Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer
Cediranib, an Oral Inhibitor of Vascular Endothelial Growth Factor Receptor Kinases, Is an Active Drug in Recurrent Epithelial Ovarian, Fallopian Tube, and Peritoneal Cancer
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DOI：
10.1200/jco.2009.23.2777
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发表时间：
2009-11-20
影响因子：
45.3
通讯作者：
Penson, Richard T.
中科院分区：
文献类型：
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作者：
Matulonis, Ursula A.;Berlin, Suzanne;Penson, Richard T.
血管生成在上皮性卵巢癌（EOC）的生长中起重要作用，阻断血管生成可使EOC消退。Cediranib是一种口服酪氨酸激酶抑制剂（TKI）的血管内皮生长因子受体（VEGFR）-1，VEGFR-2，VEGFR-3，和c-kit.Patients和MethodsWe进行了II期研究cediranib复发性卵巢癌或腹膜或输卵管癌; cediranib作为每日口服剂量，和原始剂量为45毫克每天。由于在前11例患者中观察到毒性，剂量降低至30 mg。合格性包括16周，或CA-125无进展> 16周），这是主要终点，为30%; 8例患者（17%; 95% CI，7.6%至30.8%）PR，6例患者（13%; 95% CI，4.8%至25.7%）SD，无CR。11例患者（23%）在两个周期前因毒性而退出研究。3级毒性（> 20%的患者）包括高血压（46%）、疲劳（24%）和腹泻（13%）。43%的患者发生2级甲状腺功能减退。4级毒性包括CNS出血（n = 1）、高甘油三酯血症/高胆固醇血症/脂肪酶升高（n = 1）和脱水/肌酐升高（n = 1）。无肠穿孔或瘘管发生。中位PFS为5.2个月，中位OS尚未达到;中位随访时间为10.7 months.ConclusionCediranib在复发性卵巢上皮癌，输卵管癌和腹膜癌中具有活性，与其他TKI观察到可预测的毒性。
PurposeAngiogenesis is important for epithelial ovarian cancer (EOC) growth, and blocking angiogenesis can lead to EOC regression. Cediranib is an oral tyrosine kinase inhibitor (TKI) of vascular endothelial growth factor receptor (VEGFR)-1, VEGFR-2, VEGFR-3, and c-kit.Patients and MethodsWe conducted a phase II study of cediranib for recurrent EOC or peritoneal or fallopian tube cancer; cediranib was administered as a daily oral dose, and the original dose was 45 mg daily. Because of toxicities observed in the first 11 patients, the dose was lowered to 30 mg. Eligibility included 16 weeks, or CA-125 nonprogression > 16 weeks), which was the primary end point, was 30%; eight patients (17%; 95% CI, 7.6% to 30.8%) had a PR, six patients (13%; 95% CI, 4.8% to 25.7%) had SD, and there were no CRs. Eleven patients (23%) were removed from study because of toxicities before two cycles. Grade 3 toxicities (> 20% of patients) included hypertension (46%), fatigue (24%), and diarrhea (13%). Grade 2 hypothyroidism occurred in 43% of patients. Grade 4 toxicities included CNS hemorrhage (n = 1), hypertriglyceridemia/hypercholesterolemia/elevated lipase (n = 1), and dehydration/elevated creatinine (n = 1). No bowel perforations or fistulas occurred. Median PFS was 5.2 months, and median OS has not been reached; median follow-up time is 10.7 months.ConclusionCediranib has activity in recurrent EOC, tubal cancer, and peritoneal cancer with predictable toxicities observed with other TKIs.