O'Dwyer Richard, Musat Mihaela G, Gulas Ioana, Hubscher Elizabeth, Moradian Hoora, Guenther Silke, Kearney Mairead, Sridhar Srikala S
Department of Medicine, Division of Medical Oncology, Princess Margaret Cancer Centre, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Evidence, Value and Access, Health Economics and Outcomes Research, Cytel, Waltham, MA, USA.
Clin Genitourin Cancer. 2024 Dec;22(6):102176. doi: 10.1016/j.clgc.2024.102176. Epub 2024 Jul 25.
Gemcitabine plus cisplatin (GC) is a highly active and commonly used regimen in locally advanced/metastatic urothelial carcinoma (la/mUC). With GC, cisplatin is dosed at 70 mg/m on day 1 of a 3-week cycle; however, for many patients, impaired renal or cardiac function, neuropathy, or poor performance status (PS) can preclude the use of cisplatin. A promising alternative is split-dose GC, in which the cisplatin dose is divided over 2 days.
We conducted a systematic literature review (SLR) and network meta-analysis (NMA) to better understand treatment patterns and comparative effectiveness and safety of split-dose GC vs gemcitabine plus carboplatin (GCa), GC, and methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC).
Among 120 identified studies, 16 studies representing 1,767 patients included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function, age > 70 years, comorbidities, and physician preference. Split-dose GC had objective response rates (ORRs) of 39%-80%, median progression-free survival (PFS) of 3.5-9.9 months, and median overall survival (OS) of 8.5-18.1 months. Discontinuation rates due to adverse events were 5%-38%. In the NMA, ORR with split-dose GC was significantly higher than with GCa. PFS and OS for split-dose GC were similar to that observed with the other regimens (GCa, GC, and MVAC).
This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, split-dose GC demonstrated comparable effectiveness and safety profile to those seen with other regimens. Split-dose GC thus has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further prospective study.
吉西他滨联合顺铂（GC）是局部晚期/转移性尿路上皮癌（la/mUC）中一种活性很高且常用的治疗方案。采用GC方案时，顺铂在3周周期的第1天给药，剂量为70mg/m²；然而，对于许多患者来说，肾功能或心功能受损、神经病变或体能状态（PS）较差会妨碍顺铂的使用。一种有前景的替代方案是分剂量GC，即顺铂剂量分2天给予。
我们进行了一项系统文献综述（SLR）和网状Meta分析（NMA），以更好地了解分剂量GC与吉西他滨联合卡铂（GCa）、GC以及甲氨蝶呤、长春花碱、阿霉素和顺铂（MVAC）相比的治疗模式、相对有效性和安全性。
在120项纳入研究中，有16项研究（代表1767例患者）纳入了分剂量GC。选择分剂量GC的常见原因是肾功能受损、年龄>70岁、合并症以及医生的偏好。分剂量GC的客观缓解率（ORR）为39%-80%，中位无进展生存期（PFS）为3.5-9.9个月，中位总生存期（OS）为8.5-18.1个月。因不良事件导致的停药率为5%-38%。在NMA中，分剂量GC的ORR显著高于GCa。分剂量GC的PFS和OS与其他方案（GCa、GC和MVAC）观察到的相似。
这是首次对la/mUC中使用分剂量GC进行的SLR和NMA。尽管纳入的有限研究存在异质性，但分剂量GC显示出与其他方案相当的有效性和安全性。因此，分剂量GC有可能扩大适合接受基于顺铂方案治疗的la/mUC患者群体，值得进一步开展前瞻性研究。
