替吉奥治疗卡培他滨耐药转移性乳腺癌的疗效分析

Therapeutic Efficiency of Tegafur, Gimeracil and Oteracil Potassium for Metastatic Breast Cancer Resistant to Capecitabine

目的分析卡培他滨单药治疗耐药后的转移性乳腺癌患者接受替吉奥单药治疗的疗效及安全性。方法回顾性分析2011年11月—2015年5月宁波大学医学院附属医院肿瘤内科治疗的22例转移性乳腺癌患者的临床资料。22例患者接受卡培他滨单药治疗,在卡培他滨耐药后接受替吉奥单药治疗,直至疾病进展、不可耐受的毒副作用或患者拒绝治疗。按照实体瘤疗效评价标准(RECIST)进行替吉奥临床疗效评价,观察进展时间(TTP)及总生存期(OS),记录疼痛评分及CA153水平,根据美国国家癌症研究所发布的常见不良反应事件评价标准(CTCAE v4.02)进行毒副作用评价。结果 22例卡培他滨耐药的转移性乳腺癌患者接受替吉奥治疗后5例部分缓解,12例疾病稳定,5例疾病进展,客观有效率(ORR)为22.7%(5/22),临床获益率(CBR)为77.3%(17/22);中位TTP为113 d(22~218 d),中位OS为20.2个月(3.8~38.2个月)。替吉奥治疗前有15例患者有疼痛表现,未经提高止痛药物剂量,治疗后10例患者疼痛减轻。开始替吉奥治疗时CA153水平与治疗过程中最低CA153水平比较,差异有统计学意义[(174.8±67.4)U/ml与(102.8±69.7)U/ml,t=4.174,P=0.001]。替吉奥治疗的毒副作用均可耐受,主要毒副作用有厌食[59.1%(13/22)]、恶心[50.0%(11/22)]、乏力[45.5%(10/22)]、中性粒细胞计数减少[45.5%(10/22)]、贫血[40.9%(9/22)]、腹泻[36.4%(8/22)]、手足综合征[27.3%(6/22)]、转氨酶升高[22.7%(5/22)]及呕吐[18.2%(4/22)]等。毒副作用多为Ⅰ~Ⅱ级,仅3例发生Ⅲ级毒副作用。结论替吉奥单药对于卡培他滨单药耐药的转移性乳腺癌有一定的疗效,而且耐受性良好。因此,对于使用卡培他滨单药治疗后耐药的转移性乳腺癌可考虑选用替吉奥单药治疗。

Objective The purpose of this study is to analyze retrospectively the therapeutic efficiency and safety of tegafur,gimeracil and oteracil potassium monotherapy in patients with metastatic breast cancer resistant to capecitabine monotherapy. Methods We retrospectively ananlyzed the clinical data of 22 cases of patients with metastatic breast cancer in the Department of Medical Oncology,the Affiliated Hospital of School of Medicine Ningbo University between November 2011 and May 2015. All patients accepted capecitabine monotherapy, then they all accepted tegafur, gimeracil and oteracil potassium monotherapy after resistant to capecitabine until tumor progression,intolerable side effects and toxicity or refusal of treatment. The therapeutic efficiency of tegafur,gimeracil and oteracil potassium was evaluated according to the Response Evaluation Criteria in Solid Tumors（ RECIST）,and then the time to progression and overall survival were observed. The pain score and CA153 value were also recorded. Side effects and toxicities were assessed according to the common terminology criteria for adverse events（ CTCAE v4. 02） issued by the National Cancer Institute. Results Five patients had partial remission,12 had stable disease,and 5 had disease progress in 22 patients with capecitabine-resistant metastatic breast cancer after tegafur,gimeracil and oteracil potassium treatment. Objective response rate was 22. 7%（ 5/22）,clinical benefit response was 77. 3%（ 17/22）. Median time to progression was 113 days（ 22-218 days）,median overall survival was 20. 2 months（ 3. 8-38. 2 momths）. A total of 15 patients complained of pain before tegafur,gimeracil and oteracil potassium therapy. Pain relief happened in 10 cases without the increase of analgesic drugs dosage after therapy. Compared with the CA153 value on the beginning of tegafur,gimeracil and oteracil potassium therapy,the lowest CA153 value in the course of therapy decreased signifcantly [（ 174. 8 ± 67. 4） U/ml vs.（ 102. 8 ± 69. 7） U/ml,t = 4. 174,P = 0. 001]. The toxic side effects of tegafur,gimeracil and oteracil potassium were well tolerated,and major adverse reactions included anorexia [59. 1%（ 13/22） ], nauseas [50. 0%（ 11/22） ], fatigue[45. 5%（ 10/22） ],neutropenia [45. 5%（ 10/22） ],anemia [40. 9%（ 9/22） ],diarrhea [36. 4%（ 8/22） ],hand-foot syndrome [27. 3%（ 6/22） ],transaminase elevation [22. 7%（ 5/22） ]and vomiting [18. 2%（ 4/22） ] et al. Most adverse reactions were Grade Ⅰ-Ⅱ adverse events,Grade Ⅲ adverse events only occurred in 3 cases. Conclusion Tegafur,gimeracil and oteracil potassium monotherapy is effective and well-tolerated in patients with metastatic breast cancer resistant to capecitabine monotherapy. So tegafur,gimeracil and oteracil potassium monotherapy is a selective regime treatment for patients with metastatic breast cancer after they were resistant to capecitabine monotherapy.