Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature.
Enhanced toxicity with CDK 4/6 inhibitors and palliative radiotherapy: Non-consecutive case series and review of the literature.
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DOI：
10.1016/j.tranon.2020.100939
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发表时间：
2021-01
影响因子：
5
通讯作者：
White M
中科院分区：
文献类型：
--
作者：
David S;Ho G;Day D;Harris M;Tan J;Goel S;Hanna GG;Srivastava R;Kruss G;McDowell L;White M
CDK 4/6 抑制剂常用于晚期激素受体阳性乳腺癌患者。许多患者在接受 CDK 4/6 抑制剂治疗的同时，接受针对症状性疾病的姑息性放疗。关于 CDK 4/6 抑制剂与姑息性放射治疗相结合的安全性的数据很少。我们报告了我们机构的 5 例病例，在使用 CDK 4/6 抑制剂治疗期间或之前进行放疗时，观察到放疗毒性增强。我们回顾了临床前和机制数据，并假设了这种现象的可能机制。目前，大多数转移性激素受体阳性、HER-2 阴性乳腺癌患者的一线全身治疗是芳香酶抑制剂与细胞周期蛋白依赖性激酶 (CDK) 4/6 抑制剂的联合治疗。通常，这些患者需要姑息性放射治疗 (RT) 来治疗症状疾病。关于 CDK 4/6 抑制剂与姑息性 RT 联合使用的安全性的数据很少，文献中的病例报告相互矛盾。我们报告了我们机构的 5 例病例，在使用 CDK 4/6 抑制剂治疗期间或之前给予姑息剂量的放疗时，观察到放疗毒性增强。在回顾临床前和机制数据后，我们假设 CDK4/6 抑制对正常组织和肿瘤微环境的影响可能会阻碍组织恢复并加剧急性放射和放射回忆毒性。需要进一步的研究来阐明这种组合的潜在毒性。临床医生应考虑将 CDK 4/6 抑制剂与姑息性放疗联合使用时的潜在风险，并相应地对患者进行个体化管理。
CDK 4/6 inhibitors are commonly used in patients with advanced hormone receptor positive breast cancer. Many patients receive palliative radiotherapy for symptomatic disease concomitantly with a CDK 4/6 inhibitor. There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative radiotherapy. We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when RT was delivered during or prior to treatment with a CDK 4/6 inhibitor. We review pre-clinical and mechanistic data and hypothesise on possible mechanisms for this phenomenon. Current first-line systemic treatment in most patients with metastatic hormone receptor-positive, HER-2 negative breast cancer is an aromatase inhibitor in combination with a cyclin dependant kinase (CDK) 4/6 inhibitor. Frequently, these patients require palliative radiotherapy (RT) for symptomatic disease management. There is a paucity of data on the safety of combining a CDK 4/6 inhibitor with palliative RT, with conflicting case reports in the literature. We report on 5 cases at our institution where enhanced radiotherapy toxicity was observed when palliative doses of RT was delivered during or prior to treatment with a CDK 4/6 inhibitor. After review of pre-clinical and mechanistic data, we hypothesise that the effects of CDK4/6 inhibition on normal tissue and the tumour microenvironment may impede tissue recovery and exacerbate acute radiation and radiation recall toxicities. Further studies are required to clarify the potential toxicities of this combination. Clinicians should consider the potential risks when combining CDK 4/6 inhibitors with palliative RT and individualise patient management accordingly.
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影响因子：
2.3
作者：
Chowdhary, Mudit;Sen, Neilayan;Rao, Ruta D.
通讯作者：
Rao, Ruta D.
影响因子：
3.9
作者：
Meattini, Icro;Desideri, Isacco;Livi, Lorenzo
通讯作者：
Livi, Lorenzo
影响因子：
7
作者：
Whittaker S;Madani D;Joshi S;Chung SA;Johns T;Day B;Khasraw M;McDonald KL
通讯作者：
McDonald KL
影响因子：
8
作者：
通讯作者：
--
DOI：
10.1634/theoncologist.2009-0090
发表时间：
2010
期刊：
The oncologist
影响因子：
--
作者：
Burris HA 3rd;Hurtig J
通讯作者：
Hurtig J