Juravinski Cancer Centre, Hamilton, Ontario, Canada.
Gynecol Oncol. 2010 Sep;118(3):308-12. doi: 10.1016/j.ygyno.2010.05.005. Epub 2010 Jun 19.
Approximately 50% of ovarian cancers have elevated levels of epidermal growth factor receptor (EGFR) which correlates with a poor prognosis. Preclinical evidence suggests that EGFR tyrosine kinase inhibitors (TKIs), such as erlotinib (OSI-774), may potentiate the anti-tumour effects of cytotoxic agents, including carboplatin. Blocking EGFR could thus potentially reverse drug resistance. The primary objective of the study was to assess the response rate to the addition of erlotinib in patients with recurrent ovarian cancer who were receiving carboplatin.
Patients enrolled on this study had either local or advanced recurrent ovarian cancer with measurable disease. They may have had up to 2 prior chemotherapy regimens, one of which must have contained platinum, and they must have responded to prior platinum therapy. Patients were stratified by platinum sensitivity and were treated with erlotinib 150 mg daily on a continuous dosing schedule, and carboplatin at an AUC of 5 every 21 days.
Fifty patients with recurrent ovarian cancer entered the study, 33 in the platinum-sensitive arm and 17 in the platinum-resistant arm. Of patients evaluable for response, there were 14 partial responses (PR) of 30 evaluable for response (57% objective response rate (ORR)) in the platinum-sensitive arm, and 1 PR of 14 evaluable for response (7% ORR) in the platinum-resistant arm.
The combination of erlotinib and carboplatin was active in patients with platinum-sensitive disease, but not in platinum-resistant disease. The toxicities seen were those expected with carboplatin and erlotinib.
约 50%的卵巢癌患者表皮生长因子受体（EGFR）水平升高，这与预后不良相关。临床前证据表明，EGFR 酪氨酸激酶抑制剂（TKI），如厄洛替尼（OSI-774），可能增强包括卡铂在内的细胞毒性药物的抗肿瘤作用。因此，阻断 EGFR 可能潜在地逆转耐药性。该研究的主要目的是评估在接受卡铂治疗的复发性卵巢癌患者中添加厄洛替尼的反应率。
参与该研究的患者患有局部或晚期复发性卵巢癌，且有可测量的疾病。他们可能已经接受了多达 2 种先前的化疗方案，其中一种必须含有铂，并且他们必须对先前的铂治疗有反应。患者根据铂敏感性进行分层，并接受厄洛替尼 150mg 每日连续剂量方案，以及卡铂 AUC 为 5，每 21 天一次。
50 例复发性卵巢癌患者进入研究，33 例为铂敏感组，17 例为铂耐药组。可评估疗效的患者中，铂敏感组中有 30 例可评估疗效的患者中有 14 例部分缓解（PR）（57%的客观缓解率（ORR）），而铂耐药组中有 14 例可评估疗效的患者中有 1 例 PR（7%的 ORR）。
厄洛替尼联合卡铂在铂敏感疾病患者中具有活性，但在铂耐药疾病患者中无效。观察到的毒性与卡铂和厄洛替尼的预期毒性一致。
