Gershenson D M, Burke T W, Morris M, Bast R C, Guaspari A, Hohneker J, Wharton J T
Department of Gynecologic Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, 77030, USA.
Gynecol Oncol. 1998 Sep;70(3):404-9. doi: 10.1006/gyno.1998.5130.
To determine the toxicity and activity of intravenous vinorelbine given daily for 3 consecutive days every 3 weeks in patients with platinum-resistant epithelial ovarian cancer.
Between September 1994 and October 1995, 23 women with refractory epithelial ovarian cancer were entered onto this phase I study. All patients had measurable disease and platinum-resistant tumor, and prior therapy was limited to a maximum of two prior regimens. Nineteen (83%) were assessable for toxicity and 20 (87%) were assessable for response. Vinorelbine was administered intravenously daily for 3 consecutive days; this was repeated every 21 days. The starting dose was 20 mg/m2 daily x3, with dose escalation by 5 mg/m2 daily x3. Dose-limiting toxicity (DLT) was defined as grade 4 granulocytopenia for >3 days, grade 4 thrombocytopenia, neutropenic fever, or grade 3 or greater nonhematologic toxicity. The maximal tolerated dose (MTD) was defined as the highest dose level at which <50% of patients developed a DLT. Once the MTD of vinorelbine without granulocyte colony-stimulating factor (filgrastim) support was defined, dosing was begun at the MTD level and administration of 5 microg/kg filgrastim was initiated on day 4 and continued until WBC counts reached >10,000/microL. Clinical response, progression-free survival, and survival were also determined.
Nineteen patients evaluable for toxicity received a total of 135 cycles of vinorelbine. The major DLT was neutropenia. The MTD of vinorelbine without filgrastim support was established as 20 mg/m2 daily x3. The MTD of vinorelbine with filgrastim support was established as 25 mg/m2 daily x3. Of 20 patients evaluable for response, 2 patients (10%) had a complete response and 4 (20%) had a partial response, for an overall response rate of 30%.
These results warrant further study of vinorelbine in patients with platinum-resistant epithelial ovarian cancer. However, further study of the daily x3 schedule may not be warranted because of failure to achieve higher weekly dose intensity and because of nonhematologic toxicity in the form of intense bone pain.
确定每3周连续3天每日静脉给予长春瑞滨对铂耐药上皮性卵巢癌患者的毒性和活性。
1994年9月至1995年10月，23例难治性上皮性卵巢癌女性患者进入该I期研究。所有患者均有可测量病灶且肿瘤对铂耐药，既往治疗最多限于两种既往方案。19例（83%）可评估毒性，20例（87%）可评估反应。长春瑞滨每日静脉给药，连续3天；每21天重复一次。起始剂量为每日20mg/m²×3天，剂量以每日5mg/m²×3天递增。剂量限制性毒性（DLT）定义为4级粒细胞减少持续超过3天、4级血小板减少、中性粒细胞发热或3级及以上非血液学毒性。最大耐受剂量（MTD）定义为发生DLT的患者比例小于50%的最高剂量水平。一旦确定了无粒细胞集落刺激因子（非格司亭）支持时长春瑞滨的MTD，就在MTD水平开始给药，并于第4天开始给予5μg/kg非格司亭，持续至白细胞计数达到>10,000/μL。还确定了临床反应、无进展生存期和生存期。
19例可评估毒性的患者共接受了135个周期的长春瑞滨治疗。主要DLT为中性粒细胞减少。无非格司亭支持时长春瑞滨的MTD确定为每日20mg/m²×3天。有非格司亭支持时长春瑞滨的MTD确定为每日25mg/m²×3天。在20例可评估反应的患者中，2例（10%）完全缓解，4例（20%）部分缓解，总缓解率为30%。
这些结果值得对铂耐药上皮性卵巢癌患者进一步研究长春瑞滨。然而，由于未能实现更高的每周剂量强度以及出现严重骨痛形式的非血液学毒性，可能无需对每日×3方案进行进一步研究。
