卡培他滨联合多西他赛或长春瑞滨一线治疗三阴性乳腺癌的疗效观察

Results of phase Ⅱ study demonstrated acceptable but limited efficacy of capecitabine-based doublets in the first-line treatment of metastatic triple-negative breast cancer(mTNBC)

目的评价含卡培他滨的两药方案在复发转移性三阴性乳腺癌患者中的疗效。方法共有45例首次发现复发转移的三阴性乳腺癌患者入组,由医生决定给予卡培他滨联合多西他赛(TX方案)或是卡培他滨联合长春瑞滨(NX)方案化疗。卡培他滨1000mg/m2,口服,每天2次,第1～14天;多西他赛75mg/m2,静脉滴注,第1天;长春瑞滨25mg/m2,静脉滴注,第1和第8天,均为21天1个周期。分析患者的疗效和生存情况。结果 27名患者接受TX方案,18名患者接受了NX方案。总的客观缓解率仅为20.0%,临床获益率为62.2%。随访28个月后,中位无进展生存(PFS)为5.2个月(95%CI,4.1～6.3个月),中位总生存(OS)为18.2个月(95%CI,8.7～27.7个月)。近一半的患者(22/45)在治疗期间或治疗结束后1个月内进展。比较两个方案疗效,NX方案的客观缓解率高于TX方案(27.8%:14.8%),但差异无统计学意义(P=0.449)。同样,两者的PFS(5.2∶4.9个月,P=0.483)和OS(18.2∶21.5个月,P=0.964)也未发现统计学差异。结论尽管总生存符合预期,含卡培他滨的两药联合方案,无论是TX还是NX,就肿瘤缩小和无进展生存而言,疗效较差,提示卡培他滨在转移性三阴性乳腺癌患者中的抗癌活性有限,含卡培他滨的联合化疗方案可以用于转移性三阴性乳腺癌,但不是推荐作为首选治疗。

Objective It is extremely important to identify proper cytotoxic agents for TNBC which had limited choices except chemotherapy. Capeeitabine are well established as a major chemotherapeutic agent in metastatic setting. The efficacy of capecitabine-based chemotherapy has not been prospectively stud- ied in TNBC and data remains scant. This study was designed to investigate the efficacy of capeeitabine-based doublets in the first-line treatment of metastatic TNBC. Methods Eligible metastatic TNBC women with measurable diseases were recruited to receive either TX regimen （doeetaxel 75mg/m2, iv, dl plus capeeit- abine 1000mg/m2,bid, dl-14, q3w） or NX regimen （vinorelbine 25mg/mz, iv, dl, 8 plus capeeitabine 1000mg/m2 ,bid, dl-14, q3w） at the discretion of physicians for up to 6 cycles, until disease progression or unacceptable toxicity. The primary endpoint was objective response rate and secondary endpoints included pro- gression free survival （PFS）, overall survival （OS）. Results 45 mTNBC patients, 27 in TX and 18 in NX were recruited. The total objective response rate was 20. 0% and clinical benefit rate was 62. 2%. After a me- dian follow-up of 28 months, PFS was 5.2 months （95% CI, 4. 1-6. 3mons） and OS was 18.2months （95% CI, 8.7-27.7mons）. Almost half of the patients （22/45） progressed during treatment or within one month of the treatment discontinuation. When comparing two doublets, the response rate was numerically but not statis- tically lower in TX group than in NX group （27. 8% vs 14. 8%, P = 0. 449 ）. Similarly, no difference was found in either PFS （4. 9 vs 5.2 mons, P =0. 483） or OS （21.5 vs 18. 3 mons, P =0. 964） between two reg- imens. Conclusions Although the overall survival seems to be reasonable, efficacy of capecitabine-con- tained TX or NX regimen was relatively poor in terms of tumor remission and progression free survival in mT- NBC patients, suggesting capecitabine may have limited potency in this subtype. These two combinations may be considered to be acceptable but may not be recommended as prior choice for mTNBC patients.