改良多西他赛方案治疗化疗耐受性差的前列腺癌患者的疗效和安全性分析

Modified docetaxel regimen for prostate cancer patients who got poor tolerance to chemotherapy

目的 探讨改良多西他赛＋泼尼松（docetaxel＋prednisone，DP）方案治疗化疗耐受性差的转移性去势抵抗性前列腺癌的疗效与安全性。方法回顾性分析2010年3月至2015年10月收治的50例采用DP方案治疗的转移性去势抵抗性前列腺癌患者的临床资料，其中23例因不能耐受标准DP方案毒性作用或评估为化疗耐受性差者接受改良DP方案（改良组），同期27例接受标准DP方案（标准组）。改良组和标准组的中位年龄分别为69岁（47～80岁）和63岁（52～77岁），差异有统计学意义（P＝0.005）。改良组和标准组化疗前疼痛患者分别为19例和24例；淋巴结转移分别为10例和19例，内脏转移分别为3例和4例；50例患者均合并骨转移。改良组Gleason评分≤7分者7例，≥8分者13例，未评分者3例；标准组≤7分者7例，≥8分者15例，未评分者5例。两组在疼痛、远处转移和Gleason评分方面的比较差异均无统计学意义（均P〉0.05）。采用Kaplan－Meier法比较两组患者的总生存期（overall survival，OS）、无疾病进展生存期（progression free survival，PFS）及常见毒性判断标准（CTCAE－4）≥3级不良反应发生情况。结果 改良组和标准组中位随访时间分别为11个月（3.4～35.0个月）和14个月（3.4～69.2个月）；中位化疗周期分别为4.5个（2～14个）和5.0个（2～10个）。改良组和标准组中位OS分别为18.0个月（6.7～112.0个月）和27.5个月（5.1～76.0个月），差异无统计学意义（P＝0.746）；中位PFS分别为6.0个月（1.4～15.4个月）和5.2个月（3.0～11.9个月），差异无统计学意义（P＝0.822）；出现PSA反应者分别为13例和17例（P＝0.615）；疼痛完全缓解者分别为8例和7例（P＝0.927）。改良组与标准组发生3～4级不良事件者分别为3例和14例，差异有统计学意义（P＝0.003），均无5级不良反应者。主要表现为血液毒性、中性粒细胞减少性发热、胃肠道反应、水肿、乏力和黏膜炎等，5例出现≥2个不良反应。改良组出现白细胞减少2例次，腹泻和血小板减少各1例次；标准组出现中性粒细胞减少11例次，白细胞减少4例次，血红蛋白减少和水肿各2例次，血小板减少、腹泻、恶心/呕吐、口腔黏膜炎、乏力各1例次；5例中性粒细胞减少性发热者均为标准组。 结论 与标准DP方案比较，改良DP方案在OS、PFS、疼痛缓解率和PSA反应率等方面没有差异，但≥3级不良反应发生率明显减少。

Objective To evaluate the efficacy and safety of the modified docetaxel plus prednisone scheme for the metastatic castration resistant prostate cancer patients who got poor tolerance to chemotherapy. Method The clinical data of 50 metastatic castration resistant prostate cancer who received docetaxel＋ prednisone chemotherapy from March 2010 to October 2015 were analyzed retrospectively. 23 cases received the modified DP regimen （modified group）, 27 cases received the standard DP regimen （standard group）. The median age of the modified group and the standard group were 69 years （47-80 years） and 63 years （52-77 years）（P=0.005）. There were 19 and 24 cases with pain in modified group and standard group respectively; 10 and 19 cases with lymph node metastasis respectively; 3 and 4 cases of visceral metastasis respectively; all of the 50 patients were complicated with bone metastasis. For the pathological Gleason score, there were 7 cases scored ≤7 points, 13 cases scored ≥8 points and 3 cases unscored in the modified group; 7 cases scored ≤7 points, 15 cases scored ≥8 points and 5 cases unscored in standard group. There was no significant difference of the pain, metastasis, and Gleason score between the two groups （P〉0.05）. Progression free survival（PFS）, overall survival（OS）and adverse events were analyzed using Kaplan-Meier curves, and the differences were assessed using the log-rank test. Results In the modified group and standard group, the median follow-up times were 11.0 months and 14.0 months respectively, the median chemotherapy cycles were 4.5 cycles and 5.0 cycles respectively; OS were 18.0 months and 27.5 months respectively （P=0.746）. The PFS of the two groups were 6.0 months and 5.2 months, respectively （P=0.822）. The PSA response were 13 cases and 17 cases in the modified group and standard group respectively（P=0.615）, and the pain response were 8 cases and 7 cases （P=0.927）, grade 3 to 4 adverse events were 3 cases and 14 cases （P=0.003）. The main adverse events were blood toxicity , neutrophils, gastrointestinal reaction, edema, fatigue and oral mucositis etc. Conclusions Compared with the standard DP scheme, the modified DP scheme had no significant difference in OS, PFS, pain response rate and PSA response rate, while the incidence of grade 3 to 4 adverse events was significantly reduced. Modified DP scheme may be a better choice for patients with metastatic castration resistant prostate cancer who get poor tolerance to chemotherapy.