol. 2003 Sep-Oct;1(3):194-205.
Thalidomide has re-emerged as a novel antineoplastic agent with immunomodulatory and antiangiogenic activities. In the early sixties, it was withdrawn from the market after its infamous association with congenital abnormalities that left about 10,000 children affected world-wide. With strict regulations and precautions, thalidomide is now approved by the FDA for the treatment of erythema nodosum leprosum. Its role in cancer therapy is promising, with clinical trials in the past 5 years showing significant activity in multiple myeloma. Several trials are ongoing in other malignancies, such as myelodysplastic syndrome, agnogenic myeloid metaplasia, renal cell carcinoma, and prostate cancer. The major toxicities of thalidomide are birth defects, sensorimotor peripheral neuropathy, somnolence, rash, fatigue, and constipation. Less common side effects include deep venous thrombosis, Stevens-Johnson syndrome, elevated liver enzymes, malaise, and peripheral edema. The incidence and severity of adverse events are related to dose and duration of therapy. Doses of the drug of 200 mg/day or less are usually well tolerated. In this review, we will discuss the incidence and management of the side effects of thalidomide and the precautions and interventions needed to minimize the toxicities of this drug.
沙利度胺已重新成为一种具有免疫调节和抗血管生成活性的新型抗肿瘤药物。在20世纪60年代初,它因与先天性异常存在臭名昭著的关联而被撤出市场,全球约10000名儿童受其影响。在严格的监管和预防措施下,沙利度胺现已获美国食品药品监督管理局(FDA)批准用于治疗结节性红斑狼疮。其在癌症治疗中的作用前景广阔,过去5年的临床试验表明它在多发性骨髓瘤中具有显著活性。其他恶性肿瘤,如骨髓增生异常综合征、特发性骨髓化生、肾细胞癌和前列腺癌的多项试验正在进行中。沙利度胺的主要毒性包括出生缺陷、感觉运动性周围神经病变、嗜睡、皮疹、疲劳和便秘。较不常见的副作用包括深静脉血栓形成、史蒂文斯-约翰逊综合征、肝酶升高、不适和外周水肿。不良事件的发生率和严重程度与治疗剂量和疗程有关。该药物每日剂量200毫克或更低通常耐受性良好。在本综述中,我们将讨论沙利度胺副作用的发生率及管理,以及将该药物毒性降至最低所需的预防措施和干预措施。