Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-Ku, Okayama, Japan.
Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Kita-Ku, Okayama, Japan.
Urol Oncol. 2021 Oct;39(10):731.e25-731.e32. doi: 10.1016/j.urolonc.2021.02.029. Epub 2021 Mar 26.
This study aimed to clarify the efficacy and toxicity of first-line combination treatment with paclitaxel, cisplatin, and gemcitabine (PCG) for advanced/metastatic urothelial carcinoma (UC) in cisplatin-unfit patients compared with cisplatin-fit patients.
We conducted a retrospective study of patients who received first-line PCG. Using international consensus criteria, patients were classified into cisplatin-fit and -unfit groups. Cisplatin-unfit patients received PCG with adjustment of the cisplatin dose after assessing 24-hour urinary creatinine clearance, without modifying the administration interval.
From 2008 to 2017, 50 patients received first-line PCG, of whom 30 and 20 were classified into the cisplatin-fit and -unfit groups. After a median follow-up of 15.0 months, the median overall survival (OS) and progression-free survival (PFS) were 15.0 and 9.8 months in all patients, 15.0 and 10.0 months in the cisplatin-fit group, and 13.2 and 9.3 months in the cisplatin-unfit group, respectively. There was no significant difference in OS (hazard ratio [HR]: 1.33, 95% confidence interval [CI]: 0.69-2.54) or PFS (HR: 1.38, 95% CI: 0.74-2.55) between the groups. The overall response rate and complete response rate were 58% (95% CI: 43.2-71.8) and 32% (95% CI: 19.5-46.7) in all patients, and 55% (95% CI: 31.5-76.9) and 35% (95% CI: 15.4-59.2) in the cisplatin-unfit group, respectively. The common grade 3 of 4 adverse events experienced were neutropenia (78%), followed by thrombocytopenia (56%), anemia (46%), and febrile neutropenia (16%). The 24-hour urinary creatinine clearance did not differ significantly between the groups after one, two, or three courses of PCG.
We found no significant difference regarding OS and PFS between the cisplatin-fit patients with a full dose of cisplatin and -unfit patients with cisplatin-dose-adjusted chemotherapy. In select cisplatin-unfit patients, PCG with dose adjustment of cisplatin may be useful for treating advanced/metastatic UC without any significant adverse events or impaired renal function compared with cisplatin-fit patients with a full dose of cisplatin.
本研究旨在明确与顺铂适宜患者相比，对于不适合顺铂的晚期/转移性尿路上皮癌（UC）患者，一线联合紫杉醇、顺铂和吉西他滨（PCG）治疗的疗效和毒性。
我们对接受一线 PCG 治疗的患者进行了回顾性研究。根据国际共识标准，患者被分为顺铂适宜和不适宜组。不适合顺铂的患者在评估 24 小时尿肌酐清除率后，调整顺铂剂量，而不改变给药间隔，接受 PCG 治疗。
2008 年至 2017 年间，50 例患者接受了一线 PCG 治疗，其中 30 例和 20 例分别被归入顺铂适宜和不适宜组。中位随访 15.0 个月后，所有患者的中位总生存期（OS）和无进展生存期（PFS）分别为 15.0 和 9.8 个月、顺铂适宜组为 15.0 和 10.0 个月、顺铂不适宜组为 13.2 和 9.3 个月。两组间 OS（风险比 [HR]：1.33，95%置信区间 [CI]：0.69-2.54）或 PFS（HR：1.38，95%CI：0.74-2.55）均无显著差异。所有患者的总缓解率和完全缓解率分别为 58%（95%CI：43.2-71.8）和 32%（95%CI：19.5-46.7），顺铂不适宜组分别为 55%（95%CI：31.5-76.9）和 35%（95%CI：15.4-59.2）。所有患者中常见的 3-4 级不良事件为中性粒细胞减少症（78%），其次为血小板减少症（56%）、贫血症（46%）和发热性中性粒细胞减少症（16%）。PCG 治疗 1、2 或 3 个疗程后，两组间 24 小时尿肌酐清除率无显著差异。
我们发现，与接受全剂量顺铂的顺铂适宜患者相比，接受顺铂剂量调整的化疗的不适合顺铂的患者在 OS 和 PFS 方面无显著差异。在选择的不适合顺铂的患者中，与接受全剂量顺铂的顺铂适宜患者相比，PCG 联合顺铂剂量调整可能是一种有用的治疗方法，不会出现明显的不良反应或肾功能损害，可用于治疗晚期/转移性 UC。
