Kidney and Cancer Outcomes with Standard vs. Kidney Protective Chemotherapy Regimens for First-Line Treatment of Metastatic Urothelial Carcinoma
Bibliographic record
Abstract
Background: Cisplatin-based combination chemotherapy regimen is the optimal initial treatment for metastatic urothelial carcinoma, but kidney function eligibility and nephrotoxicity are treatment-limiting for many patients. For patients unfit to receive cisplatin, other options include alternative administration schedules (e.g. split dose cisplatin), carboplatin-based regimens and non-platinum regimens. The aims of this study were to compare cancer outcomes and incidence of acute kidney injury (AKI) during treatment among 3 regimens of chemotherapy. Methods: We conducted a single-center retrospective study of patients receiving first-line chemotherapy for metastatic urothelial carcinoma (2005-2019). We compared standard gemcitabine-cisplatin (gem-cis) to: 1) gemcitabine-cisplatin split dose regimen (split) with cisplatin divided over day 1 and 8; and 2) combination of gemcitabine-carboplatin or single-agent gemcitabine (gem/gem-carbo). We used Fine and Gray hazard models accounting for baseline covariates and competing risk of death. Results: We identified 183 patients (98 gem-cis, 32 split and 53 gem/gem-carbo). Median age was 67 years-old (IQR: 61-73) and 76% were male. Median baseline eGFR was 78 mL/min/1.73m2 (IQR: 66-91) in gem-cis, 64 (48-77) in split, and 45 (33-57) in gem/gem-carbo. Patients receiving split and gem/gem-carbo were older, had worse performance status, and hypertension was more frequent. Split and gem/gem-carbo regimens were associated with higher mortality and progressive disease relative to gem-cis when adjusted for age, baseline eGFR, ECOG, hypertension and diabetes with hazard ratio (HR) of 1.56 (95%CI: 1.04-2.34; p=0.03) and 2.02 (95%CI: 1.36-3.01; p<0.01) respectively. Median time to progressive disease was 242 (IQR: 137-444), 182 (122-279) and 131 (68-257) days in gem-cis, split and gem/gem-carbo groups. There was no significant association between regimen type and AKI with HR of 1.32 (95%CI: 0.62-2.81; p=0.47) and 0.98 (95%CI:0.46-2.09; p=0.96) for split and gem/gem-carbo groups versus gem-cis. Conclusions: Kidney protective chemotherapy regimens were associated with increased disease progression and mortality, without a significant difference in AKI. Alternative kidney protective strategies are needed for patients with CKD and urothelial cancer.
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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 | 0.001 | 0.004 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 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".