Clinical outcomes with split-dose cisplatin-based regimens in patients (pts) with locally advanced or metastatic urothelial carcinoma (la/mUC): Results of a systematic literature review (SLR) and network meta-analysis (NMA).
Bibliographic record
Abstract
589 Background: Gemcitabine + cisplatin (GC) is one of the most effective and commonly used regimens in la/mUC. In GC, cisplatin is dosed at 70 mg/m2 on day 1 of a 3-week cycle; however, for many pts, impaired renal or cardiac function, neuropathy, or poor performance status can preclude use of cisplatin. A promising alternative is split-dose GC, where the cisplatin dose is divided over 2 days. We conducted an SLR and NMA to better understand outcomes, toxicity, and comparative effectiveness of split-dose GC vs GC, GCarboplatin (GCa), and methotrexate + vinblastine + doxorubicin + cisplatin (MVAC). Methods: An SLR, performed on March 8, 2023, followed Cochrane guidelines to identify observational studies of treated pts with la/mUC and randomized and nonrandomized trials investigating split-dose cisplatin regimens for this indication. No limits were placed on publication year or geography, and studies reported in English, Spanish, French, and German were included. An NMA was conducted for objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Results were reported as odds ratios or hazard ratios (HRs) with 95% credible intervals (Crls). Results: Among 120 studies that met SLR inclusion criteria, 16 (6 clinical trials, 10 retrospective studies) conducted in the US, Europe, and Asia published from 1999-2023, representing 1,767 pts, included split-dose GC. Common reasons for choosing split-dose GC were impaired renal function (creatinine clearance ≤60 mL/min), age >70 years, comorbidities, and physician preference. Most often, cisplatin was split (35 mg/m2) on days 1+8 or 1+2, and pts received a median of 3-5 cycles. In studies reporting outcomes with split-dose GC (12 studies), ORRs were 39-80% (11 studies), median PFS was 3.5-9.9 months (7 studies), and median OS was 8.5-18.1 months (11 studies). Discontinuation rates due to adverse events were 8-38% (5 studies). In the NMA, ORR for split-dose GC was significantly higher than GCa but not GC and MVAC. PFS and OS for split-dose GC were not significantly different from GCa, GC, or MVAC (Table). Conclusions: This is the first SLR and NMA of split-dose GC in la/mUC. Despite heterogeneity in the limited studies included, survival with split-dose GC was numerically better than GC and worse versus MVAC but not statistically different in either case. Split-dose GC has the potential to extend the la/mUC population eligible to receive cisplatin-based regimens and warrants further study. [Table: see text]
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.013 | 0.025 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.011 | 0.030 |
| Bibliometrics | 0.006 | 0.007 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.002 | 0.002 |
| Open science | 0.001 | 0.002 |
| Research integrity | 0.002 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 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; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
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".