The timing of docetaxel initiation in metastatic castrate sensitive prostate cancer and the rate of chemotherapy induced toxicity.
Bibliographic record
Abstract
e17005 Background: Docetaxel is currently used to treat both metastatic castrate resistant prostate cancer (mCRPC) and recently metastatic castrate sensitive prostate cancer (mCSPC). The CHAARTED protocol for mCSPC initiated chemotherapy within four months of the start of androgen deprivation therapy (ADT). There is evidence suggesting that docetaxel pharmacokinetics is affected by ADT which is attributed to change in liver metabolism induced by castration. This may explain the difference in docetaxel toxicity between patients (pts) with mCSPC and mCRPC. In this retrospective analysis we will assess whether initiating docetaxel treatment in close proximity to start of ADT therapy for mCSPC is associated with more treatment related toxicity. Methods: We identified all pts with mCSPC treated at The Ottawa Hospital Cancer Center with docetaxel chemotherapy between June 2014 - September 2017. For each patient we calculated the time to chemotherapy (TTC) interval between the start of ADT and the 1st cycle of docetaxel. We checked for an association between TTC and febrile neutropenia (FN) toxicity induced treatment delay or discontinuation, and toxicity induced dose reduction. Results: Eighty three pts were identified. The median TTC was 67 days (range 3-189). Twenty three pts (27.7%) experienced FN. Docetaxel toxicity resulted in 8 patients (9.6%) had their treatment delayed, 30 patients (36.1%) had their dose reduced and 18 (21.6%) had their treatment discontinued before completing the scheduled 6 cycles. No correlation was found between the TTC and FN (P = 0.99), docetaxel dose reduction (P = 0.95), treatment delay (P = 0.06) and treatment discontinuation (P = 0.88). Conclusions: No correlation was found between the timing of docetaxel treatment start and the rate of treatment related toxicity. Therefore, there is no indication for upfront chemotherapy delay from start of ADT unless the patient’s overall condition is not well enough and it is anticipated that ADT treatment may improve their condition. However, the rate of FN (27.7%) is much higher than expected, regardless of TTC and prophylactic granulocyte colony-stimulating factor may be considered in a real world population.
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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 | 0.005 |
| 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 | 0.000 |
| 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".