Pharmacodynamic and safety study of reolysin in patients with advanced solid tumors
Bibliographic record
Abstract
14004 Background: Reolysin is an intravenous formulation of reovirus serotype 3 - Dearing strain which is a double stranded RNA non-enveloped icosahedral virus capable of inducing cytopathic effects in cancer cells that have an activating mutation in the ras protooncogene. Pre clinical testing has identified cancer cell lines as being susceptible to reovirus infection. Methods: This was an open- label single center phase I safety and dose escalation trial of reolysin administered intravenously over 1 hour on day 0 in a 28 day cycle. Dose escalations were in half log increments. Serum for neutralizing antibody (NA) was drawn at baseline, and days (d) 1, 7, 14, 21, and 28, and serum, stool, saliva, and urine for viral shedding (by RT-PCR) were sampled on d 1,7,14,21, and 28. Response was assessed by imaging studies after 1, 3, 5, and 7 cycles. Results: 18 patients (pt); median age 57 (40–72) years; performance status 0–1; diagnoses - ovarian (6), colorectal (5), and others (7) received 27 cycles of reolysin (median 1, range 1–7) in 6 dose cohorts of 1x108, 3x108, 1x109, 3x109, 1x1010, and 3x1010 tissue culture infective dose (TCID)50. No protocol defined dose limiting toxicities were observed. Drug related grade 2 toxicities included chills (2 pt), and fatigue (3 pt). The only grade 3 event was fever in cycle 7 in a 57 year old woman with progressive breast cancer, treated at a dose of 1x1010 TCID50. She was noted to have 28.5% shrinkage in objective tumor volume. An additional 7 pt had stable disease (SD). No NA was detectable in the serum in any pt at baseline; however all pt developed NA (on d 5 in 5 pt, d 8 in 11 pt, d 14 in 1 pt, and d 28 in 1 pt) during the course of the study. Viral shedding was observed in serum - 5 pt, stool - 3 pt, saliva - 3 pt, and urine - 4 pt. Of interest, 4 of 5 pt with viral shedding had SD as their best response. However, there was no observed relationship between NA formation and SD. Conclusion: Reolysin administered as a one hour infusion on a monthly schedule is safe and well-tolerated even in multiple doses. This preliminary data suggests there is anti-tumor activity of reolysin as a single agent, and warrants further studies either alone or in combination with cytotoxic chemotherapy. [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) | 0.000 | 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 | 0.001 |
| 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".