CN-11 * ORTERONEL (TAK-700) AND POSTERIOR REVERSIBLE ENCEPHALOPATHY SYNDROME (PRES)
Bibliographic record
Abstract
Orteronel (TAK-700), a selective oral nonsteroidal inhibitor of 17 alpha-monooxygenase (17, 20 lyase), blocks androgen synthesis of both gonadal and adrenal dehydroepiandrosterone sulfate (DHEA) and androstenedione, reduces testosterone levels in men on a GnRH agonist, and is under investigation for the treatment of prostate cancer. Common side effects include fatigue, nausea and vomiting, constipation and headache (30 %), and are usually mild. Central nervous system toxicities have not been reported. A 60 year old otherwise well man with locally advanced high-risk adenocarcinoma of the prostate (T4, N0, M0; Gleason 9/10) was treated on RTOG study 1115 with biclutamide (androgen receptor inhibitor) 50 mg po daily, leuprolide acetate (GnRH agonist) 22.5 mg sc every 3 months, and orteronel 300 mg po bid. Pelvic radiotherapy (RT) began 2 months later. Near the end of RT he developed intermittent headaches, hypertension and word finding and reading problems. Amlodipine did not improve his symptoms. A CT scan showed white matter hypodensity in the left temporal and parietal region. A MRI showed T2 and FLAIR hyperintense signal with mass effect in the left posterior temporal, parietal and occipital white matter regions, sparing the cortex, with no restricted diffusion or enhancement, and no arterial or venous abnormalities. A diagnosis of posterior reversible encephalopathy syndrome (PRES) was made. The orteronel was stopped and the neurological symptoms improved within days. A repeat MRI done 5 weeks later showed marked reduction of white matter abnormalities, with further improvement 3 months later. His symptoms have mostly resolved, but he still describes subtle cognitive problems. This is the first case of PRES associated with orteronel. Patients on orteronel who develop hypertension, headache or neurological symptoms are at risk for PRES. Hypertension should be aggressively treated, and orteronel should be stopped if symptoms persist or PRES is identified on MRI.
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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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| 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 | 0.000 | 0.000 |
| 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; a candidate call from one teacher head, 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".