Wilky Breelyn A, Loeb David M
Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Department of Pediatric Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland.
Clin Exp Pharmacol. 2013 Jun;3(3). doi: 10.4172/2161-1459.1000131.
Primary and metastatic malignant bone lesions result in significant pain and disability in oncology patients. Targeted bone-seeking radioisotopes including Samarium ethylene-diamine-tetramethylene-phosphonic acid (Sm-EDTMP) have been shown to effectively palliate bone pain, often when external beam radiotherapy (EBRT) is not feasible. However, recent evidence also suggests Sm-EDTMP has cytotoxic activity either alone or in combination with chemotherapy or EBRT. Sm-EDTMP may be useful as anti-neoplastic therapy apart from pain palliation in a variety of malignancies. For prostate cancer patients, several phase I and II clinical trials have shown that combined Sm-EDTMP and docetaxel-based chemotherapy can result in >50% decrease in prostate-specific antigen with manageable myelosuppression. In hematologic malignancies, Sm-EDTMP produced clinical responses when combined with bortezomib in multiple myeloma. Sm-EDTMP also can be used with myeloablative chemotherapy for marrow conditioning prior to stem cell transplant. In osteosarcoma, Sm-EDTMP infusion delivers radiation to multiple unresectable lesions simultaneously and provides local cytotoxicity without soft tissue damage that can be combined with chemotherapy or radiation. Prior to routine incorporation of Sm-EDTMP into therapeutic regimens, we must learn how to ensure optimal delivery to tumors, determine which patients are likely to benefit, improve our ability to assess clinical response in bone lesions and further evaluate the efficacy Sm-EDTMP in combination with chemotherapy, radiation and novel targeted agents.
原发性和转移性恶性骨病变会给肿瘤患者带来严重疼痛和功能障碍。包括钐乙二胺四亚甲基膦酸（Sm-EDTMP）在内的靶向亲骨性放射性同位素已被证明能有效缓解骨痛，通常在外照射放疗（EBRT）不可行时使用。然而，最近的证据还表明，Sm-EDTMP单独或与化疗或EBRT联合使用时具有细胞毒性活性。除了缓解多种恶性肿瘤的疼痛外，Sm-EDTMP还可能作为抗肿瘤治疗手段。对于前列腺癌患者，多项I期和II期临床试验表明，Sm-EDTMP与基于多西他赛的化疗联合使用可使前列腺特异性抗原降低>50%，且骨髓抑制可控。在血液系统恶性肿瘤中，Sm-EDTMP与硼替佐米联合用于多发性骨髓瘤时产生了临床反应。Sm-EDTMP还可与清髓性化疗联合用于干细胞移植前的骨髓预处理。在骨肉瘤中，Sm-EDTMP输注可同时向多个无法切除的病灶输送辐射，并提供局部细胞毒性，且不会造成软组织损伤，可与化疗或放疗联合使用。在将Sm-EDTMP常规纳入治疗方案之前，我们必须了解如何确保其最佳输送至肿瘤，确定哪些患者可能受益，提高我们评估骨病变临床反应的能力，并进一步评估Sm-EDTMP与化疗、放疗及新型靶向药物联合使用的疗效。
