卡培他滨联合多西他赛或长春瑞滨治疗蒽环类耐药晚期乳腺癌患者的生活质量:3期临床研究

Quality of life in anthracycline-resistant advanced breast cancer patients treated by capecitabine combined with docetaxel versus vinorelbine: a phase 3 randomized trial

目的对比接受卡培他滨联合多西他赛或长春瑞滨方案治疗的蒽环类耐药晚期乳腺癌患者的生活质量差异。方法本研究是一项前瞻性、开放性、单中心随机3期临床研究,纳入2010年4月至2013年2月在中国医学科学院北京协和医学院肿瘤医院接受多西他赛联合卡培他滨(TX)或长春瑞滨联合卡培他滨(NX)治疗的蒽环类耐药晚期乳腺癌患者206例,按治疗方案的不同分为TX组和NX组。TX组患者在第1天静脉滴注多西他赛75 mg/m^2+口服卡培他滨1 g/m^2,每天2次,第1~14天,每3周重复治疗;NX组在第1、8天静脉滴注长春瑞滨25 mg/m^2+口服卡培他滨1 g/m^2,每天2次,第1~14天,每3周重复治疗。治疗6~8个周期后,有效者继续卡培他滨维持治疗。共98例患者完成肿瘤患者生活质量评分表(QOL)及乳腺癌患者生活质量测定量表(FACT-B)评分,包括TX组48例和NX组50例。采用t检验分析2组患者治疗前后生活质量评分变化,率的比较采用χ~2检验,T分期及N分期比较采用秩和检验。结果 TX组治疗前后QOL评分分别为55.08±4.64、52.58±5.38,差异有统计学意义(t=4.417,P<0.001);NX组治疗前后评分分别为53.22±4.95、50.94±5.29,差异有统计学意义(t=4.347,P<0.001)。TX组及NX组治疗前后FACT-B量表评分比较,差异均无统计学意义(95.94±17.54比93.13±16.65,t=1.826,P=0.074;94.28±14.60比91.40±12.96,t=1.956,P=0.056)。TX组及NX组晚期乳腺癌患者治疗前后生活质量评分差值比较,差异无统计学意义(QOL量表:2.50±4.18比2.42±3.83,t=0.099,P=0.921;FACT-B量表:2.40±10.45比2.88±10.41,t=-0.230,P=0.819)。QOL量表评分显示:在食欲下降、疲乏、精神状态减退、睡眠受影响方面,TX组和NX组比较,差异均有统计学意义[58.33%(28/48)比36.00%(18/50),χ~2=4.904,P=0.027;54.17%(26/48)比34.00%(17/50),χ~2=4.045,P=0.044;33.33%(16/48)和16.00%(8/50)χ~2=3.979,P=0.046;31.25%(15/48)比14.00%(7/50),χ~2=4.186,P=0.041]。FACT-B量表评分显示:TX组和NX组恶心者分别占52.08%(28/48))和22.00%(11/50),差异有统计学意义(χ~2=9.537,P=0.002);表现疼痛症状的患者分别占29.17%(14/48)和40.00%(20/50),差异无统计学意义(χ~2=1.269,P=0.260)。根据治疗后疗效评估,有效组共78例,无效组20例,2组患者治疗前后生活质量评分差值比较,差异均无统计学意义(QOL量表:2.32±4.05比3.00±3.74,t=-0.679,P=0.499;FACT-B量表:1.90±10.84比5.55±7.90,t=-1.411,P=0.161)。有效组中,发生手足综合征和未发生手足综合征患者间治疗前后生活质量评分差值比较,差异无统计学意义(QOL量表:1.50±4.37比2.53±3.98,t=-0.907,P=0.367;FACT-B量表:0.25±7.52比2.32±11.56,t=-0.679,P=0.499)。无效组20例患者中无一例出现手足综合征。结论 TX和NX方案化疗对患者生活质量影响不大,化疗疗效及手足综合征对患者生活质量的影响不显著。

