Ueno Naoto T, de Souza Jonas A, Booser Daniel, Nakayama Kazutaka, Madewell John, Wendt Richard E, Hortobagyi Gabriel N, Podoloff Donald, Champlin Richard E
Department of Breast Medical Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Clin Breast Cancer. 2009 Aug;9(3):173-7. doi: 10.3816/CBC.2009.n.028.
Bone-targeted radiation therapy is an attractive strategy for addressing bone disease with minimal systemic toxicity. This pilot study was designed to determine the safety and efficacy of (166)Holmium (Ho)-DOTMP for irradiating malignant cells and adjacent marrow in women with bone-only metastatic breast cancer.
Subjects included 6 women aged < or = 65 years with breast cancer and bone-only metastases at M. D. Anderson Cancer Center. The activity of (166)Ho-DOTMP was calculated to deliver a therapeutic absorbed dose of 22 Gy (n = 3) or 28 Gy (n = 3) to the marrow. Treatment was followed by autologous stem cell transplantation to circumvent the anticipated myelosuppresion. Median follow-up time was 40 months.
All subjects showed prompt hematologic recovery. No patient experienced grade 3/4 acute toxicity aside from myelosuppression. Two patients developed hemorrhagic cystitis 2 years after therapy. One patient developed myelodysplastic syndrome but was found to have had pre-existing trisomy 8. Two patients remained progression free without evidence of disease for more than 6 years. Five women experienced disease relapse (4 at extraosseous sites) and died of progressive disease. Median time to progression was 10.4 months.
The approach of bone-targeted radiation therapy with (166)Ho-DOTMP had an acceptable toxicity profile, and sustained complete response was obtained in 2 of 6 patients. We are conducting a phase II study to evaluate the efficacy of targeted skeletal radiation therapy for treating bone-only metastases.
骨靶向放射治疗是一种极具吸引力的策略，可用于治疗骨疾病且全身毒性极小。本初步研究旨在确定钬-166（166Ho）-二膦酸甲基亚丙基三胺五甲叉膦酸（DOTMP）对仅发生骨转移的乳腺癌女性患者的恶性细胞及邻近骨髓进行照射的安全性和有效性。
研究对象包括6名年龄小于或等于65岁、在MD安德森癌症中心患有乳腺癌且仅发生骨转移的女性。计算得出166Ho-DOTMP的活度可向骨髓提供22戈瑞（n = 3）或28戈瑞（n = 3）的治疗吸收剂量。治疗后进行自体干细胞移植以规避预期的骨髓抑制。中位随访时间为40个月。
所有受试者均迅速出现血液学恢复。除骨髓抑制外，无患者经历3/4级急性毒性反应。两名患者在治疗后2年出现出血性膀胱炎。一名患者发生骨髓增生异常综合征，但发现其先前存在8号染色体三体。两名患者无疾病进展，无疾病证据超过6年。五名女性出现疾病复发（4例发生在骨外部位）并死于疾病进展。中位进展时间为10.4个月。
采用166Ho-DOTMP进行骨靶向放射治疗的方法具有可接受的毒性特征，6例患者中有2例获得持续完全缓解。我们正在进行一项II期研究，以评估靶向骨骼放射治疗对仅发生骨转移的疗效。
