DP方案治疗>75岁转移性去势抵抗性前列腺癌患者的疗效及安全性研究

目的探讨多西他赛+泼尼松(DP)方案治疗>75岁转移性去势抵抗性前列腺癌(mCRPC)患者的疗效及安全性。方法回顾性分析2013年2月至2019年12月北京医院收治的118例年龄≥60岁mCRPC患者的临床资料。患者中位年龄72(65,77)岁;美国东部肿瘤协作组(ECOG)评分均≤2分,G8量表评分(14.1±1.5)分,简易智力状态评估量表(Mini-Cog)评分中位值3(1,3)分;118例均出现骨转移。依据年龄将患者分为60~75岁组和>75岁组。其中60~75岁组65例,年龄67(63,71)岁;Gleason评分≤7分24例,>7分41例;61例行内分泌治疗,4例行睾丸切除术;ECOG评分0分37例,1分25例,2分3例;前列腺特异性抗原(PSA)90(35.5,258)ng/ml;G8量表评分(14.3±2.1)分;Mini-Cog评分3(2,3)分。>75岁组53例,年龄78(76, 83)岁,Gleason评分≤7分30例,>7分23例;43例行内分泌治疗,10例行睾丸切除术;ECOG评分0分5例,1分38例,2分10例;PSA 115(60,296)ng/ml;G8量表评分(13.6±1.1)分;Mini-Cog评分3(1,3)分。两组年龄、Gleason评分、去势方式、ECOG评分差异均有统计学意义(P<0.05),PSA水平、G8量表评分、Mini-Cog评分差异均无统计学意义(P>0.05)。两组患者均予DP方案化疗:多西他赛每周期予65~75mg/m²,第1天;多西他赛用药前12、3、1h予地塞米松7.5mg预处理;泼尼松5mg每天1次,第2~21天。每21天为1个周期。比较两组患者应用DP方案化疗的疗效及安全性。结果 118例均获得随访,中位随访时间21.5(6,62)个月。60~75岁组与>75岁组化疗周期数量(6.1±1.3)个与(6.8±1.7)个]、化疗剂量(70.3±4.3) mg/m²与(66.3±5.2) mg/m²]、PSA反应率72.3%(47/65)与66.0%(35/53)]、骨痛缓解率45.0%(9/20)与54.5%(6/11)]的差异均无统计学意义(P>0.05)。60~75岁组与>75岁组中位无进展生存时间6.1(1.4,11.2)个月与5.9(2.0,12.0)个月]差异无统计学意义(P>0.05)。两组均无死亡病例,60~75岁组与>75岁组应用DP方案作为一线治疗后中位总生存时间(OS)26.5(16.1,31.3)个月与24.8(17.5,28.4)个月]差异无统计学意义(P=0.223),两组应用DP方案作为二线或三线治疗后中位OS17.3(13.2,20.5)个月和15.4(12.3,20.0)个月]差异也无统计学意义(P=0.331)。60~75岁组和>75岁组3级不良反应分别为3例(4.6%)和5例(9.4%),3级白细胞减少分别为1例次(1.5%)和2例次(3.8%),3级中性粒细胞减少性发热各1例次,两组上述并发症发生率的差异均无统计学意义(P>0.05)。结论通过G8量表评分、Mini-Cog评分进行筛选,DP方案化疗对>75岁的mCRPC患者有良好的PSA反应率、骨痛缓解率及OS,且未增加不良反应发生率;年龄不应成为前列腺癌应用DP方案化疗的绝对禁忌。

Clinical efficacy and safety of docetaxel in the treatment of castration resistant prostate cancer patients over 75 years old

Objective To evaluate the efficacy and safety of docetaxel+prednisone in the treatment of castrated resistant prostate cancer in patients over 75 years old.Methods In this study,118 metastatic castration resistant prostate cancer(mCRPC)patients over 60 years old treated in Beijing Hospital from February 2013 to December 2019 were retrospectively analyzed.The median age of the patients was 72(65,77)years,ECOG scores≤2.All 118 cases had bone metastasis,5 cases had visceral metastasis.A total of 40 patients chose docetaxel as the first-line treatment of mCRPC,and the remaining 78 patients chose docetaxel as second-line or third-line treatment.The study included 53 patients>75 years old and 65 patients aged 60-75 years.The age of patients in the two groups were 67(63,71)years old and 78(76,83)years old,the difference was statistically significant(P<0.05).Among them,there were 24 cases with Gleason score≤7 and 41 cases with Gleason score>7 in 60-75 years old group,and 30 cases with Gleason score≤7 and 23 cases with Gleason score>7 in the group of>75 years old,with significant difference between the two groups(P=0.034).Sixty-one patients received endocrine therapy and 4 received orchiectomy in the 60-75 years old group;43 patients received endocrine therapy and 10 received orchiectomy in the group of>75 years old,the difference was statistically significant(P=0.035).There were 37 cases with ECOG 0 score,25 cases with 1 scores and 3 cases with 2 scores in the group of 60-75 years old;there were 5 cases with ECOG 0 score,38 cases with 1 score and 10 cases with 2 score in the group of>75 years old,with significant difference between the two groups(P<0.05).There was no significant difference in PSA level90(35.5,258)ng/ml vs.115(60,296)ng/ml],G8 scale score(14.3±2.1 vs.13.6±1.1)],Mini-Cog score3(2,3)vs.3(1,3)],and visceral metastasis2 cases(3.1%)vs.3 cases(5.7%)](P>0.05).The efficacy and safety of docetaxel in the two groups were further observed.Results The median follow-up time was 21.5(6,62)months.There was no significant difference in chemotherapy cycle(6.1±1.3)vs.(6.8±1.7)]and chemotherapy dose(70.3±4.3)mg/m² vs.(66.3±5.2)mg/m²]between the 60-75 years old group and the>75 year old group(P>0.05).The PSA response rate72.3%(47/65)vs.66.0%(35/53)],pain relief rate45.0%(9/20)vs.54.5%(6/11)],and median progression-free survival6.1(1.4,11.2)months vs.5.9(2.0,12.0)months]had no statistical significance(P>0.05).There were no deaths in the two groups during chemotherapy.The median overall survival(OS)of patients aged 60-75 years and those>75 years old who received docetaxel as first-line treatment were 26.5(16.1,31.3)months and 24.8(17.5,28.4)months,respectively(P=0.223).The median OS of the two groups were 17.3(13.2,20.5)months and 15.4(12.3,20.0)months with docetaxel treatment as second or third line treatment(P=0.331).There were 3 cases(4.6%)and 5 cases(9.4%)of grade 3 adverse reactions in 60-75 years group and>75 years old group,respectively.Grade 3 leukopenia occurred in 1 case time(1.5%)and 2 cases(3.8%)respectively.Grade 3 neutropenia fever occurred in 1 case time in both groups.There was no significant difference in the incidence of above complications between the two groups(P>0.05).Conclusions The efficacy and safety of docetaxel+prednisone chemotherapy for mCRPC patients>75 years old were similar to those of 60-75 years old.Age should not be the absolute contraindication of docetaxel for prostate cancer chemotherapy.