Phase II study of maintenance therapy with temsirolimus (TEM) after response to first-line docetaxel (TAX) chemotherapy in castration-resistant prostate cancer (CRPC).
Bibliographic record
Abstract
160 Background: TAX is the standard first-line chemotherapy for CRPC. However, a number of questions remain regarding the optimal use of TAX following maximal response. Aside from intermittent TAX, maintenance therapy with well-tolerated agents such as the mTOR inhibitor TEM could be one strategy to prolong treatment response and the chemotherapy-free interval, without significantly compromising quality of life. In fact, the mTOR pathway is involved in many aspects of CRPC, and mTOR inhibitors have demonstrated significant anti-CRPC activity in preclinical testing. Methods: CRPC pts eligible for this single-arm, multicenter phase II trial must have received between 6 to 8 cycles of first-line TAX (75 mg/m2 q3wks) with documented treatment response by PSA (>50% decline from baseline) or RECIST criteria. 30 pts will be enrolled and administered weekly TEM (25 mg iv × 4/cycle). The primary endpoint is time to treatment failure (TTF, by RECIST or symptomatic progression). Secondary endpoints include safety (NCI-CTCAE v3.0), quality of life (FACT-P, PPI), changes in PSA doubling time and time to PSA progression, objective tumor response rate (RECIST), and overall survival. We will also study correlative endpoints using plasma and peripheral blood mononuclear cells (i.e., markers of mTOR inhibition, of antiangiogenic TEM effects and of intratumoral hypoxia/acidosis, the latter as potential predictive markers). Results: 10 pts have been enrolled to date: mean age 68 (range 52-80), prior definitive local therapy (7)—radiation (6), prostatectomy (1), mean PSA at entry 99.28 (2.3- 380.7), ECOG 0 (4) or 1 (6), prior cycles of TAX 6 (6) or 8 (4), sites of metastasis—bone (8), lymph nodes (4), visceral (3). 6 pts have been discontinued due to treatment failure after a mean of 5.3±1.9 cycles (range 3-8) - RECIST (1), symptomatic (2), combined (3). 4 pts are on cycle 1-2-8-9, respectively. TEM has been generally well tolerated without unexpected side-effects, but may have contributed to worsening lymphedema in 1 pt. Conclusions: TEM maintenance therapy in CRPC pts that have responded to first-line TAX is well tolerated and appears to result in meaningful TTF. 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 | 0.002 | 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 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.002 | 0.000 |
| Research integrity | 0.002 | 0.005 |
| Insufficient payload (model declined to judge) | 0.004 | 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".