Early Phase I Results for 4-Demethyl-4-cholesteryloxypenclo-medine [DM-CHOC-PEN] as Therapy in Adolescent and Young Adult (AYA) Subjects with Advanced Malignancies
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
4-Demethyl-4-cholesteryloxycarbonylpenclomedine (DM-CHOC-PEN) is a poly-chlorinated pyridine carbonate with a MOA via bis-alkylation of DNA @ N7-guanine and N4-cytosine that has completed adult clinical Phase I and II trials in individuals with malignancies involving the CNS. We report here objective clinical observations seen in a clinical Phase I DM-CHOC-PEN trial with AYA subjects that have cancer (some of which had CNS involvement). Subjects & Methods: DM-CHOC-PEN was administered as a single 3-hr IV infusion once every 21 days in escalating doses from 50 - 98.7 mg/m2 to individuals (aged 15-39 years of age) with advanced malignancies. Results: Twelve (12) AYA individuals have been treated to date (with or without CNS involvement). The drug was well tolerated with fatigue (17%) being the most common adverse effect. No neuro/cognitive, liver dysfunction, hematological, cardiac, renal or GI toxicities were observed. Pharmacokinetic profiling revealed higher AUCs for all dose levels (50-98.7 mg/m2) than had been seen previously in adults. Three (3) AYA individuals treated (1 each with NSCLC, ALL, and astrocytoma involving the CNS) have responded with CR/PR (RECIST 1.1), improved QOL/PFS (Kaplan-Meier) and OS from 8 to 35+ mos. Conclusion: DM-CHOC-PEN is safe in doses of 50-98.7 mg/m2 and produced objective responses with improved OS and manageable toxicities in AYA individuals with malignancies involving the CNS. Complete data on subject responses and observed toxicities will be presented. The data support a 3-stage mechanism for tumor cytotoxicity: entry into the CNS and into the tumor via reversible binding to RBC membranes; then transported into cancer cells with L-glutamine; and bis-alkylation as described above.
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.
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 | 0.001 | 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 it