Department of Gynecology and Obstetrics, Center for Integrated Oncology, Bonn University Medical Center, University Hospital of Bonn, Sigmund-Freud-Str 25, 53105 Bonn, Germany.
Cancer Chemother Pharmacol. 2010 May;66(1):203-7. doi: 10.1007/s00280-010-1276-2. Epub 2010 Mar 5.
Sorafenib is a novel oral anticancer agent targeting signal transduction and angiogenic pathways through inhibitory effects against MAP kinases and vascular endothelial growth factor receptor-2. The objectives of this neoadjuvant phase II-trial in patients with advanced epithelial ovarian cancer were to assess the activity and tolerability of the combination therapy of carboplatin/paclitaxel with multi-target tyrosine kinase inhibitor sorafenib.
Patients with histologically proven stage IIIC or IV disease and large volume ascites were eligible. Enrolled patients received 2 of 6 cycles carboplatin (area under the curve 5) and paclitaxel (175 mg/m(2)) preoperatively and concomitant sorafenib 400 mg twice daily. After four cycles of postoperative chemotherapy, a maintenance phase of single agent oral sorafenib through 1 year was planned. This phase II-study was planned with a sample size of 102 patients and progression-free survival as primary study endpoint.
Four patients were enrolled. After preoperative treatment and cytoreductive surgery, all patients were excluded from protocol due to severe toxicities. Three patients had life threatening events (cardiac output failure, myocardial infarction, anastomotic leak); two patients had primary progressive disease. The study was terminated on the basis of the recommendation of an independent data safety monitoring board.
The addition of sorafenib to carboplatin/paclitaxel chemotherapy was not feasible within this neoadjuvant regimen in primary advanced ovarian cancer. Although the occurrence of serious adverse events might have emerged at random, a detrimental effect of preoperative study medication could not be denied. Further evaluations of sorafenib in ovarian cancer are warranted.
索拉非尼是一种新型的口服抗癌药物，通过抑制 MAP 激酶和血管内皮生长因子受体-2 来靶向信号转导和血管生成途径。本研究旨在评估卡铂/紫杉醇联合多靶点酪氨酸激酶抑制剂索拉非尼在晚期上皮性卵巢癌新辅助治疗中的活性和耐受性。
本研究纳入组织学证实为 III C 期或 IV 期疾病且有大量腹水的患者。入组患者接受术前 6 个周期的卡铂（曲线下面积 5）和紫杉醇（175 mg/m²）治疗，以及同时给予索拉非尼 400 mg，每日两次。术后化疗完成 4 个周期后，计划进行单药口服索拉非尼维持治疗 1 年。本研究计划入组 102 例患者，无进展生存期作为主要研究终点。
共入组 4 例患者。经过术前治疗和细胞减灭术后，由于严重毒性反应，所有患者均被排除出方案。3 例患者发生危及生命的事件（心输出量衰竭、心肌梗死、吻合口漏）；2 例患者发生原发性疾病进展。根据独立数据安全监测委员会的建议，本研究提前终止。
在原发性晚期卵巢癌的新辅助方案中，卡铂/紫杉醇联合索拉非尼治疗不可行。尽管严重不良事件的发生可能是偶然的，但不能排除术前研究药物的有害作用。有必要进一步评估索拉非尼在卵巢癌中的应用。
