Perifosine (P) as an active agent in the treatment of patients with advanced sarcoma
Bibliographic record
Abstract
10059 Background: Clinical benefit rate (CBR), defined as complete or partial responses (RECIST) or stable disease > 4 months, has been taken as evidence for the activity of mTOR inhibitors in sarcomas, (Chawla ASCO 2006). P is a novel oral alkylphosphocholine that targets the PI3K pathway upstream from mTOR by inhibiting the phosphorylation of Akt. (Kondapaka, Mol Cancer Ther 2003). P's activity against sarcomas has now been evaluated in 121 patients enrolled in one of 3 phase (ph) I trials or 4 ph II studies. Five of these studies have been published. All of the data are in the Keryx database from which this analysis was performed. Methods: Dose-schedules in the ph I trials were weekly (wkly) 100–800 mg; loading dose (LD) 300 - 1,800 following by daily (d) 50 - 21 every 21 days; LD 400 - 900 & d 50 - 100 continuously. In the ph II trials doses were LD 900 & d 150 every 21 days, LD 900 and d 100 continuously, d 50 mg continuously; wkly 900, wkly1200 & wkly 1,500. Regimens that included a wkly or LD of 1,200 mg or more or a d dose of ≥ 150 mg were more toxic and are defined as “higher dose” for this analysis. Results: 121 pts with sarcoma were entered on studies prior to 9/1/2006 and could be assessed for CBR. CBR is shown in the table below. Toxicities were mainly gastrointestinal and/or fatigue. The percentage of pts with grade 0 nausea (N), vomiting (V), diarrhea (D) and fatigue (F) for lower dose P was 40, 60, 45 and 57% respectively compared to 29, 38, 24 and 66% for higher dose P. The proportion of patients with grade 2+ N, V, D and F was 19, 15, 17 and 21% for lower dose P and 46, 31, 40 and 21% for higher dose P. Conclusions: In the ph I/II studies of P the CBR was 50%. This compares favorably with the activity of the mTOR inhibitors. There was no suggestion of greater activity in those given higher doses of P, but there was substantially more toxicity and greater earlier withdrawal from therapy with the higher doses. [Table: see text] No significant financial relationships to disclose.
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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) | 0.000 | 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) | 0.001 | 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".