Misawa Akihiko, Yasuda Makoto
Dept. of Obstetrics and Gynecology, The Jikei University School of Medicine.
Gan To Kagaku Ryoho. 2006 Oct;33(10):1445-52.
The current initial standard chemotherapy for advanced ovarian cancer is a regimen with a combination of platinum and taxane. However, the 5-year survival rate remains at 40% or lower, and the recurrence rate is as high as 70-80%. Second-line chemotherapy for recurrent cases has not yet been established. We conducted a phase I study of combined chemotherapy with paclitaxel (TXL) and carboplatin (CBDCA) administered weekly for recurrent and refractory ovarian cancer. The subjects were patients with a histopathologically confirmed diagnosis of malignant epithelial ovarian cancer, with recurrent or refractory disease after the initial chemotherapy. TXL was administered at escalating concentrations up to 60-100 mg/m(2), while the dose of CBDCA was fixed at an AUC of 2. In regard to the dosing schedule, premedication was performed as defined before TXL administration, and TXL and CBDCA were administered, in that order, by intravenous infusion for over at least 1 hour. The 4-week period, including the administration of both drugs on Day 1, 8, and 15, was regarded as one course of treatment. No cases developed grade 4 hematoxicity, but leukopenia and neutropenia occurred. All cases of leukopenia of step 4 and step 5 developed grade 3 leukopenia. Grade 2 thrombocytopenia was one example at a low rate. Non-hematological toxicity included neuropathy, arthralgia and muscle pain, but none of the patients developed grade 3 or 4. The response rate was 41.7% (5/12). The response rate of cases administered over TXL 80 mg was 66.7% (4/6). Based on these results,the following dose schedule was recommended for planning and designing a phase II study in the future: CBDCA AUC 2+TXL 80 mg/m(2) (Days 1, 8, and 15 q 4 weeks).
目前晚期卵巢癌的初始标准化疗方案是铂类和紫杉烷类联合用药。然而，其5年生存率仍保持在40%或更低，复发率高达70 - 80%。复发病例的二线化疗方案尚未确立。我们开展了一项I期研究，针对复发和难治性卵巢癌患者进行紫杉醇（TXL）和卡铂（CBDCA）每周联合化疗。研究对象为经组织病理学确诊为恶性上皮性卵巢癌、初始化疗后复发或难治的患者。TXL以递增浓度给药，最高达60 - 100 mg/m²，而CBDCA的剂量固定为AUC 2。关于给药方案，在TXL给药前按规定进行预处理，然后依次静脉输注TXL和CBDCA，输注时间至少超过1小时。包括在第1、8和15天同时给予两种药物的4周时间被视为一个疗程。未出现4级血液毒性病例，但发生了白细胞减少和中性粒细胞减少。第4步和第5步的所有白细胞减少病例均出现3级白细胞减少。2级血小板减少发生率较低，仅1例。非血液学毒性包括神经病变、关节痛和肌肉疼痛，但无一例患者出现3级或4级。缓解率为41.7%（5/12）。TXL给药剂量超过80 mg的病例缓解率为66.7%（4/6）。基于这些结果，建议在未来规划和设计II期研究时采用以下给药方案：CBDCA AUC 2 + TXL 80 mg/m²（第1、8和15天，每4周重复）。
