A phase I study of reolysin given intravenously to patients with advanced malignancies
Bibliographic record
Abstract
3064 Background: Reovirus is a double-stranded RNA virus with minimal pathogenicity in humans that selectively replicates in cells with activated Ras. Activated Ras inhibits the anti-viral effects of double stranded RNA-activated protein kinase (PKR). Reovirus serotype 3 Dearing has selective antitumor activity, in vitro and in tumour xenograft models. Methods: Reolysin was administered as a 1-hr IV infusion every 4-weeks initially for one day; then 3 days then 5-days every 4 weeks. The starting dose was 1×108 tissue culture infectious dose (TCID50) increasing in successive cohorts until observation of drug-related toxicity ≥ grade 2. Endpoints were safety, viral replication, viral shedding, evaluation of immune response and antitumor activity. Results: 24 patients (pts) (median age 60; ECOG 1, 16 males) have been entered into the first 7 cohorts at the following dose levels: 1×108 for 1-day, 1×108 for 3-days and 1×108, 3×108, 1×109, 3×109 and 1×1010 TCID50 for 5-days. A maximum tolerated dose (MTD) has not been reached and no dose-limiting toxicities have been observed. Toxicities have been mild (grade 1 or 2) and have included chills, fever, headache, runny nose, fatigue and myelosuppression. Reverse transcription polymerase chain reaction (RT-PCR) studies of blood, urine, stool and sputum post reovirus administration were negative for viral shedding for all treated pts. All but one pt had neutralising anti-reovirus antibodies detectable pre-treatment. Titres increased after 1-week of treatment and remained high during subsequent courses of treatment. Two pts with metastatic colorectal cancer treated at 3×108 and 3×109 TCID50 had CEA tumour marker reduction by 60% and 27% receiving 6 and 3 courses of treatment respectively. One pt with metastatic pancreatic cancer received 4 courses of treatment with stable disease. One pt with metastatic prostate cancer had a 50% decrease in PSA after treatment at 3×109 TCID50, with evidence of tumor necrosis on CT scanning. Intratumoral reovirus replication has been detected by electron microscopy in tumur biopsies. Conclusions: Reolysin is well tolerated with minimal toxicity. No viral shedding has been detected. Virus-induced tumor necrosis associated with intratumor viral replication after systemic delivery has been observed. [Table: see text]
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.002 | 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 | 0.003 |
| 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".