Cetin Bulent, Benekli Mustafa, Turker Ibrahim, Koral Lokman, Ulas Arife, Dane Faysal, Oksuzoglu Berna, Kaplan Mehmet Ali, Koca Dogan, Boruban Cem, Yilmaz Burcak, Sevinc Alper, Berk Veli, Uncu Dogan, Harputluoglu Hakan, Coskun Ugur, Buyukberber Suleyman
J Chemother. 2014 Oct;26(5):300-5. doi: 10.1179/1973947813Y.0000000147. Epub 2013 Dec 6.
Lapatinib is the first dual tyrosine kinase inhibitor of human epidermal growth factor receptor type 2 (HER2/neu) and epidermal growth factor receptor (EGFR). The present study evaluated the efficacy and tolerability of the combination of lapatinib and capecitabine in patients with metastatic breast cancer (MBC) who progressed after therapy with trastuzumab, a taxane and/or anthracycline. A total of 203 patients with a median age of 48 years (range: 25-82 years) were evaluated retrospectively in 11 centres between September 2007 and May 2011. All the patients had HER2-positive MBC progressing after trastuzumab and chemotherapy including an anthracycline and/or taxane. All patients were treated with the combination of lapatinib (1250 mg/day, continuously) and capecitabine (2000 mg/m(2) on days 1 through 14 of a 21-day cycle). Data on demographics, clinical outcome, and toxicity were collected for descriptive analyses. The median follow-up was 10·7 months (range: 1-40 months). An overall response rate (ORR) of 33·4% was achieved including 7 complete responses (CR, 3·4%), 61 partial responses (PR, 30·0%), and 44 stable disease (37·9%). Clinical benefit rate of 71·3% was achieved. Median progression-free survival (PFS) was 7 months (95% CI: 6-10 months), with a median overall survival (OS) of 15 months (95% CI: 12-18 months). The most common side effects were hand-foot syndrome (46·8%), nausea (42·3%), fatigue (42·2%), anorexia (38·5%), diarrhea (31·5%), and rash (29·6%). Grade 3-4 toxicities were identified as hand foot syndrome (7·9%), diarrhea (6·9%), fatigue (5·9%), and rash (5·4%). There were no symptomatic cardiac events. Lapatinib and capecitabine combination therapy is effective and well tolerated in patients with MBC who had progressive disease after trastuzumab, taxane, and/or anthracycline therapy, as evidenced by this retrospective evaluation. Toxicity was mild to moderate with low grade 3-4 toxicity.
拉帕替尼是首个针对人表皮生长因子受体2（HER2/neu）和表皮生长因子受体（EGFR）的双靶点酪氨酸激酶抑制剂。本研究评估了拉帕替尼与卡培他滨联合用药对接受曲妥珠单抗、紫杉烷和/或蒽环类药物治疗后病情进展的转移性乳腺癌（MBC）患者的疗效和耐受性。2007年9月至2011年5月期间，11个中心对203例患者进行了回顾性评估，这些患者的中位年龄为48岁（范围：25 - 82岁）。所有患者均为HER2阳性MBC，在接受曲妥珠单抗及包括蒽环类药物和/或紫杉烷的化疗后病情进展。所有患者均接受拉帕替尼（1250 mg/天，持续给药）与卡培他滨（在21天周期的第1至14天，剂量为2000 mg/m²）联合治疗。收集人口统计学、临床结局和毒性数据进行描述性分析。中位随访时间为10.7个月（范围：1 - 40个月）。总缓解率（ORR）为33.4%，包括7例完全缓解（CR，3.4%）、61例部分缓解（PR，30.0%）和44例病情稳定（37.9%）。临床获益率为71.3%。中位无进展生存期（PFS）为7个月（95%置信区间：6 - 10个月），中位总生存期（OS）为15个月（95%置信区间：12 - 18个月）。最常见的副作用为手足综合征（46.8%）、恶心（42.3%）、疲劳（42.2%）、厌食（38.5%）、腹泻（31.5%）和皮疹（29.6%）。3 - 4级毒性反应包括手足综合征（7.9%）、腹泻（6.9%）、疲劳（5.9%）和皮疹（5.4%）。未出现有症状的心脏事件。这项回顾性评估表明，拉帕替尼与卡培他滨联合治疗对曲妥珠单抗、紫杉烷和/或蒽环类药物治疗后病情进展的MBC患者有效且耐受性良好。毒性反应为轻至中度，3 - 4级毒性反应发生率较低。
