du Bois A, Meier W, Lück H J, Emon G, Moebus V, Schroeder W, Costa S, Bauknecht T, Olbricht S, Jackisch C, Richter B, Wagner U
Department of Gynecology & Gynecologic Oncology, Dr-Horst-Schmidt-Kliniken Wiesbaden, Germany.
Ann Oncol. 2002 Feb;13(2):251-7. doi: 10.1093/annonc/mdf038.
The majority of patients with ovarian cancer are not cured by first-line treatment. Until now, no study could demonstrate any substantial benefit when exposing ovarian cancer patients to second-line chemotherapy. However, most treatment regimens induce toxicity, thus negatively influencing the quality of rather limited life spans. Here we evaluate whether a second-line chemotherapy can offer any benefit compared with a less toxic hormonal treatment.
Patients with ovarian cancer progressing during platinum-paclitaxel containing first-line therapy or experiencing relapse within 6 months were eligible. Patients were stratified for response to primary treatment (progression versus no change/response), and measurable versus non-measurable disease. Treatment consisted of either treosulfan 7 g/m5 infused over 30 min or leuprorelin 3.75 mg injected subcutaneously or intramuscularly. Both regimens were repeated every 4 weeks.
This study began in late 1996, and after 2.5 years accrual an interim analysis was performed when several investigators reported their concern about a suspected lack of efficacy. Following this analysis the recruitment was stopped early and the 78 patients already enrolled were followed up. The majority of patients received treatment until progressive disease was diagnosed or death occurred. Treatment delay was observed rarely and dose reduction was performed only in the treosulfan arm in 5% of 150 courses. Overall, both treatment arms were well tolerated. No objective responses were observed. The median survival time was 36 and 30 weeks in the treosulfan and leuprorelin arms, respectively. Overall survival did not differ between patients with relapse 3-6 months after first-line chemotherapy compared with patients with progressive disease within 3 months.
The selected patient population represents a subgroup with extremely poor prognosis. Accordingly, results were not impressive. Both treatment arms showed favourable toxicity data, but failed to show remarkable activity, thus adding only limited evidence to the issue of whether patients with refractory ovarian cancer might benefit from second-line chemotherapy. Even stratified analysis did not identify any subgroup of patients in whom the administration of second-line chemotherapy could demonstrate a clinically relevant survival benefit.
大多数卵巢癌患者无法通过一线治疗治愈。迄今为止，尚无研究能够证明让卵巢癌患者接受二线化疗有任何实质性益处。然而，大多数治疗方案都会引发毒性反应，从而对本就有限的生存期质量产生负面影响。在此，我们评估与毒性较小的激素治疗相比，二线化疗是否能带来任何益处。
符合条件的患者为在含铂 - 紫杉醇一线治疗期间病情进展或在6个月内复发的卵巢癌患者。患者根据对初始治疗的反应（进展与无变化/反应）以及可测量与不可测量疾病进行分层。治疗方案包括在30分钟内静脉输注曲奥舒凡7 g/m²或皮下或肌肉注射亮丙瑞林3.75 mg。两种方案均每4周重复一次。
本研究始于1996年末，在2.5年的入组期后，当几位研究者报告他们对疑似疗效缺乏的担忧时进行了中期分析。基于该分析，招募提前终止，对已入组的78例患者进行随访。大多数患者接受治疗直至诊断出病情进展或死亡。很少观察到治疗延迟，仅在曲奥舒凡组中，150个疗程中有5%进行了剂量减少。总体而言，两个治疗组耐受性良好。未观察到客观缓解。曲奥舒凡组和亮丙瑞林组的中位生存时间分别为36周和30周。一线化疗后3 - 6个月复发的患者与3个月内病情进展的患者相比，总生存期无差异。
所选患者群体代表了预后极差的亚组。因此，结果并不令人印象深刻。两个治疗组均显示出良好的毒性数据，但未显示出显著活性，因此对于难治性卵巢癌患者是否可能从二线化疗中获益这一问题，仅增加了有限的证据。即使进行分层分析，也未发现任何能证明二线化疗给药可带来临床相关生存获益的患者亚组。
