Phase I/II trial of oncolytic reovirus (Reolysin) in combination with carboplatin/paclitaxel in patients (pts) with advanced solid cancers
Bibliographic record
Abstract
e14519 Background: Reolysin, a wild type reovirus (Dearing strain), replicates preferentially in Ras-activated cancer cells. Preclinical data have demonstrated synergistic tumor kill when reolysin is combined with standard chemotherapies including platinum agents and taxanes, justifying the clinical evaluation of this drug combination. Methods: Pts were initially treated in an open-label, dose-escalating, phase I trial and received iv reolysin, d1–5, iv carboplatin (AUC5), d1, and paclitaxel (175mg/m2), d1, qw3. Reolysin was administered at a starting dose of 3x109 TCID50 and then increased to 1x1010 and 3x1010 TCID50 in cohorts of 3 pts. Primary endpoints for the dose escalation trial were to determine the maximum tolerated dose, dose limiting toxicity (DLT) and to recommend a dose for phase II studies. Secondary endpoints were to evaluate pharmacokinetics, immune response and anti-tumour activity. The primary endpoint for the phase II expansion cohort in head and neck (H&N) pts is to characterize response rate. Results: 17 heavily pre-treated pts (11 M, median age 55 yrs) with advanced cancer: H&N (10), melanoma (4), peritoneal/endometrial cancer (2), and sarcoma (1) have received 82 cycles of treatment to date; 4 pts are still on study. There were no DLTs in the dose escalation. Toxicities were mainly grade 1 and 2 and included: nausea, fatigue, vomiting, myalgia, fever, neutropenia, lymphopenia, thrombocytopenia and hypotension. This combination resulted in a blunting of antiviral immune response as compared to monotherapy virus. Response rates in 15 evaluable patients were partial response (PR) (4 pts), stable disease (SD) (6 pts) and progressive disease (5 pts). Of note, all PRs and 4/5 SDs were in H&N disease. Conclusions: The combination of reolysin and carboplatin/paclitaxel was well tolerated and resulted in disease control in the majority of pts. Significant responses in refractory H&N pts recommended this combination for phase II evaluation. Enrollment is ongoing and randomized studies are planned. [Table: see text]
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.001 |
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".