多西他赛联合贝伐珠单抗及其单药维持治疗转移性乳腺癌的临床观察

Observation of bevacizumab combined with docetaxel and bevacizumab maintained alone for metastatic breast cancer

目的探讨多西他赛联合贝伐珠单抗一线治疗序贯应用贝伐珠单抗单药维持治疗转移性乳腺癌的疗效和安全性。方法 8例转移性乳腺癌患者均为女性,年龄34～62岁,中位年龄为53岁,均经改良根治术后病理组织学确诊,免疫组化检查HER-2为(-)或(+)。治疗方案:贝伐珠单抗15mg/kg d1,多西他赛75mg/m2d1,3周为1周期。治疗6个周期未出现病情进展者应用贝伐珠单抗(15mg/kg)单药维持治疗,每3周1次。结果全组8例中获CR 1例,PR 3例,SD 4例。有效率(RR)为50%,疾病控制率(DCR)为100%。7例经联合治疗6～9个周期后用贝伐珠单抗维持治疗,维持治疗时间为2～31.3个月,中位维持治疗时间为15.3个月,中位无进展生存期为22.3个月。全组5例发生3、4级中性粒细胞减少,其中2例伴发热;5例患者出现指甲毒性,其中3例1、2级,2例3级。贝伐珠单抗应用4～36.5个月过程中,1例发生血栓3级,1例高血压2级,1例高血压3级,2例蛋白尿2级。结论多西他赛联合贝伐珠单抗一线治疗序贯应用贝伐珠单抗单药维持治疗HER-2阴性转移性乳腺癌的疗效好,毒副反应可耐受,值得临床进一步应用。

Objective To discuss the efficacy and safety of bevacizumab combined with docetaxel for metastatic breast cancer patients,and observe the efficacy and safety of bevacizumab maintenance therapy in patients with no progression after combination therapy.Methods The whole group was composed with 8 cases,all female,34-62 year-old,and the median age was 53 year-old.All the cases were diagnosed as breast cancer by histopathology after modified radical mastectomy.HER-2 tested by immunohistochemistry were all（＋） or（-）.All patients in the group were accepted with bevacizumab（15mg/kg,iv,d1） and docetaxel（75mg/m2,iv,d1） and 3 weeks was a cycle.If no porogression has been detected after 6 cycles of the combination therapy,bevacizumab（15mg/kg,per 3 weeks） was applied alone as maintenance therapy until disease progression or intolerance due to adverse effect.Results All cases could be evaluated,1 case for CR,3 cases for PR,and 4 cases for SD.RR（response rate） was 50%,and DCR（disease control rate） was 100%.Seven cases were received bevacizumab maintenance therapy after 6-9 cycles’ combination therapy.The maintenance time was 2-31.3 months;the median maintenance time was 15.3 months.The median progress free survival（PFS） was 22.3 months.Five cases occured grade 3-4 granulocytopenia,in which 2 cases occured fever.Five cases occured nail toxicity,in which 3 cases were grade 1-2,2 cases were occured grade 3.And all these conditions were relieved after the removal of docetaxel.In the 4-36.5 months of the bevacizumab alone maintenance therapy,1 cases occured thrombus（grade 3）,1 case occured hypertension（grade 2）,1 case occured hypertension（grade 3） and 2 cases occured proteinuria（grade 2）.Conclusion Bevacizumab combined with docetaxel and bevacizumab maintained alone can significantly prolong the PFS in advanced HER-2 negative breast cancer patients.All cases of the group are well tolerated with long-term bevacizumab treatment.