Characterizing the risk of drug-drug interactions in patients receiving enzalutamide for castration-resistant prostate cancer.
Bibliographic record
Abstract
261 Background: Enzalutamide (E) is an androgen receptor antagonist used to treat castration-resistant prostate cancer (CRPC). It inhibits various cytochromes (e.g. CYP2C8), or induces others (e.g. CYP3A4). Since these CYPs are involved in the metabolism of other widely-used medications, E may expose a significant number of patients to drug-drug interactions (DDI). These DDI may diminish the efficacy of E or concurrent medications, or they may increase the risk of DDI-related adverse events (AE); but the scale of E-related DDI is not yet established. Methods: We retrospectively reviewed pharmacy records and electronic patient charts to retrieve individual drug histories, comorbidities, and on-treatment AE of CRPC patients starting E between Oct 2012 and Apr 2014. Baseline medications of individual patients were analyzed for potential DDI using two commercial databases, Lexicomp and Micromedex. Results: 69 informative patients were identified. Using Lexicomp, the most common DDI flagged as being of potential clinical significance (i.e. “avoid combination”, or “consider therapy modification”) were with amlodipine, atorvastatin, tamsulosin, ondansetron, and oxycodone administered to 12 (17%), 12 (17%), 10 (14%), 5 (7%), and 5 (7%) patients, respectively. Micromedex identified a moderate risk for amlodipine and oxycodone. At baseline, 38/69 patients (55%; Lexicomp) and 24/69 patients (35%; Micromedex) used ≥ 1 drug at risk for clinically significant DDI with E. The most common AE were fatigue in 36 patients (52%), decreased appetite in 15 (22%), peripheral oedema and weight loss each in 13 (19%), and back pain in 10 (14%). There was no conclusive evidence to link these AE to DDI. One patient had recurring episodes of hypertension, a possible result of a DDI between E and nifedipine (Lexicomp/Micromedex class “avoid”/”major”). Conclusions: The risk of clinically relevant E-related DDI in CRPC patients seems substantial, yet the selection of flagged drugs is database-dependent. Further investigations with larger populations are warranted to understand the clinical relevance of these DDI more clearly.
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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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.002 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| 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".