Effects of GC4419 (avasopasem manganese) on chronic kidney disease in head and neck cancer patients treated with radiation and cisplatin.
Bibliographic record
Abstract
12071 Background: Nephrotoxicity is a major complication of platinum-based chemotherapy and ranges in incidence from 31-68%. The effects of platinum-based chemotherapeutics on long-term renal outcomes (chronic kidney disease, CKD) profoundly affect morbidity and mortality. Concurrent chemoradiotherapy (CRT) including cisplatin is standard for locally advanced squamous cell head and neck cancer (HNC) but is accompanied by the risk of CKD. In a randomized, multi-center, placebo-controlled Phase 2b trial ( NCT02508389 ) of GC4419 (avasopasem manganese) in HNC patients receiving CRT, avasopasem reduced the duration, incidence, and severity of severe oral mucositis (Anderson et al, JCO 2019). Avasopasem did not appear to alter the safety profile of CRT in that trial, including incidence of adverse events of kidney injury or azotemia. Methods: Pre- and post-treatment markers of kidney function including blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR) were retrospectively evaluated for a subset of 52 of the trial patients who received 3 cycles x 100 mg/m2 cisplatin plus placebo or 30 or 90 mg of avasopasem intravenously prior to RT, and 7 comparator patients who received the same CRT outside the study. Kidney function was evaluated between 3- and 24-months post-completion of cisplatin-radiation therapy by two-way analysis of variance (ANOVA) as defined by the Kidney Disease Improving Global Outcomes (KDIGO) CKD staging. Results: Baseline patient characteristics were skewed towards a male population but were balanced across all treatment arms with regards to baseline kidney function (comparator + placebo, n = 19; 30 mg GC4419, n = 18; 90 mg GC4419, n = 15). Treatment with 90 mg GC4419 demonstrated normal BUN values (10-20 mg/dL) at 3, 6, and 18 months and normal sCr values (0.6-1.2 mg/dL) between 3 and 24 months as compared to the placebo arm + comparator group, which exhibited statistically elevated BUN and sCr (p < 0.05). Treatment with 90 mg GC4419 also demonstrated significantly higher eGFR between 3 and 24 months post-chemoradiation (p < 0.05) compared to the placebo arm + comparator group. 90 mg GC4419 treatment significantly reduced the incidence of CKD compared to the placebo arm and comparator group, as determined by fold change in sCr values and eGFR measurements < 60 mL/min (stage G3a/b, G4, or G5 CKD). Conclusions: Avasopasem has the potential to reduce the incidence and severity of CKD in patients receiving cisplatin therapy. Clinical trial information: NCT02508389 .
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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 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.001 | 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".