脂质体多柔比星联合卡铂治疗复发性卵巢上皮性癌的临床研究

Combined pegylated liposomal doxorubicin and carboplatin in the treatment of recurrent epithelial ovarian cancer

目的评价脂质体多柔比星＋卡铂方案治疗复发性卵巢上皮性癌（卵巢癌）的疗效和副反应。方法2003年7月-2007年12月间北京肿瘤医院妇瘤科共收治67例卵巢癌（包括原发性腹膜腺癌8例，因其生物学行为和治疗同卵巢癌，故列入本研究）患者，所有患者初次治疗均接受了肿瘤细胞减灭术及以铂类为基础的联合化疗，复发后使用脂质体多柔比星（35～40mg／m^2）＋卡铂（血浆浓度时间曲线下面积=5，每4周为1个疗程）作为一线或二线及以上化疗方案治疗，观察其有效率和生存率，并且评估其化疗副反应的发生率。结果67例患者中，49例患者可进行疗效评估，其中完全缓解23例（47％），部分缓解13例（27％），病情平稳3例（6％），疾病进展10例（20％），有效（完全缓解＋部分缓解）率为73％；中位疾病无进展生存时间为8个月；1年和2年生存率分别为73％和55％。67例患者中，2例因过敏样输液反应终止治疗；4例出现胸闷为主要症状的急性输液反应（因停药后再次使用时无任何不良反应发生，所以未终止治疗）；2级和3级手足综合征分别为2例（3％）和3例（4％）；2例（3％）患者出现4级口腔炎；3级白细胞减少8例（12％）。无一例发生4级白细胞减少或与药物相关的心脏毒性反应。结论脂质体多柔比星＋卡铂方案治疗复发性卵巢癌具有一定的疗效，患者对治疗的耐受性良好，可作为治疗复发性卵巢癌的选择之一。

Objective To evaluate the efficacy and toxicity of combined pegylated liposomal doxorubicin （PLD） and carboplatin in the treatment of patients with recurrent epithelial ovarian cancer. Methods We retrospectively reviewed 67 patients with recurrent epithelial ovarian cancer or primary peritoneal adenocarcinoma （8 cases） who were treated with combined PLD and carboplatin. The response rate, survival and toxicity were evaluated. The mean age for 67 patients was 52. 1 （39 - 76） years. All of them received cytoreductive surgery followed by platinum-based chemotherapy either with paclitaxel or cyclophosphamide and doxorubicin after diagnosis. Combined PLD and carboplatin was used as first or second-line treatment or even after multiple lines of treatment after disease recurred. Patients were treated with PLD at 35 - 40 mg/m2 combined with carboplatin at an area under curve （AUC） of 5 once every 4 weeks. Results Forty-nine patients were evaluable for response. Twenty-three （47%） patients had a complete response, 13 （27%） had a partial response, 3 （6%） had stable disease and 10 （20%） had progressive disease. The estimated median progression-free survival （PFS） was 8 months. The 1-year and 2- year survival rates were 73% and 55%, respectively. All of the 67 patients were evaluated for toxicity. The treatment was terminated in 2 patients due to allergic-like infusion reaction. Four patients who had acute infusion reaction with shortness of breath and tightness of chest did not terminate the treatment because no such reaction occurred when restarted the infusion. There were 2 patients with G2 and 3 patients with G3 hand-foot syndrome, 2 patients had G4 stomatitis, and 8 patients had G3 leukopenia. No G4 leukopenia or cardiotoxicity occurred. Conclusion The combination of PLD and carboplatin is an active and welltolerated regimen in the treatment of patients with recurrent epithelial ovarian cancer.