University of Wisconsin Carbone Cancer Center, Madison, USA.
Clin Colorectal Cancer. 2011 Mar 1;10(1):57-62. doi: 10.3816/CCC.2011.n.008.
Metastatic colorectal cancer (mCRC) is a leading cause of cancer-related mortality in the United States, and new treatment options are needed. This phase I study investigated a novel regimen combining 2 chemotherapy drugs with proven efficacy in mCRC (capecitabine and oxaliplatin) with a tyrosine kinase inhibitor (lapatinib). Lapatinib has already been approved by the US Food and Drug Administration for treatment of selected cases of breast cancer.
Patients with solid tumors responsive to fluoropyrimidines or oxaliplatin were eligible for enrollment. Treatment was given over a 21-day cycle with a fixed dosing of intravenous oxaliplatin of 130 mg/m(2) on day 1. Capecitabine and lapatinib were given orally at escalating doses, starting at capecitabine 1500 mg/m(2)/day on days 1-14 and lapatinib 1000 mg daily on days 1-21.
Ten patients received treatment per study protocol. All had received previous systemic treatment. Diarrhea was one of the most common side effects and accounted for nearly all grade 3/4 toxicity. The starting dose level was determined to be the maximum tolerated dose. One patient with pancreatic cancer had evidence of a partial response. Three other patients demonstrated stable disease. There were no complete responses.
Results of this study suggest the regimen of capecitabine, oxaliplatin, and lapatinib has some efficacy in types of advanced or metastatic solid malignancies with known responsiveness to fluoropyrimidines or oxaliplatin. Further research may help determine whether this regimen can improve on the response rates seen with current standard regimens for mCRC.
转移性结直肠癌（mCRC）是美国癌症相关死亡的主要原因，需要新的治疗选择。这项 I 期研究调查了一种新的方案，该方案结合了两种在 mCRC 中具有疗效的化疗药物（卡培他滨和奥沙利铂）和一种酪氨酸激酶抑制剂（拉帕替尼）。拉帕替尼已被美国食品和药物管理局批准用于治疗某些乳腺癌。
对氟嘧啶或奥沙利铂有反应的实体瘤患者有资格入组。治疗方案为每 21 天一个周期，第 1 天给予固定剂量的 130mg/m2 静脉注射奥沙利铂。卡培他滨和拉帕替尼口服，剂量递增，第 1-14 天卡培他滨剂量为 1500mg/m2/天，第 1-21 天拉帕替尼剂量为 1000mg/天。
按照研究方案，共有 10 名患者接受了治疗。所有患者均接受过先前的全身治疗。腹泻是最常见的副作用之一，几乎所有 3/4 级毒性均由腹泻引起。起始剂量水平被确定为最大耐受剂量。一名胰腺癌患者有部分缓解的证据。另外 3 名患者表现为疾病稳定。没有完全缓解。
这项研究的结果表明，卡培他滨、奥沙利铂和拉帕替尼的方案在已知对氟嘧啶或奥沙利铂有反应的晚期或转移性实体恶性肿瘤中具有一定疗效。进一步的研究可能有助于确定该方案是否能提高目前 mCRC 标准方案的反应率。
