Chowdhary Mudit, Sen Neilayan, Chowdhary Akansha, Usha Lydia, Cobleigh Melody A, Wang Dian, Patel Kirtesh R, Barry Parul N, Rao Ruta D
Department of Radiation Oncology, Rush University Medical Center, Chicago, Illinois.
Department of Medicine, Division of Hematology and Oncology, Northwestern University School of Medicine, Chicago, Illinois.
Adv Radiat Oncol. 2019 Apr 3;4(3):453-457. doi: 10.1016/j.adro.2019.03.011. eCollection 2019 Jul-Sep.
Palbociclib is a selective cyclin-dependent kinase 4/6 inhibitor approved for metastatic ER+/HER2- breast cancer. Preclinical evidence suggests a possible synergistic effect of palbociclib when combined with radiation therapy (RT); however, the toxicity of this pairing is unknown. We report preliminary results on the use of this combination.
Records of patients treated with palbociclib at our institution from 2015 to 2018 were retrospectively reviewed. Patients who received RT for symptomatic metastases concurrently or within 14 days of palbociclib were included. Local treatment effect was assessed by clinical examination and subsequent computed tomography/magnetic resonance imaging. Toxicity was graded based on Common Terminology Criteria for Adverse Events version 5.0.
A total of 16 women received palliative RT in close temporal proximity to palbociclib administration. Four patients received palbociclib before RT (25.0%), 5 concurrently (31.3%), and 7 after RT (43.8%). The median interval from closest palbociclib use to RT was 5 days (range, 0-14). The following sites were irradiated in decreasing order of frequency: bone (11 axial skeleton [9 vertebra and 2 other]; 4 pelvis; 3 extremity), brain (4: 3 whole brain RT and 1 stereotactic radiosurgery), and mediastinum (1). The median and mean follow-up time is 14.7 and 17.6 months (range, 1.7-38.2). Pain relief was achieved in all patients. No radiographic local failure was noted in the 13 patients with evaluable follow-up imaging. Leukopenia, neutropenia, and thrombocytopenia were seen in 4 (25.0%), 5 (31.3%), and 1 (6.3%) patient before RT. After RT, 5 (31.3%), 1 (6.3%), and 3 (18.8%) patients were leukopenic, neutropenic, and thrombocytopenic, respectively. All but 2 (grade 2) hematologic toxicities were grade 1. No acute or late grade 2+ cutaneous, neurologic, or gastrointestinal toxicities were noted. Toxicity results did not differ based on disease site, palbociclib-RT temporal association, or irradiated site.
The use of RT in patients receiving palbociclib resulted in minimal grade 2 and no grade 3+ toxicities. This preliminary work suggests that symptomatic patients receiving palbociclib may be safely irradiated.
帕博西尼是一种选择性细胞周期蛋白依赖性激酶4/6抑制剂，已被批准用于治疗转移性雌激素受体阳性/人表皮生长因子受体2阴性（ER+/HER2-）乳腺癌。临床前证据表明，帕博西尼与放射治疗（RT）联合使用可能具有协同作用；然而，这种联合治疗的毒性尚不清楚。我们报告了使用这种联合治疗的初步结果。
回顾性分析了2015年至2018年在我院接受帕博西尼治疗的患者记录。纳入在帕博西尼治疗期间或治疗后14天内因有症状的转移灶接受放疗的患者。通过临床检查及随后的计算机断层扫描/磁共振成像评估局部治疗效果。根据不良事件通用术语标准第5.0版对毒性进行分级。
共有16名女性在接受帕博西尼治疗的同时或临近治疗时接受了姑息性放疗。4例患者在放疗前接受帕博西尼治疗（25.0%），5例同时接受（31.3%），7例在放疗后接受（43.8%）。从最近一次使用帕博西尼到放疗的中位间隔时间为5天（范围0 - 14天）。放疗部位按频率递减顺序为：骨（11例为轴向骨骼[9例为椎体，2例为其他部位]；4例为骨盆；3例为四肢）、脑（4例：3例为全脑放疗，1例为立体定向放射外科手术）和纵隔（1例）。中位随访时间和平均随访时间分别为14.7个月和17.6个月（范围1.7 - 38.2个月）。所有患者均实现了疼痛缓解。在13例有可评估随访影像的患者中，未发现影像学局部复发。放疗前，4例（25.0%）、5例（31.3%）和1例（6.3%）患者出现白细胞减少、中性粒细胞减少和血小板减少。放疗后，分别有5例（31.3%）、1例（6.3%）和3例（18.8%）患者出现白细胞减少、中性粒细胞减少和血小板减少。除2例（2级）血液学毒性外，其余均为1级。未发现急性或晚期2级及以上的皮肤、神经或胃肠道毒性。毒性结果在疾病部位、帕博西尼与放疗的时间关联或放疗部位方面无差异。
接受帕博西尼治疗的患者使用放疗导致2级毒性最小，且无3级及以上毒性。这项初步研究表明，接受帕博西尼治疗的有症状患者可安全地接受放疗。
