Docetaxel
| 證據等級: L5 | 預測適應症: 10 個 |
目錄
Docetaxel: From Cytotoxic Chemotherapy to Female Breast Carcinoma
One-Sentence Summary
Docetaxel is a taxane-class antineoplastic (cytotoxic chemotherapy) agent used broadly across solid-tumor oncology; a documented original-indication record was not available for this product in the current evidence pack (Taiwan license and mechanism-of-action data are both flagged as gaps). The TxGNN model’s top-ranked prediction — Female Breast Carcinoma — is supported by 50 clinical trials and 20 publications, though the evidence itself indicates this is already a globally established, approved use of docetaxel rather than a genuinely novel repurposing signal.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not on file — no Taiwan license record found in this evidence pack (see Data Gaps DG001/DG002) |
| Predicted New Indication | Female Breast Carcinoma |
| TxGNN Prediction Score | 99.90% |
| Evidence Level | L1 |
| US Market Status | ✗ Not Marketed (0 licenses on record in this evidence pack) |
| Number of NDAs | 0 |
| Recommended Decision | Proceed with Guardrails |
Why is This Prediction Reasonable?
The formal drug-level mechanism-of-action field for docetaxel is a documented data gap (DG002, High severity) in this evidence pack. However, the candidate-level analysis attached to this prediction does supply mechanistic detail: docetaxel is a taxane that binds and stabilizes microtubules, blocking their depolymerization. This arrests rapidly dividing cells — including breast cancer cells — in the G2/M phase of the cell cycle and induces apoptosis, consistent with well-established taxane pharmacology (cf. PMID 7595719, describing docetaxel as an “antineoplastic taxoid”).
Because no Taiwan-approved indication was found on file (market status: Not Marketed, 0 licenses), a direct “original → new indication” comparison cannot be constructed from local regulatory records. Importantly, the evidence pack’s own rationale for this candidate is explicit that female breast carcinoma is not actually a novel finding: docetaxel is already a globally approved, standard-of-care chemotherapy agent for breast cancer, which is precisely why the supporting literature base is so mature (multiple completed Phase 3 RCTs). In this instance, the TxGNN signal functions more as a confirmation of known pharmacology than as a genuine repurposing discovery.
Mechanistically, microtubule-stabilizing, cell-cycle-arrest cytotoxicity is broadly applicable to any rapidly proliferating solid tumor, which explains both the very high TxGNN score (99.90%) and the depth of independent clinical evidence — including at least three completed Phase 3 RCTs among the trials below — specifically supporting docetaxel-based regimens in breast carcinoma.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00841828 | Phase 2 | Completed | 102 | RCT comparing EC+Docetaxel+Trastuzumab vs. EC+Docetaxel+Lapatinib in HER2+ resectable/locally advanced breast cancer |
| NCT02413320 | Phase 2 | Completed | 101 | Neoadjuvant carboplatin+docetaxel vs. carboplatin+paclitaxel in Stage I-III triple-negative breast cancer |
| NCT00941330 | Phase 2 | Completed | 31 | Pre-operative docetaxel-cyclophosphamide vs. exemestane in hormone receptor-positive breast cancer |
| NCT03252431 | Phase 3 | Completed | 393 | F-627 vs. Neulasta for neutropenia prevention in docetaxel-based chemotherapy for Stage I-III breast cancer (confirms docetaxel as standard chemo backbone) |
| NCT00003519 | Phase 3 | Completed | 2,778 | Adjuvant Adriamycin/Taxotere vs. Adriamycin/Cytoxan in node-positive or high-risk node-negative breast cancer |
| NCT00017095 | Phase 3 | Completed | 1,856 | Randomized taxane vs. non-taxane regimen with p53 predictive-value translational research in locally advanced/operable breast cancer |
| NCT00408408 | Phase 3 | Unknown | 1,206 | Neoadjuvant docetaxel ± capecitabine/gemcitabine ± bevacizumab before AC, evaluating pathologic complete response |
| NCT00545688 | Phase 2 | Completed | 417 | 4-arm neoadjuvant study of Herceptin/docetaxel/pertuzumab combinations in HER2+ breast cancer |
| NCT05189067 | Phase 2/3 | Unknown | 190 | Adjuvant paclitaxel+trastuzumab vs. docetaxel+trastuzumab in Stage I HER2+ breast cancer |
| NCT00629278 (SHORT-HER) | Phase 3 | Unknown | 2,500 | Two adjuvant chemotherapy regimens plus 3 vs. 12 months trastuzumab in HER2+ breast cancer |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 28398846 | 2017 | RCT (ABC Trials) | J Clin Oncol | Docetaxel/cyclophosphamide (TC) vs. anthracycline-taxane regimens in early breast cancer adjuvant therapy |
| 12599222 | 2003 | Clinical Trial | Cancer | Capecitabine + docetaxel + epirubicin (TEX) as first-line therapy in advanced breast carcinoma |
| 15161988 | 2004 | Review | The Oncologist | Review of docetaxel and paclitaxel roles across metastatic, adjuvant, and neoadjuvant breast cancer therapy |
| 27997437 | 2017 | Cohort | Anti-Cancer Drugs | Association between adjuvant docetaxel-based chemotherapy and breast cancer-related lymphedema |
