摘要目的 探讨多西他赛治疗转移性去势抵抗性前列腺癌(mCRPC)患者的耐受剂量,以及其对患者预后的影响.方法 回顾性分析2010年3月至2016年7月收治的75例mCRPC患者的临床资料.中位年龄65岁(47 ～ 80)岁.东部肿瘤协作组(ECOG)评分≤1分50例,2分22例,3分3例.血红蛋白114 g/L(81～161)g/L.碱性磷酸酶(ALP) 133 U/L(37 ～2 154) U/L.PSA值92.3ng/ml(0.3 ～4 543.1)ng/ml.Gleason评分≤7分22例,≥8分40例,未评分8例.一线内分泌治疗有效时间平均14个月(2 ～ 96个月).患者均接受多西他赛+泼尼松化疗.根据实际接受的多西他赛剂量将患者分为低剂量组(＜ 65 mg/m2) 43例,中剂量组(65 ～70 mg/m2)21例和高剂量组(＞70mg/m2)11例.低剂量组、中剂量组、高剂量组中位年龄分别为67岁(53 ～ 80岁)、66岁(56～78岁)、61岁(47 ～ 76岁);淋巴结转移例数分别为26、13、6例;内脏及其他部位转移例数分别为11、4、2例.低剂量组2例无骨转移,余73例合并骨转移.3组的Gleason评分分别为,低剂量组≤7分15例,≥8分22例,未评分6例;中剂量组≤7分4例,≥8分13例,未评分4例;高剂量组≤7分3例,≥8分5例,未评分3例.低剂量组、中剂量组、高剂量组合并疼痛患者例数分别为36、12、9例.3组间比较,低剂量组高龄患者相对多见,差异有统计学意义(P =0.045);其他指标比较差异均无统计学意义(P＞0.05).采用Kaplan-Meier法比较3组患者的总生存期(OS)、无疾病进展生存期(PFS),以及常见毒性判断标准(CTCAE-4)≥3级不良反应发生情况.采用Cox回归模型分析影响患者OS的因素.结果 本组75例中位化疗6个周期(2 ～14个周期),平均6.1个周期.低剂量组、中剂量组、高剂量组的中位OS分别为24.1、18.5、23.5个月;中位PFS均为5.3个月,3组比较差异均无统计学(P＞0.05).低剂量组、中剂量组、高剂量组的≥3级不良反应发生率分别为34.9％ (15/43)、38.1％(8/21)、45.5％ (5/11),差异无统计学意义(P＞0.05).患者OS与一线内分泌治疗有效时间(P=0.008)、化疗前血红蛋白水平(P=0.013)、ECOG评分(P=0.018)、化疗前疼痛评分(P=0.011)、化疗周期数(P=0.001)相关,与患者年龄(P =0.953)、多西他赛剂量(P=0.086)、ALP(P=0.432)、化疗前血PSA值(P=0.231)无显著相关性.结论 多数mCRPC患者能耐受的多西他赛剂量低于标准剂量,且低剂量多西他赛化疗的疗效与高剂量相似.在患者的耐受范围内,OS与多西他赛实际剂量无显著相关性.

abstractsObjective To investigate the dose of docetaxel appropriate for patients with metastatic castration-resistant prostate cancer and its affects to the prognosis.Methods A retrospective analysis was performed on the clinical data of 75 patients with metastatic castration-resistant prostate cancer admitted from March 2010 to July 2016 who received docetaxel combined with prednisone chemotherapy.The patients were divided into the low-dose group (n =43,docetaxel ＜ 65 mg/m2),the middle-dose group (n =21,docetaxel 65-70 mg/m2) and the high-dose group (n =11,docetaxel ＞ 70 mg/m2).The median age in the low-dose group,middle-dose group and high-dose group was 67 (53-80),66 (56-78) and 61 (47-76) years old,respectively.Among 75 patients with bone metastasis,2 patients had no evidence of bone metastasis in the low-dose group.The lymph node metastasis was found in 26,13 and 6 cases in each group,respectively.And visceral and other metastasis were founded in 11,4 and 2 cases,respectively.The Gleason score in the low-dose group was≤7 points in 15 cases,≥8 points in 22 cases and no score in 6 cases.The Gleason score inthe middle-dose group was ≤7 points in 4 cases,≥8 points in 13 cases and no score in 4 cases.The Gleason score in the high-dose group was ≤7 points in 3 cases,≥8 points in 5 cases and no score in 3 cases.The number of patients with pain in the low-dose group,middle-dose group and high-dose group was 36,12 and 9,respectively,there were no significant differences in the above indicators (P ＞ 0.05),except age,which showed relatively more aged patients in the low-dose group,(P =0.045).Kaplan-Meier method was used to compare the overall survival (OS),progression-free survival (PFS) and the incidence of ≥CTCAE-4 grade 3 adverse reactions between the two groups.The Cox regression model was adopted to analyzed the factors that might affect patient prognosis,including the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,age,dose of docetaxel and alkaline phosphatase (ALP).Kaplan-Meier method was used to analyze the effect of dose of docetaxel on the prognosis,and log-rank method was used to test the significance of the results.Results The median OS was respectively 24.1,18.5 and 23.5 months in the low-dose group,middle-dose group and high-dose group,respectively.The median PFS was 5.3 months in all three groups,which didn't show statistically significant differences.The incidence of grade 3/4 adverse reactions in the low-dose group,middle-dose group and high-dose group was 15 cases (34.9％),8 cases (38.1％) and 5 cases (45.5％) respectively.It showed an increasing trend,but no statistically significant difference.The single factors related to OS mainly include the effective time of first-line endocrine therapy,hemoglobin level,ECOG score,pain score,number of cycles of chemotherapy,there was no significant correlation with age,docetaxel dose,ALP and PSA value.Conclusions It is common to receive lower doses of docetaxel in clinical practice for patients with metastatic castration-resistant prostate cancer in China.The efficacy of low-dose docetaxel is similar to that of high doses (standard dosage).There was no significant correlation between the OS and the actual dose of docetaxel in the tolerable range.