乳腺癌放疗＋哌柏西利或瑞波西利

　　哌柏西利或瑞波西利属于细胞有丝分裂周期蛋白依赖型激酶（CDK）4/6选择性抑制剂，已被证实可以显著提高激素受体阳性晚期乳腺癌内分泌治疗的效果。不过，哌柏西利或瑞波西利对于晚期乳腺癌同时放疗的安全性尚不明确。

　　2019年5月14日，欧洲乳腺癌专科医师学会《乳腺》在线发表意大利罗马生物医学大学的研究报告，探讨了激素受体阳性晚期乳腺癌患者放疗＋哌柏西利或瑞波西利的早期毒性反应。

　　该单中心回顾研究对2017年1月～2018年6月经组织学证实的乳腺癌远处或局部转移患者记录进行回顾分析，选择其中同时接受放疗＋哌柏西利或瑞波西利的患者，根据国家癌症研究所（NCI）不良事件通用术语标准4.0版（CTCAEV4.0）对毒性反应进行评定。

　　结果，连续16例晚期乳腺癌患者接受了共计24次放疗，其中：

• 13例患者（81.3%）接受了哌柏西利＋18次放疗

• 3例患者（18.7%）接受了瑞波西利＋5次放疗

　　大多数患者（68.7%）接受了对骨骼的姑息放疗（中位剂量30Gy，范围8～36Gy），5例患者（31.2%）接受了较高剂量（中位剂量50Gy，范围39.6-60Gy）针对孤立转移或孤立进展部位放疗。

　　血液毒性反应的发生率最高，其中2级、3级、4级中性粒细胞减少的发生率分别为12.5%、25%、6.3%；对于哌柏西利治疗前几轮已经出现中性粒细胞减少的患者，≥3级中性粒细胞减少的发生率高达60%。一例患者（6.3%）提前结束放疗（预计50Gy，实际48Gy），另一例患者（6.3%）暂停放疗2天。

　　结论，该研究结果表明，同时接受CDK4/6抑制剂和放疗可行，耐受性尚可；≥3级的血液毒性反应发生率高，但是大多数患者的治疗过程并未改变。应该仔细评估早期发生的CDK4/6抑制剂相关毒性反应，由于其通常将再次发生。推荐通过较高剂量有针对性放疗避开邻近健康组织。

Breast. 2019 May 14;46:70-74. [Epub ahead of print]

Concurrent radiotherapy with palbociclib or ribociclib for metastatic breast cancer patients: Preliminary assessment of toxicity.

Edy Ippolito, Carlo Greco, Sonia Silipigni, Emanuela Dell'Aquila, Gian Marco Petrianni, Giuseppe Tonini, Michele Fiore, Rolando Maria D'Angelillo, Sara Ramella.

Campus Bio-Medico University of Rome, Rome, Italy.

HIGHLIGHTS

• The concomitant treatment of CDK4/6 and radiotherapy is feasible.

• Hematological toxicity is common.

• High conformal radiotherapy treatment should be used to spare nearby healthy tissue.

• Previous CDK4/6 related toxicity should be carefully evaluated.

OBJECTIVE: To evaluate the early toxicity of concurrent use of radiotherapy in association with CDK4/6 inhibitors (palbociclib or ribociclib) in patients with hormone-receptors positive metastatic breast cancer.

MATERIAL AND METHODS: Records of patients with histologically proven metastatic or locally advanced breast cancer treated in our institution were reviewed. Patients who received radiotherapy and concurrent palbociclib or ribociclib were selected. Toxicity was assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0 (NCI-CTCAE V4.0).

RESULTS: Sixteen consecutive metastatic breast cancer patients with 24 radiotherapy treatments were studied. Thirteen patients (81.3%) received palbociclib, 3 (18.7%) patients received ribociclib concurrently with RT (18 and 5 radiotherapy courses respectively). The majority of patients (68.7%) received palliative radiotherapy to the bones (median dose 30Gy, range 8-36Gy). Five patients (31.2%) were treated in oligo-metastatic or oligo-progressive sites of disease with higher doses (median dose=50Gy, range 39.6-60Gy). The most common toxicity observed was hematological toxicity. Neutropenia was common (grade 2=12.5%; grade 3=25%, grade 4=6.3%); 60% of patients experiencing grade≥3 neutropenia had already experienced neutropenia during previous cycles of palbociclib. One patient (6.3%) completed the RT course earlier (48Gy of 50Gy prescribed) and another patient (6.3%) suspended RT for 2 days.

CONCLUSION: concomitant treatment of CDK4/6 and radiotherapy seems well tolerated; high grade hematological toxicity is common, but did not change treatment course in the majority of patients. Previous toxicity should be carefully evaluated as it usually reoccurs.

KEYWORDS: Palbociclib, Ribociclib, Radiotherapy, Toxicity

DOI: 10.1016/j.breast.2019.05.001