Harvard Medical School, Boston, Massachusetts.
Division of Dermatology, University of California, Los Angeles Medical Center, Santa Monica.
JAMA Dermatol. 2020 Oct 1;156(10):1079-1085. doi: 10.1001/jamadermatol.2020.1795.
Up to 90% of patients treated with an epidermal growth factor receptor inhibitor (EGFRi) experience cutaneous toxic effects that are negatively associated with quality of life and lead to treatment interruptions. The Skin Toxicity Evaluation Protocol With Panitumumab trial found reduced incidence of skin toxicity and quality of life impairment with preemptive use of doxycycline hyclate, topical corticosteroids, moisturizers, and sunscreen, demonstrating the benefit of prophylactic treatment for skin toxicity.
To evaluate the association of a comprehensive skin toxicity program with adherence to prophylaxis guidelines for the prevention of EGFRi-associated cutaneous toxic effects.
DESIGN, SETTING, AND PARTICIPANTS: A retrospective cohort study was conducted of all adult patients receiving at least 1 dose of cetuximab at the Dana-Farber Cancer Institute in the calendar year 2012 (2 years after publication of the Skin Toxicity Evaluation Protocol With Panitumumab) or the calendar year 2017 (2 years after full implementation of the Skin Toxicities from Anticancer Therapies program).
Primary outcomes were rate of preemptive rash treatment and selection of preemptive agents. Secondary outcomes were incidence of rash, rates of rescue treatments, rates of cetuximab dose changes or interruptions, and overall survival at 2 years.
There were 118 patients (85 men; median age, 62.4 years [range, 23.5-91.7 years]) treated with cetuximab in 2012 and 90 patients (70 men; median age, 62.5 years [range, 30.7-90.5 years]) treated with cetuximab in 2017; 11 patients (9%) in 2012 and 31 patients (34%) in 2017 were treated at Dana-Farber Cancer Institute affiliate sites. At cetuximab treatment initiation, 29 patients (25%) in 2012 and 42 patients (47%) in 2017 were prophylactically treated for skin toxicity (P < .001). From 2012 to 2017, preemptive tetracycline use (13 of 29 [45%] to 30 of 42 [71%]; P = .02) and topical corticosteroid use (2 of 29 [7%] to 24 of 42 [57%]; P < .001) increased and topical antibiotic use (23 of 29 [79%] to 18 of 42 [43%]; P = .002) decreased. There was no significant difference in incidence of rash by prophylaxis status. Patients prescribed prophylactic treatment were 94% less likely to require a first rescue treatment for rash (adjusted odds ratio, 0.06; 95% CI, 0.02-0.16; P < .001), 74% less likely to require a second rescue treatment for rash (adjusted odds ratio, 0.26; 95% CI, 0.08-0.83; P = .02), and 79% less likely to experience a cetuximab dose change or interruption (adjusted odds ratio, 0.21; 95% CI, 0.06-0.81; P = .02) than patients not prescribed prophylactic treatment, adjusting for treatment site and year.
Dermatologists can add value to oncology care by raising awareness of appropriate treatment options and increasing adherence to evidence-based prophylaxis protocols for EGFRi-associated rash, which is associated with decreased interventions and toxicity-associated chemotherapy interruptions.
多达 90%接受表皮生长因子受体抑制剂 (EGFRi) 治疗的患者会出现皮肤毒性反应,这些反应与生活质量呈负相关,并导致治疗中断。皮肤毒性评估协议与帕尼单抗试验发现,预防性使用盐酸多西环素、局部皮质类固醇、保湿剂和防晒霜可降低皮肤毒性和生活质量损害的发生率,证明了预防治疗皮肤毒性的益处。
评估综合皮肤毒性方案与预防表皮生长因子受体抑制剂相关皮肤毒性反应的预防指南的一致性。
设计、设置和参与者:对 2012 年(发布皮肤毒性评估协议与帕尼单抗后 2 年)或 2017 年(全面实施皮肤毒性治疗方案后 2 年)在达纳-法伯癌症研究所接受至少 1 剂西妥昔单抗治疗的所有成年患者进行回顾性队列研究。
主要结局是预防性皮疹治疗的发生率和预防性药物的选择。次要结局是皮疹的发生率、皮疹的抢救治疗率、西妥昔单抗剂量改变或中断率以及 2 年的总生存率。
2012 年接受西妥昔单抗治疗的患者有 118 例(85 例男性;中位年龄 62.4 岁[范围,23.5-91.7 岁]),2017 年接受西妥昔单抗治疗的患者有 90 例(70 例男性;中位年龄 62.5 岁[范围,30.7-90.5 岁]);2012 年 11 例(9%)和 2017 年 31 例(34%)患者在达纳-法伯癌症研究所的附属机构接受治疗。在开始西妥昔单抗治疗时,2012 年有 29 例(25%)和 2017 年有 42 例(47%)患者预防性治疗皮肤毒性(P < .001)。2012 年至 2017 年,预防性使用四环素(13 例[45%]至 30 例[71%];P = .02)和局部皮质类固醇(2 例[7%]至 24 例[57%];P < .001)的使用率增加,而局部抗生素(23 例[79%]至 18 例[43%];P = .002)的使用率降低。预防性治疗与皮疹发生率无显著相关性。接受预防性治疗的患者首次因皮疹需要抢救治疗的可能性降低 94%(调整后的优势比,0.06;95%CI,0.02-0.16;P < .001),因皮疹需要第二次抢救治疗的可能性降低 74%(调整后的优势比,0.26;95%CI,0.08-0.83;P = .02),需要改变西妥昔单抗剂量或中断治疗的可能性降低 79%(调整后的优势比,0.21;95%CI,0.06-0.81;P = .02),与未接受预防性治疗的患者相比,调整治疗部位和年份后。
皮肤科医生可以通过提高对适当治疗选择的认识并增加对表皮生长因子受体抑制剂相关皮疹的循证预防方案的依从性,为肿瘤学护理增加价值,这与减少干预和与毒性相关的化疗中断有关。