Kim Hyunho, Lee Seung-Hwan, Kim Dong Hwan, Lee Ji Youl, Hong Sung-Hoo, Ha U-Syn, Kim In-Ho
Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, St. Vincent's Hospital, Suwon, Republic of Korea.
Division of Medical Oncology, Department of Internal Medicine, The Catholic University of Korea, Seoul St. Mary's Hospital, Seoul, Republic of Korea.
Transl Androl Urol. 2020 Oct;9(5):2113-2121. doi: 10.21037/tau-20-772.
Gemcitabine with platinum is one of the most important first-line treatments for metastatic urothelial cancer (mUC). However, continuation of platinum agents results in cumulative toxicities, such as nephrotoxicity, ototoxicity, and neurotoxicity, which lead to discontinuation of chemotherapy after 4-6 cycles despite a favorable response in the patients. The strategy of maintenance treatment can give clinical benefit to patients, but there is no consensus about maintenance treatment. The aim of this study was to investigate the clinical impact of the gemcitabine maintenance (GEM-m) in mUC patients who achieve disease control from first-line gemcitabine with platinum agents.
A total of 117 patients who showed response to 4-6 cycles of gemcitabine plus cisplatin or carboplatin as the first-line palliative chemotherapy were reviewed between 2014 to 2018. Patients who were treated with GEM-m received a 1,000 mg/m dose of gemcitabine on day 1 and 8 for 3 weeks until disease progression or development of unacceptable toxicity. The patients who are not treated with GEM-m were followed up with regular radiologic evaluation. Statistical analyses were performed using the log-rank test and Cox proportional hazards method.
Fifty-eight patients (49.6%) received GEM-m. The median cycle of GEM-m was 4 (range, 1-12). Six patients (10.3%) in the GEM-m group showed an objective response. A median overall survival (OS) of 11.8 months and 9.6 months was observed for the GEM-m and non-GEM-m groups, respectively [HR 0.621; 95% CI, 0.39-0.97; P=0.026]. Additionally, median progression-free survival (PFS) was 4.6 months and 3.3 months in the GEM-m and non-GEM-m groups, respectively [HR 0.612; 95% CI, 0.41-0.91; P=0.009]. Grade 3 or higher neutropenia occurred in 17.2% of patients in the GEM-m and 1.7% in the non-GEM-m group.
Our results suggest that GEM-m can be considered in patients who respond to gemcitabine with platinum. Large-scale prospective study should be warranted.
吉西他滨联合铂类是转移性尿路上皮癌（mUC）最重要的一线治疗方案之一。然而，持续使用铂类药物会导致累积毒性，如肾毒性、耳毒性和神经毒性，这使得患者在4 - 6个周期后尽管反应良好但仍需停止化疗。维持治疗策略可为患者带来临床益处，但关于维持治疗尚无共识。本研究的目的是调查吉西他滨维持治疗（GEM - m）对一线接受吉西他滨联合铂类药物治疗且疾病得到控制的mUC患者的临床影响。
回顾了2014年至2018年间117例对4 - 6周期吉西他滨联合顺铂或卡铂一线姑息化疗有反应的患者。接受GEM - m治疗的患者在第1天和第8天接受1000mg/m²剂量的吉西他滨，持续3周，直至疾病进展或出现不可接受的毒性。未接受GEM - m治疗的患者进行定期影像学评估随访。采用对数秩检验和Cox比例风险法进行统计分析。
58例患者（49.6%）接受了GEM - m治疗。GEM - m的中位周期数为4（范围1 - 12）。GEM - m组中有6例患者（10.3%）出现客观反应。GEM - m组和非GEM - m组的中位总生存期（OS）分别为11.8个月和9.6个月[风险比（HR）0.621；95%置信区间（CI），0.39 - 0.97；P = 0.026]。此外，GEM - m组和非GEM - m组的中位无进展生存期（PFS）分别为4.6个月和3.3个月[HR 0.612；95% CI，0.41 - 0.91；P = 0.009]。GEM - m组17.2%的患者出现3级或更高等级的中性粒细胞减少，非GEM - m组为1.7%。
我们的结果表明，对于对吉西他滨联合铂类有反应的患者可考虑采用GEM - m治疗。有必要开展大规模前瞻性研究。
