Phase I study of intravenous decitabine in combination with oral vorinostat in patients with advanced solid tumors and non-Hodgkin's lymphomas (NHL)
Bibliographic record
Abstract
3528 Background: Decitabine (D), a hypomethylating agent, and vorinostat (V), a histone deacetylase inhibitor, belong to two different classes of drugs with an epigenetic effect. The ideal dose scheduling of these drugs remains controversial. This phase I study aims to determine the recommended phase II dose (RPTD) of the combination, their toxicity profile, pharmacokinetic (PK) interaction and preliminary clinical activity. Methods: Patients (pts) with advanced solid tumors or relapsed/refractory NHL are eligible. Two different schedules of D and V are being evaluated: sequential administration of D followed by V and concurrent administration of D and V. Dose escalation of D and V on the sequential schedule is described in Table. Results: To date, 27 pts have been entered into dose levels 1, -1, 1a, 1b, -1b, -2b of the sequential schedule. Demographics: median age 61 (range 31–76), F:M = 13:14, ECOG 0:1:2 = 8:16:3, tumor types: 24 solid tumor and 3 NHL. Pts received a total of 77 cycles with a median of 2 cycles (range 1–8). Adverse events (AE) of grade 3 or higher of at least possible attribution to the study treatment were neutropenia (16 pts), thrombocytopenia (4), febrile neutropenia (2), fatigue (2), and 1 pt each for constipation, dehydration, nasal bleeding, elevated alanine aminotransferase, and hyponatremia. Dose limiting toxicities (DLT) consisted mainly of myelosuppression, constitutional and gastrointestinal symptoms occurred in 7/27 (26%) of pts so far. Disease stabilization for 4 or more cycles was observed in 7 out of 22 (31.8%) evaluable pts (two with breast and one each of thymus, colon, pancreatic, appendix and non-small cell lung cancers). Conclusions: The sequential combination of D and V seems to be tolerable after some adjustments in the doses and duration of drug administration. Prolonged disease stabilization has been observed in multiple tumor types. Accrual is ongoing and RPTD will likely be dose level -1b or -2b. ( Supported by NCI Grant No. U01CA132123.) [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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.002 | 0.001 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.002 | 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".