Split-Dose Cisplatin in Patients With Locally Advanced or Metastatic Urothelial Carcinoma: A Systematic Literature Review and Network Meta-Analysis
Bibliographic record
Abstract
In patients with locally advanced/metastatic urothelial carcinoma unable to tolerate standard dose gemcitabine plus cisplatin (GC), split-dose GC with the cisplatin dose divided over 2 days is potentially an alternate regimen, but clinical studies with split-dose GC are limited.Here, we report data from published clinical and real-world studies of split-dose GC and show that the effectiveness of split-dose GC appears comparable to standard cisplatin-based regimens.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/m 2 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 3.5-9.9months, 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.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.015 | 0.004 |
| Bibliometrics | 0.000 | 0.003 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; both teacher heads agree on what is shown here.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".