Oral vorinostat (suberoylanilide hydroxamic acid, SAHA) in relapsed diffuse large B-cell lymphoma (DLBCL): Final results of a phase II trial
Bibliographic record
Abstract
18511 Background: Vorinostat (Zolinza™) is a histone deacetylase inhibitor (HDACI) approved in the US for the treatment of cutaneous manifestations in patients (pts) with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following 2 systemic therapies. Clinical responses with vorinostat have been reported in other lymphoma subtypes. Methods: Open-label, single-arm, nonrandomized Phase II trial of oral vorinostat 300 mg bid (initially 14 d/3 wks; amended to 3 d/wk) until disease progression or intolerable toxicity. Eligibility: measurable, relapsed/refractory DLBCL; = 2 prior systemic therapies; adequate hematologic, hepatic and renal function. Pts who had prior HDACI treatment, allogeneic transplant, or had failed > 3 prior therapies were excluded. Primary endpoint: objective response rate (ORR) measured by CT/PET. Secondary endpoints: assessment of response duration (DOR), time to progression (TTP), time to response (TTR) and safety. Results: Eighteen pts (median age, 66 y [range, 59–86 y]; median 2 prior systemic therapies) were enrolled from 5/05 - 3/06 at 8 centers. Seven pts were initially treated with 300 mg bid 14 d/3 wks, but 4 had DLT (Gr 3 muscle spasms; Gr 4 thrombocytopenia, n = 3). The schedule was amended to 300 mg bid 3 d/wk and no other pt had DLT. One pt on the 3d/wk schedule achieved a CR (TTR = 85 d; DOR = 225+ d) and the ORR was 5.6%. One pt had SD for 301 d. Sixteen pts discontinued (DC) due to PD; median TTP for all pts was 44 d. Median number of treatment cycles was 2 (range, 1–14+). Two pts received > 6 cycles (126 d). Common drug-related adverse experiences (AE; mostly = Gr 2) were diarrhea (61%), fatigue (50%), nausea (39%), anemia (33%) and vomiting (33%). Three pts had dose reduction (300 -> 200 mg bid 14 d/3 wks) and none DC due to a drug-related AE. Drug-related AE = Gr 3 included thrombocytopenia (n = 3; 300 mg bid 14 d/3 wk) and asthenia (n = 2; 300 mg bid 3 d/wk). Two pts died on study of causes unrelated to drug: PD + GI hemorrhage (d 40) and acute myocardial infarction (d 95). Conclusion: Vorinostat has modest activity in pts with relapsed DLBCL and is well tolerated at 300 mg bid 3 d/wk or 200 mg bid 14 d/3 wks. The optimal dose/schedule and predictive response biomarkers require further study. No significant financial relationships to disclose.
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 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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 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) | 0.003 | 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".