| 7595719 | 1995 | Review | J Clin Oncol | Foundational review of docetaxel’s preclinical and clinical profile as an antineoplastic taxoid |
| 9364543 | 1997 | Review | Oncology (Williston Park) | Combination docetaxel/vinorelbine activity in metastatic breast cancer and NSCLC |
| 19856651 | 2009 | Dose-finding study | Tumori | Docetaxel + gemcitabine dose-finding study in anthracycline-pretreated metastatic breast carcinoma |
| 26874836 | 2017 | Clinical study | Breast Cancer (Tokyo) | Docetaxel, cyclophosphamide, and trastuzumab as neoadjuvant chemotherapy for HER2+ breast cancer |
| 16020974 | 2005 | Phase 2 | Oncology | Weekly docetaxel + gemcitabine as first-line treatment for metastatic breast cancer |
| 15858439 | 2005 | Phase 2 (interim) | Breast Cancer (Tokyo) | CEF followed by docetaxel as preoperative chemotherapy for early-stage breast carcinoma |
US Market Information
No market authorization license was found for this product in the current evidence pack. The Taiwan regulatory query (tfda) executed successfully but returned zero license records (total_licenses = 0, market_status = "Not Marketed"). Consequently, no authorization number, product name, dosage form, or approved-indication text can be reported at this time; this should be confirmed directly against TFDA records before any market-facing decision is made.
Cytotoxicity
Docetaxel is a taxane-class cytotoxic chemotherapy agent (criteria met: literature explicitly describes it as an “antineoplastic taxoid,” and it belongs to the recognized taxane chemotherapy class).
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (taxane class — microtubule-stabilizing agent) |
| Myelosuppression Risk | High — the evidence base includes multiple trials specifically evaluating G-CSF/pegfilgrastim or biosimilar filgrastim support and neutropenic sepsis rates in docetaxel-treated patients (e.g., NCT03252431, retrospective UK sepsis review) |
| Emetogenicity Classification | Low to Moderate (typical of taxane-class agents) |
| Monitoring Items | CBC with differential (neutrophil count), liver function (docetaxel is predominantly hepatobiliary-excreted per PK literature in the pack), fluid retention/edema and lymphedema surveillance (per PMID 27997437), peripheral neuropathy assessment |
| Handling Protection | Must follow institutional cytotoxic/hazardous drug handling and disposal regulations |
Formal DrugBank toxicity monographs and the TFDA package insert were not retrieved in this evidence pack (see Data Gaps below); the items above are derived from the clinical trial and literature evidence on file. Please refer to the package insert warnings and precautions for complete prescribing information.
Safety Considerations
Please refer to the package insert for safety information. Key warnings, contraindications, and drug-drug interaction data were not available in this evidence pack (DDI query status: not found).
Conclusion and Next Steps
Decision: Proceed with Guardrails
Rationale:
- The evidence for docetaxel in female breast carcinoma is exceptionally mature (L1: multiple completed Phase 3 RCTs, 50 total trials, 20 publications), but per the evidence pack’s own rationale this largely confirms an already globally approved, standard-of-care use rather than a novel repurposing signal.
- A drug-level Blocking data gap exists (DG001: TFDA package insert warnings/contraindications not retrieved) — per the evidence pack metadata, this gap by itself prevents the candidate from entering the S1 safety pre-screening stage, independent of how strong the efficacy evidence is for any single indication.
To proceed, the following is needed:
- Retrieve the TFDA package insert (warnings/contraindications) — Blocking gap (DG001)
- Retrieve a formal DrugBank mechanism-of-action record — High-priority gap (DG002)
- Directly confirm Taiwan market/license status, since this evidence pack found zero licenses on file
- Clarify why female breast carcinoma is being scored as a “predicted new indication” when the supporting rationale states it is already an approved standard use — this may warrant a candidate-selection/mapping review
- Consider follow-up on the other candidates in this multi-indication screen with genuinely off-label signal and moderate (L2) evidence: Ewing sarcoma (rank 2, GEMDOX-type docetaxel+gemcitabine regimens) and rhabdomyosarcoma (rank 8, similar sarcoma salvage regimens)
- Manually re-verify the disease-label mapping for small cell lung carcinoma (rank 4) and primary pulmonary lymphoma (rank 5) — the cited trials/literature for both predominantly concern NSCLC/ALK-positive lung cancer rather than the labeled disease, per data-quality flags already noted in the evidence pack itself
- Treat the remaining low-evidence candidates (well-differentiated fetal adenocarcinoma of the lung, botryoid-type embryonal rhabdomyosarcoma of the vagina, pulmonary blastoma, embryonal extrahepatic bile duct rhabdomyosarcoma, parameningeal embryonal rhabdomyosarcoma — all L4/L5, decision “Hold”) as research hypotheses only, not near-term candidates
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.