Department of Medical Oncology, Mount Vernon Cancer Centre, Northwood.
School of Cancer and Enabling Sciences, University of Manchester & Christie Hospital, Manchester.
Ann Oncol. 2011 Sep;22(9):2036-2041. doi: 10.1093/annonc/mdq708. Epub 2011 Jan 27.
A previous dose-escalation trial of the vascular disrupting agent combretastatin A4 phosphate (CA4P) given before carboplatin, paclitaxel, or both showed responses in 7 of 18 patients with relapsed ovarian cancer.
Patients with ovarian cancer that had relapsed and who could start trial therapy within 6 months of their last platinum chemotherapy were given CA4P 63 mg/m(2) minimum 18 h before paclitaxel 175 mg/m(2) and carboplatin AUC (area under the concentration curve) 5, repeated every 3 weeks.
Five of the first 18 patients' disease responded, so the study was extended and closed after 44 patients were recruited. Grade ≥2 toxic effects were neutropenia in 75% and thrombocytopenia in 9% of patients (weekly blood counts), tumour pain, fatigue, and neuropathy, with one patient with rapidly reversible ataxia. Hypertension (23% of patients) was controlled by glyceryl trinitrate or prophylactic amlodipine. The response rate by RECIST was 13.5% and by Gynecologic Cancer InterGroup CA 125 criteria 34%.
The addition of CA4P to paclitaxel and carboplatin is well tolerated and appears to produce a higher response rate in this patient population than if the chemotherapy was given without CA4P. A planned randomised trial will test this hypothesis.
先前进行的血管破坏剂 combretastatin A4 磷酸盐（CA4P）剂量递增试验表明，在卡铂、紫杉醇或两者联合治疗复发卵巢癌患者中，18 例患者中有 7 例出现缓解。
复发的卵巢癌患者，在末次铂类化疗后 6 个月内可以开始试验治疗，给予 CA4P 63mg/m²，最低 18 小时前给予紫杉醇 175mg/m²和卡铂 AUC（浓度曲线下面积）5，每 3 周重复一次。
前 18 例患者中的 5 例疾病得到缓解，因此该研究扩展后，在招募了 44 例患者后关闭。≥2 级毒性作用为中性粒细胞减少症（75%）和血小板减少症（9%）（每周进行血液计数）、肿瘤疼痛、疲劳和神经病变，1 例患者出现快速可逆性共济失调。高血压（23%的患者）通过甘油三硝酸酯或预防性氨氯地平控制。根据 RECIST 标准，缓解率为 13.5%，根据妇科癌症协作组 CA125 标准为 34%。
CA4P 联合紫杉醇和卡铂治疗耐受性良好，与不使用 CA4P 化疗相比，似乎在该患者人群中产生了更高的缓解率。一项计划中的随机试验将检验这一假设。
