A randomized, open-label, phase II study of MDV3100 alone or in combination with leuprolide and dutasteride as neoadjuvant therapy to prostatectomy in intermediate and high-risk prostate cancer.
Bibliographic record
Abstract
TPS4695 Background: MDV3100 is a potent androgen receptor (AR) signaling inhibitor (ARSI) that inhibits AR signaling via three mechanisms: inhibition of androgen binding to AR, inhibition of AR nuclear translocation, and inhibition of nuclear AR-DNA binding. In vivo, MDV3100 induces significant prostate cancer apoptosis, an effect not seen with anti-androgens. To date, the use of neoadjuvant androgen deprivation therapy has not led to an improvement in time to PSA progression (Soloway 2002; Aus 2002). While serum androgens may be suppressed using luteinizing hormone-releasing hormone agonists, intratumoral levels of androgens remain, driving continued AR signaling and prostate cancer survival. More effective inhibition of AR signaling may improve local and systemic disease control. Methods: MDV3100-07 will assess the effect of 6 mos of neoadjuvant AR blockade with AR inhibition alone (MDV3100) or in combination with maximal suppression of androgens (MDV3100 +leuprolide [L] + dutasteride [D]). Eligible patients will have treatment-naive localized prostate cancer and be candidates for radical prostatectomy. Patients must have either PSA > 10 ng/mL or Gleason score ≥ 7 (4 + 3) with ≥3 cores containing tumor. Patients with evidence of metastatic/nodal disease are excluded. All patients receive MDV3100 (160 mg/d PO); those randomized to MDV3100+L+D therapy also receive L (22.5mg IM q3m) and D (0.5 mg/day PO). Serum/tumor androgen levels will be serially assessed. Tissue from the diagnostic and prostatectomy specimens will be evaluated for androgen levels, AR signaling profiles, and selected markers of apoptosis and mitotic indices. The primary efficacy endpoint is pathological complete response (pCR) rate at time of radical prostatectomy. For each arm, the percent of patients who achieve a pCR will be compared to the percent pCR in patients treated with neoadjuvant leuprolide, estimated to be 5% in a mixed low-to-intermediate risk population. Target Accrual: 40 pts will be randomized 1:1 to MDV3100 or MDV3100+L+D therapy. Keywords:MDV3100, prostate cancer, androgen receptor, anti-androgen, Phase 2, neoadjuvant.
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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 | 0.002 | 0.001 |
| Meta-epidemiology (narrow) | 0.002 | 0.001 |
| Meta-epidemiology (broad) | 0.003 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.002 |
| Scholarly communication | 0.001 | 0.002 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.002 | 0.004 |
| Insufficient payload (model declined to judge) | 0.009 | 0.002 |
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".