A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach.
A phase I/II trial of trastuzumab plus erlotinib in metastatic HER2-positive breast cancer: a dual ErbB targeted approach.
复制标题
DOI：
10.3816/cbc.2009.n.003
复制
发表时间：
2009-03
影响因子：
3.1
通讯作者：
Slamon DJ
中科院分区：
文献类型：
--
作者：
Britten CD;Finn RS;Bosserman LD;Wong SG;Press MF;Malik M;Lum BL;Slamon DJ
本I/II期试验旨在确定厄洛替尼联合曲妥珠单抗治疗转移性HER 2+乳腺癌的毒性、推荐剂量、药代动力学和缓解率。在I期研究中，既往治疗不受限制的患者连续分组接受厄洛替尼50、100和150 mg剂量水平加标准剂量曲妥珠单抗每周一次。在II期研究中，仅允许既往未接受过化疗或曲妥珠单抗治疗的转移性背景患者。在I期入选的16例患者中，该组合耐受性良好，厄洛替尼的II期推荐剂量最初设定为150 mg。在对II期的前8例患者进行中期审查后，发现皮疹和腹泻的发生率高于I期经验的预期，对方案进行了修订，以厄洛替尼100 mg治疗新的II期患者，并有机会在3周后根据个体患者的耐受性递增至150 mg。由于针对HER 2+乳腺癌的其他疗法的进展，II期在达到其累积目标之前关闭。在12例接受推荐II期剂量水平治疗的可评价化疗和曲妥珠单抗初治患者中，有4例部分缓解，至进展时间为9.03个月（95% CI，1.2-未确定）。未观察到2种药物之间的药代动力学相互作用。当厄洛替尼的剂量根据个体患者的经验定制时，厄洛替尼和曲妥珠单抗的组合耐受性良好，并且有抗癌活性的初步证据。
This phase I/II trial was conducted to determine the toxicities, recommended dose, pharmacokinetics, and response rate of erlotinib plus trastuzumab in metastatic HER2+ breast cancer. In phase I, sequential groups of patients with unlimited previous treatment received erlotinib at dose levels of 50, 100, and 150 mg plus standard dose weekly trastuzumab. In phase II, only patients with no previous chemotherapy or trastuzumab in the metastatic setting were allowed. The combination was well tolerated among the 16 patients enrolled in phase I, and the recommended phase II dose of erlotinib was initially set at 150 mg. After an interim review of the first 8 patients in phase II revealed a higher incidence of rash and diarrhea than expected from the phase I experience, the protocol was amended to treat new phase II patients at erlotinib 100 mg, with the opportunity to escalate to 150 mg after 3 weeks, based on individual patient tolerability. As a result of advances in other therapies aimed at HER2+ breast cancer, phase II closed before meeting its accrual goal. Among the 12 evaluable chemotherapy- and trastuzumab-naive patients treated at the recommended phase II dose level, there were 4 partial responses, and the time to progression was 9.03 months (95% CI, 1.2-undetermined). No pharmacokinetic interaction between the 2 agents was observed. The combination of erlotinib and trastuzumab was well tolerated when the dose of erlotinib was tailored to individual patient experience, and there was preliminary evidence of anticancer activity.