Tropé C, Kristensen G, Kisic J, Kaern J
Department of Gynecologic Oncology, The Norwegian Radium Hospital, Montebello, Oslo.
Eur J Gynaecol Oncol. 2001;22(3):223-7.
There is still a need for newer non-cross-resistant agents and combinations to be tried in cases of failure after first line platinum-based therapy. Several agents have demonstrated activity after failure of platinum-containing regimens. Response rate in true platinum refractory disease up to 20% but with poor long-term survival, has been reported by single drug paclitaxel. In an effort to improve response rate and survival duration obtainable with single drug paclitaxel, we have combined paclitaxel with doxorubicin for the treatment of patients refractory to cisplatin-cyclophosphamide.
Between October 1994 and November 1996, 23 patients whereof 21 refractory to cisplatin-cyclophosphamide were enrolled for toxicity and survival analysis after receiving the combination doxorubicin 50 mg/m2 and paclitaxel 135 mg/m2 every third week for four courses. Responding patients continued on single drug paclitaxel 175 mg/m2 every third week until unacceptable toxicity or tumor progression occurred.
The objective response rate (CR + PR) was 33%, 95% CI (14.6-57). The median duration of response was 8.5 months (range 4.0-62.5+) and the median overall survival was 15.5 months (range 4.0-63.5+). No serious toxicity was registered.
Doxorubicin combined with paclitaxel could safely be administered using this schedule. This study shows that some patients obtaining CR can be rendered disease-free for a substantial period of time, sometimes five years or more. A median overall survival of 15.5 months with a 5-year survival probability of 15% is impressive. However, although responses can be induced in a significant number of patients, the survival figures remain poor.
对于一线铂类治疗失败的病例，仍需要尝试更新的非交叉耐药药物及联合用药方案。几种药物在含铂方案失败后已显示出活性。据报道，单药紫杉醇治疗真正的铂类难治性疾病时，缓解率高达20%，但长期生存率较低。为了提高单药紫杉醇的缓解率和生存时间，我们将紫杉醇与阿霉素联合用于治疗对顺铂-环磷酰胺耐药的患者。
1994年10月至1996年11月，23例患者（其中21例对顺铂-环磷酰胺耐药）在接受每三周一次、共四个疗程的阿霉素50mg/m²和紫杉醇135mg/m²联合治疗后，进行毒性和生存分析。缓解的患者继续接受每三周一次的单药紫杉醇175mg/m²治疗，直至出现不可接受的毒性或肿瘤进展。
客观缓解率（完全缓解+部分缓解）为33%，95%置信区间（14.6-57）。中位缓解持续时间为8.5个月（范围4.0-62.5+），中位总生存期为15.5个月（范围4.0-63.5+）。未记录到严重毒性。
按照此方案联合使用阿霉素和紫杉醇可安全给药。本研究表明，一些获得完全缓解的患者可在相当长一段时间内无病生存，有时可达五年或更长时间。中位总生存期为15.5个月，5年生存概率为15%，令人印象深刻。然而，尽管能在相当数量的患者中诱导出缓解，但生存数据仍然较差。
