177Lu-EDTMP与153Sm-EDTMP在等剂量基础上对疼痛性骨转移患者的临床疗效及安全性比较

Clinical Efficacy and Safety Comparison of 177Lu-EDTMP with 153Sm-EDTMP on an Equidose Basis in Patients with Painful Skeletal Metastases.

作者信息

Thapa Pradeep, Nikam Dilip, Das Tapas, Sonawane Geeta, Agarwal Jai Prakash, Basu Sandip

机构信息

Radiation Medicine Centre, Bhabha Atomic Research Centre, Tata Memorial Hospital Annexe, Mumbai, India.

Department of Radiation Oncology, Cama and Albless Hospital, Mumbai, India.

出版信息

J Nucl Med. 2015 Oct;56(10):1513-9. doi: 10.2967/jnumed.115.155762. Epub 2015 Aug 27.

DOI:10.2967/jnumed.115.155762

PMID:26315829

Abstract

UNLABELLED

This prospective study compared 177Lu-ethylene diamine tetramethylene phosphonate (EDTMP) with 153Sm-EDTMP for painful skeletal metastases.

METHODS

Half of the 32 patients were treated with 177Lu-EDTMP and half with 153Sm-EDTMP, at 37 MBq/kg of body weight. Analgesic, pain, and quality-of-life scores (EORTC, Karnofsky, ECOG) and bone proliferation marker were used to examine efficacy. Hematologic toxicity was evaluated using NCI-CTCAE and compared between groups at baseline and each month till 3 mo after therapy. Pain relief was categorized as complete, partial, minimal, or none.

RESULTS

Pain relief with 177Lu-EDTMP was 80%: 50% complete, 41.67% partial, and 8.33% minimal. Pain relief with 153Sm-EDTMP was 75%: 33.33% complete, 58.33% partial, and 8.33% minimal. The difference was not significant (P=1.000). Quality of life at 3 mo after therapy improved significantly in both groups as per ECOG score (P=0.014 and 0.005 for 177Lu-EDTMP and 153Sm-EDTMP, respectively), Karnofsky index (P=0.007 and 0.023 for 177Lu-EDTMP and 153Sm-EDTMP, respectively), and EORTC score (P=0.004 and <0.001 for 177Lu-EDTMP and 153Sm-EDTMP, respectively). Bone proliferation marker in responders of both groups dropped significantly (P=0.008 for 177Lu-EDTMP and P=0.019 for 153Sm-EDTMP), parallel to clinical response. For 177Lu-EDTMP, anemia, leukopenia, and thrombocytopenia were nonserious (grade I/II) in 46.67%, 46.67%, and 20%, respectively, and serious (grade III/IV) in 20%, 6.67%, and 0%, respectively. For 153Sm-EDTMP, anemia, leukopenia, and thrombocytopenia were nonserious (grade I/II) in 62.5%, 31.25%, and 18.75%, respectively, and serious (grade III/IV) in 18.75%, 0%, and 6.25%, respectively. One patient treated with 153Sm-EDTMP had grade IV thrombocytopenia but required no blood transfusion. Differences between groups were not significant for either nonserious or serious toxicity. For 177Lu-EDTMP, 3 of 12 responders experienced the flare phenomenon on the third day after therapy and one on the fifth day, showing no response to therapy. For 153Sm-EDTMP, 2 of 12 responders experienced the flare phenomenon, both on the third day after therapy.

CONCLUSION

177Lu-EDTMP has pain response efficacy similar to that of 153Sm-EDTMP and is a feasible and safe alternative, especially in centers with no nearby access to 153Sm-EDTMP.

摘要

未标注

本前瞻性研究比较了177Lu-乙二胺四亚甲基膦酸盐（EDTMP）与153Sm-EDTMP治疗疼痛性骨转移的效果。

方法

32例患者中，一半接受177Lu-EDTMP治疗，另一半接受153Sm-EDTMP治疗，剂量均为37MBq/kg体重。使用镇痛、疼痛和生活质量评分（欧洲癌症研究与治疗组织、卡诺夫斯基、美国东部肿瘤协作组）以及骨增殖标志物来评估疗效。采用美国国立癌症研究所常见不良反应事件评价标准（NCI-CTCAE）评估血液学毒性，并在基线时及治疗后直至3个月期间每月对两组进行比较。疼痛缓解分为完全缓解、部分缓解、轻微缓解或无缓解。

结果

177Lu-EDTMP的疼痛缓解率为80%：完全缓解50%，部分缓解41.67%，轻微缓解8.33%。153Sm-EDTMP的疼痛缓解率为75%：完全缓解33.33%，部分缓解58.33%，轻微缓解8.33%。差异无统计学意义（P = 1.000）。根据美国东部肿瘤协作组评分（177Lu-EDTMP和153Sm-EDTMP分别为P = 0.014和0.005）、卡诺夫斯基指数（177Lu-EDTMP和153Sm-EDTMP分别为P = 0.007和0.023）以及欧洲癌症研究与治疗组织评分（177Lu-EDTMP和153Sm-EDTMP分别为P = 0.004和<0.001），两组治疗后3个月的生活质量均显著改善。两组缓解者的骨增殖标志物均显著下降（177Lu-EDTMP为P = 0.008，153Sm-EDTMP为P = 0.019），与临床反应平行。对于177Lu-EDTMP，贫血、白细胞减少和血小板减少的非严重（I/II级）发生率分别为46.67%、46.67%和20%，严重（III/IV级）发生率分别为20%、6.67%和0%。对于153Sm-EDTMP，贫血、白细胞减少和血小板减少的非严重（I/II级）发生率分别为62.5%、31.25%和18.75%，严重（III/IV级）发生率分别为18.75%、0%和6.25%。1例接受153Sm-EDTMP治疗的患者出现IV级血小板减少，但无需输血。两组在非严重或严重毒性方面的差异均无统计学意义。对于177Lu-EDTMP，12例缓解者中有3例在治疗后第3天出现疼痛加剧现象，1例在第5天出现，对治疗无反应。对于153Sm-EDTMP，12例缓解者中有2例在治疗后第3天出现疼痛加剧现象。