Britten Carolyn D, Finn Richard S, Bosserman Linda D, Wong Steven G, Press Michael F, Malik Mubashira, Lum Bert L, Slamon Dennis J
Department of Medicine, University of California, Los Angeles, CA, USA.
Clin Breast Cancer. 2009 Feb;9(1):16-22. doi: 10.3816/CBC.2009.n.003.
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.
开展这项I/II期试验以确定厄洛替尼联合曲妥珠单抗治疗转移性HER2+乳腺癌的毒性、推荐剂量、药代动力学及缓解率。
在I期，既往治疗不限的连续几组患者接受剂量水平为50、100和150mg的厄洛替尼加标准剂量的每周一次曲妥珠单抗治疗。在II期，仅允许转移性疾病既往未接受过化疗或曲妥珠单抗治疗的患者入组。
I期入组的16例患者对该联合治疗耐受性良好，II期厄洛替尼的推荐剂量最初设定为150mg。对II期前8例患者进行中期评估时发现，皮疹和腹泻的发生率高于I期预期，因此修订方案，新的II期患者接受100mg厄洛替尼治疗，并根据个体耐受性在3周后有机会增至150mg。由于针对HER2+乳腺癌的其他疗法取得进展，II期在达到入组目标前提前结束。在按照II期推荐剂量水平接受治疗的12例可评估的既往未接受过化疗和曲妥珠单抗治疗的患者中，有4例部分缓解，疾病进展时间为9.03个月（95%CI，1.2 - 未确定）。未观察到两种药物之间存在药代动力学相互作用。
根据个体患者情况调整厄洛替尼剂量时，厄洛替尼与曲妥珠单抗联合治疗耐受性良好，并有初步抗癌活性证据。
