Lacouture M E, Laabs S M, Koehler M, Sweetman R W, Preston A J, Di Leo A, Gomez H L, Salazar V M, Byrne J A, Koch K M, Blackwell K L
Department of Dermatology, Northwestern University, 676 North St. Claire Street, Suite 1600, Chicago, IL 60611-2941, USA.
Breast Cancer Res Treat. 2009 Apr;114(3):485-93. doi: 10.1007/s10549-008-0020-7. Epub 2008 Jul 4.
Dermatologic events (DEs) in patients with cancer treated with lapatinib, a small-molecule dual tyrosine kinase inhibitor (TKI) of epidermal growth factor receptor (EGFR [ErbB1]) and HER2 (ErbB2), were characterized.
Nine clinical trials of metastatic cancer were included in this analysis. Lapatinib was administered at doses ranging from 1000 to 1500 mg/day as monotherapy (n=928) or in combination with paclitaxel or capecitabine (n=491). Patients not treated with lapatinib comprised the control group. Dermatologic events included hand-foot syndrome, rash, hair disorder, dry skin, pruritus/urticaria, skin disorder, skin infection, and nail disorder; DEs were characterized based on type, time to onset, severity, duration, and required interventions.
Fifty-eight percent of patients treated with lapatinib monotherapy, 74% treated with lapatinib plus paclitaxel or capecitabine, and 53% in the control group developed DEs. Among patients receiving lapatinib monotherapy, 55% experienced grade 1/2 DEs, 3% had grade 3 DEs, and no grade 4 DEs were observed. The most common DE was rash (43%); all other events occurred in <or=8% of patients. Most DEs developed between days 1 and 14 of starting treatment, with a median duration of 29 days. Three percent of DEs led to lapatinib dose reduction, 7% resulted in dose interruption, and 1% led to drug discontinuation.
Most DEs in lapatinib-treated patients present early, are mild to moderate in severity, and infrequently require dose modification or treatment interruption. Lapatinib-associated DEs appear to differ clinically from those associated with EGFR TKIs in both frequency and severity.
对接受拉帕替尼（一种表皮生长因子受体（EGFR [ErbB1]）和HER2（ErbB2）的小分子双靶点酪氨酸激酶抑制剂（TKI））治疗的癌症患者的皮肤事件（DEs）进行特征描述。
本分析纳入了9项转移性癌症的临床试验。拉帕替尼的给药剂量为每日1000至1500毫克，作为单药治疗（n = 928）或与紫杉醇或卡培他滨联合使用（n = 491）。未接受拉帕替尼治疗的患者组成对照组。皮肤事件包括手足综合征、皮疹、毛发异常、皮肤干燥、瘙痒/荨麻疹、皮肤病变、皮肤感染和指甲病变；根据类型、发病时间、严重程度、持续时间和所需干预措施对皮肤事件进行特征描述。
接受拉帕替尼单药治疗的患者中有58%发生了皮肤事件，接受拉帕替尼联合紫杉醇或卡培他滨治疗的患者中有74%发生了皮肤事件，对照组中有53%发生了皮肤事件。在接受拉帕替尼单药治疗的患者中，55%经历了1/2级皮肤事件，3%发生了3级皮肤事件，未观察到4级皮肤事件。最常见的皮肤事件是皮疹（43%）；所有其他事件在≤8%的患者中发生。大多数皮肤事件在开始治疗的第1天至第14天出现，中位持续时间为29天。3%的皮肤事件导致拉帕替尼剂量减少，7%导致剂量中断，1%导致停药。
接受拉帕替尼治疗的患者中大多数皮肤事件出现较早，严重程度为轻至中度，很少需要调整剂量或中断治疗。拉帕替尼相关的皮肤事件在频率和严重程度上似乎在临床上与EGFR TKIs相关的皮肤事件有所不同。