Objective To compare the effect of different regimens（ capecitabine plus docetaxel vs capecitabine plus vinorelbine） on the quality of life in anthracycline-resistant advanced breast cancer patients.Methods This was a prospective, open, single-centered, phase 3 randomized trial, including 206 anthracycline-resistant advanced breast cancer patients in Cancer Hospital,Chinese Academy of Medical Sciences and Peking Union Medical College. They were treated by different regimens of chemotherapy（ capecitabine plus docetaxel vs capecitabine plus vinorelbine） and divided into two groups accordingly： TX group received intravenous infusion of 75 mg/m^2 docetaxel on day 1 and 1 g/m^2 capecitabine twice per day on days 1-14,every 3 weeks; NX group received 25 mg/m^2 vinorelbine on days 1 and 8 and 1 g/m^2 capecitabine twice per day,on days 1-14,every 3 weeks. After the treatment of 6-8 cycles,the patients with clinical response continued the maintenance treatment of capecitabine. Totally 98 patients were evaluated by quality of life（ QOL） scale and functional assessment of cancer therapy-breast cancer（ FACT-B）,including 48 patients in TX group and 50 patients in NX group. Using t test,QOL and FACT-B scores in two groups were compared before and after treatment. χ~2 test was used to compare the number of cases. The rank sum test was used to analyze the rank data.Results In TX group,QOL score was 55. 08 ± 4. 64 and 52. 58 ± 5. 38 before and after chemotherapy,indicating a significant difference（ t = 4. 417,P〈0. 001）. In NX group,QOL score was 53. 22±4. 95 and 50. 94± 5. 29 before and after treatment,indicating a significant difference（ t = 4. 347,P 〈 0. 001）.FACT-B scores showed no significant difference before and after treatment in TX group and NX group（ 95. 94±17. 54 vs 93. 13±16. 65,t = 1. 826,P = 0. 074,94. 28 ± 14. 60 vs 91. 40 ± 12. 96,t = 1. 956,P = 0. 056）. The score gap before and after treatment presented no significant difference between TX group and NX group（ QOL：2. 50±4. 18 vs 2. 42 ± 3. 83,t = 0. 099,P = 0. 921; FACT-B： 2. 40 ± 10. 45 vs 2. 88 ± 10. 41,t =-0. 230,P =0. 819）. According to QOL scores,the patients showed significant differences in the loss of appetite,fatigue,decreased mental status and affected sleep between TX and NX groups [58. 33%（ 28/48） vs 36. 00%（ 18/50）,χ~2= 4. 904,P = 0. 027; 54. 17%（ 26/48） vs 34. 00%（ 17/50）,χ~2= 4. 045,P = 0. 044; 33. 33%（ 16/48） vs16. 00%（ 8/50）,χ~2= 3. 979,P = 0. 046; 31. 25%（ 15/48） vs 14. 00%（ 7/50）,χ~2= 4. 186,P = 0. 041）.FACT-B scores showed that the proportion of nausea patients was 52. 08%（ 28/48） in TX group and 22. 00%（ 11/50） in NX group,indicating a significant difference（ !2= 9. 537,P = 0. 002）; the proportion of patients with pain symptom was 29. 17%（ 14/48） in TX group and 40. 00%（ 20/50） in NX group,indicating no significant difference（ χ~2= 1. 269,P = 0. 260）. According to the treatment outcome,78 patients showed clinical response,the chemotherapy was ineffective in 20 patients and there was no significant difference in life quality between two groups（ QOL： 2. 32±4. 05 vs 3. 00±3. 74,t =-0. 679,P = 0. 499; FACT-B： 1. 90±10. 84 vs 5. 55±7. 90,t =-1. 411,P = 0. 161）. In 78 patients with clinical response,there was no significant difference between the patients with hand-foot syndrome and the patients without（ QOL： 1. 50±4. 37 vs 2. 53±3. 98,t =-0. 907,P = 0. 367; FACT-B： 0. 25 ± 7. 52 vs 2. 32 ± 11. 56,t =-0. 679,P = 0. 499）. None had hand-foot syndrome in 20 patients with no clinical response. Conclusions TX and NX regimens of chemotherapy may have little influence on life quality of advanced breast cancer patients. The chemotherapy efficacy and the occurrence of hand-foot syndrome produce no remarkable effect on life quality of pateints.