Abstract B242: A phase I/II study of oncolytic reovirus plus chemotherapy (carboplatin/paclitaxel) in patients with advanced solid tumors (with emphasis on patients with squamous cell carcinoma of the head and neck (SCCHN)
Bibliographic record
Abstract
Abstract Background: Reovirus is a double-stranded RNA virus which replicates in cells with activated Ras signaling pathway, while sparing normal cells. Following our recent study of intravenous (i.v.) reovirus in patients with advanced malignancies1, we have conducted a Phase I/II dose escalation study of i.v. reovirus in combination with chemotherapy. Methods: REOLYSIN® was administered to cohorts of 3 patients in escalating doses (3 × 109, 1 × 1010, 3 × 1010 TCID50) on days 1–5 while carboplatin AUC 5 and paclitaxel 175 mg/m2 were administered on day 1 of a 3-weekly schedule. Eligible patients had good performance status (ECOG PS: 0–2) with advanced cancers which were not amenable to curative treatment or were refractory to standard therapy for which paclitaxel/carboplatin was appropriate palliative chemotherapy. Results: Twenty-three patients (15 males, median age 56.9 years) with head and neck cancer (n=17), melanoma (n=4) or peritoneal/endometrial cancer (n=2) received 106 cycles (median 6, range 1–8) of combination treatment. In the dose-escalation phase of the study, there were no dose-limiting toxicities. Grade 3/4 toxicities included anaemia, leucopenia, neutropenia, lymphopenia, thrombocytopenia, infection and hypotension. Viral shedding (as assayed by reverse transcription PCR) has been documented in 2 patients. Neutralising anti-reovirus antibody responses have been measured using a previously reported technique2 and will be presented. In the Phase 1 study partial responses (PR) were noted in one of four patients with melanoma and in two of five patients with head and neck cancer. An expanded cohort of head and neck cancer patients was therefore treated at the maximum dose level (3 × 1010 TCID50) in order to further assess tumor response in this setting. To date, 14 patients with head and neck cancer have received at least two cycles and are evaluable for response. Most of them were refractory to previous platinum-based chemotherapy for recurrent/metastatic disease. PR was seen in 6 patients (43%), SD in 5 (36%) and PD in 3 (21%). The study is ongoing. Conclusion: Intravenous administration of reovirus in combination with carboplatin/paclitaxel is a safe and well-tolerated combination with promising anticancer activity in SCCHN. Further evaluation of this combination in a randomized Phase III trial in SCCHN is planned. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B242.
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 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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 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".