Differential time course of action of 5-HT<sub>3</sub> and NK<sub>1</sub> antagonists when used with highly and moderately emetogenic chemotherapy (HEC and MEC)
Bibliographic record
Abstract
9629 Background: Cisplatin-based HEC displays a biphasic pattern of emesis with both an early and delayed period. In contrast, MEC has a monophasic pattern. The objective of this analysis was to investigate the time course of action of the 5-HT 3 antagonist ondansetron (OND) and the NK 1 antagonist aprepitant (APR) in trials with HEC and MEC. Methods: Phase III HEC and MEC trials of APR were included. In 2 HEC studies, patients (pts) scheduled to receive cisplatin- based chemotherapy were randomized to an active-control group (OND + dexamethasone [DEX] Day 1, DEX bid Days 2–4) or an APR group (APR + OND + DEX Day 1; APR + DEX qd Days 2–3; and DEX Day 4). In a third HEC study, control pts also received OND on Days 2- 3. For the MEC study, breast cancer pts receiving anthracycline + cyclophosphamide-based chemotherapy were randomized to an active- control group (OND + DEX pre chemotherapy and OND 8 hours (h) later; OND bid Days 2–3) or an APR group (APR + OND + DEX pre chemotherapy and OND 8 h later; APR qd Days 2–3). In a post-hoc analysis, multivariate logistic regression models were used to assess the impact on emesis at different time intervals using a modified intent-to-treat approach. No multiplicity adjustment was planned, so nominal p-values are reported. Results: 1,527 pts and 856 pts were randomized and assessed for efficacy in the HEC and MEC trials respectively. For HEC, APR reduced risk of emesis beginning 15–18 h after cisplatin and extending to 48 h by 45–77% compared to control and by 45–67% compared to the OND control. For MEC, APR markedly reduced emesis from 6–9 h by 61% compared to control (p=0.0012). Conclusions: Time of onset (15 h vs. 6 h) and time course (15–48 h vs. 6–9 h) for the enhanced control of emesis with the addition of APR differs between HEC and MEC respectively. With HEC these results suggest that 5-HT 3 dependent mechanisms are most important in the first 12 h after HEC with NK 1 -dependent mechanisms having a key role later. With MEC both 5-HT 3 and NK 1 mechanisms appear to be important early and the greatest impact of the NK 1 antagonist occurs in the first 9 h. These results provide a rationale for maximizing NK 1 -antagonist exposure early on with MEC as a means to improve emesis control. [Table: see text]
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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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.002 | 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".