Richard O'Dwyer , Mihaela G. Musat , Ioana Gulas , Elizabeth Hubscher , Hoora Moradian , Silke Guenther , Mairead Kearney , Srikala S. Sridhar
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引用次数: 0
Abstract
Background
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/m2 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.
Methods
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).
Results
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).
Conclusions
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.
期刊介绍:
Clinical Genitourinary Cancer is a peer-reviewed journal that publishes original articles describing various aspects of clinical and translational research in genitourinary cancers. Clinical Genitourinary Cancer is devoted to articles on detection, diagnosis, prevention, and treatment of genitourinary cancers. The main emphasis is on recent scientific developments in all areas related to genitourinary malignancies. Specific areas of interest include clinical research and mechanistic approaches; drug sensitivity and resistance; gene and antisense therapy; pathology, markers, and prognostic indicators; chemoprevention strategies; multimodality therapy; and integration of various approaches.