Kang Heeseok, Kim Tae-Joong, Lee Yoo-Young, Choi Chel Hun, Lee Jeong-Won, Bae Duk-Soo, Kim Byoung-Gie
Department of Obstetrics and Gynecology, Medical Foundation Baek-Song, Good Morning Hospital, KyungKi-Do, Republic of Korea.
Gynecol Oncol. 2009 Aug;114(2):210-4. doi: 10.1016/j.ygyno.2009.04.016. Epub 2009 May 14.
The aim of this trial was to investigate the efficacy and toxicity of a relative high-dose of topotecan combined with carboplatin in recurrent or persistent epithelial ovarian cancer (EOC).
Patients participating in this phase II trial received topotecan at a dose of 1.0 mg/m(2)/day intravenously (IV) on days 1 to 5 in combination with carboplatin AUC 5 IV on day 5, every 21 days. The primary outcome was response rate (RR) and the toxicity. The secondary measurements were duration of response, time to progression (TTP) and overall survival (OS).
Fifty-nine patients entered the study and 53 were assessable for response. For this study, 260 courses of topotecan and carboplatin were given (median, 4 per patient; range, 1-8). The overall RR was 26.4%. The median duration of response and TTP were 7 and 6 months, respectively. The median OS was 19 months with a median follow-up period of 14 months. Initial platinum sensitivity and treatment free interval (TFI) >or=6 months were associated with RR and OS. In the platinum-sensitive group, RR and OS were 40.0% and 25 months, whereas in the platinum-resistant group, these were 8.7% and 11 months, respectively. Grade 4 neutropenia occurred in 40.7% of the patients, and grade 4 thrombocytopenia was seen in 32.2% with a bleeding event in two patients. Nonhematologic toxicities were mild. There were no drug-related toxic deaths.
The relative high-dose of topotecan combined with carboplatin was feasible and produced modest activity in recurrent or persistent EOC. The RR and survival data appear promising for the initially platinum-sensitive cohort and thus this regimen may be considered for further development in this patient.
本试验旨在研究相对高剂量的拓扑替康联合卡铂治疗复发或持续性上皮性卵巢癌(EOC)的疗效和毒性。
参与本II期试验的患者在第1至5天接受静脉注射拓扑替康,剂量为1.0mg/m²/天,第5天联合静脉注射卡铂,AUC为5,每21天重复一次。主要结局指标为缓解率(RR)和毒性。次要测量指标为缓解持续时间、疾病进展时间(TTP)和总生存期(OS)。
59例患者进入研究,53例可评估缓解情况。本研究共给予260疗程的拓扑替康和卡铂(中位数,每位患者4个疗程;范围,1 - 8个疗程)。总体RR为26.4%。缓解持续时间和TTP的中位数分别为7个月和6个月。OS的中位数为19个月,中位随访期为14个月。初始铂敏感性和无治疗间期(TFI)≥6个月与RR和OS相关。在铂敏感组中,RR和OS分别为40.0%和25个月,而在铂耐药组中,分别为8.7%和11个月。40.7%的患者发生4级中性粒细胞减少,32.2%的患者出现4级血小板减少,2例患者发生出血事件。非血液学毒性较轻。无药物相关的毒性死亡。
相对高剂量的拓扑替康联合卡铂是可行的,在复发或持续性EOC中产生了适度的活性。RR和生存数据对于初始铂敏感队列似乎很有前景,因此该方案可考虑在该类患者中进一步开展研究。