Homocysteine (HC) level as possible predictor of pemetrexed efficacy
Bibliographic record
Abstract
20078 Background: Pemetrexed is a novel anticancer agent clinically active in several solid tumors, including malignant pleural mesothelioma (MPM), non-small cell lung cancer (NSCLC), and breast cancer. Pemetrexed’s anticancer activity is believed to be related to its inhibition of 3 enzymes involved with folate metabolism and DNA synthesis. Some side effects associated with its clinical activity are more pronounced if a patient (pt) has a folate deficiency and high HC levels (Niyikiza et al, Ann Oncol 1998). Given this connection, we hypothesized that high HC levels might predispose a pt to pemetrexed anticancer activity. In a related question, we examined if baseline HC levels varied among different cancers. Methods: To investigate these hypotheses, plasma HC levels were examined from pts in the pemetrexed-containing arm of a phase III MPM trial (N = 226; Vogelzang, JCO 2003); a phase III NSCLC trial (N = 265; Hanna, JCO 2004); and a phase II breast cancer trial (data pooled from 600 and 900 mg/m2 groups) (N = 92; Llombart, ASCO 2006). For each study, HC (high vs low) was used as a prognostic indicator variable for overall survival (OS) and progression-free survival (PFS). Different cut points distinguished pts with high vs low HC, and final analysis results were based on the optimal cut point that yielded the largest Wald chi-square value (smallest p-value). Results: Average baseline HC levels were similar for each trial: 11.0, 10.6, and 10.6 μmol/L for the MPM, NSCLC, and breast trial, respectively. The MPM data suggested that high HC pts had longer OS (all hazard ratios [HRs] <1). The NSCLC data showed comparable OS times regardless of HC level. MPM and NSCLC data for PFS was similar to OS results. PFS from the breast cancer study was also similar for both HC groups (HR ∼1). Conclusions: Average baseline HC level did not suggest differences in nutritional status of the 3 pt populations. Data examination from the 3 studies yielded contradictory results, suggesting that high HC level is not a predictor of a better efficacy response to pemetrexed. [Table: see text] [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 | 0.003 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.001 |
| 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".