Paclitaxel
| Evidence Level: L1 | Predicted Indications: 10 |
Table of Contents
Paclitaxel: From an Unspecified Original Indication to Female Breast Carcinoma
One-Sentence Summary
Paclitaxel is a taxane-class chemotherapy agent; however, this evidence pack does not contain its documented original indication (data gap) or EU marketing/label data. The TxGNN model’s top prediction is Female Breast Carcinoma, supported by more than 50 clinical trials and 20 publications — but the evidence pack’s own mechanistic analysis flags this as very likely a re-confirmation of Paclitaxel’s already-established standard indication, not a genuine repurposing discovery.
Quick Overview
| Item | Content |
|---|---|
| Original Indication | Not available (no EMA license records in this evidence pack) |
| Predicted New Indication | Female Breast Carcinoma |
| TxGNN Prediction Score | 99.995% |
| Evidence Level | L1 |
| EU Market Status | ✗ Not Marketed |
| Number of Authorizations | 0 |
| Recommended Decision | Hold |
Why is This Prediction Reasonable?
Detailed DrugBank mechanism-of-action data is marked as a data gap in this evidence pack. Based on the mechanistic rationale attached to the top prediction, Paclitaxel acts as a microtubule-stabilizing agent: it binds β-tubulin and inhibits microtubule depolymerization, arresting cells in the M phase of mitosis. This produces cytotoxic effects preferentially in rapidly proliferating cells, including breast carcinoma cells.
However, a critical caveat must be flagged: the evidence pack’s own rationale for this candidate states explicitly that this is not actually a novel repurposing signal. Paclitaxel is a globally established standard chemotherapy for breast cancer, and the “prediction” appears here only because the original_indications field in the source drug record was empty (a data pipeline gap), causing an already-known indication to be scored as if it were new. The same issue affects several other top-ranked candidates in this evidence pack (e.g., ER-negative breast cancer, ER-positive breast cancer, hormone-resistant breast carcinoma), which are simply clinical subtypes/contexts of the same established indication rather than independent repurposing opportunities.
Because the mechanism (microtubule inhibition via β-tubulin binding) does not depend on hormone-receptor status, it mechanistically explains efficacy across ER-positive, ER-negative, and hormone-resistant breast cancer subtypes alike — which is consistent with why the model scores these subtypes so highly. This strengthens the plausibility of the biology, but does not change the conclusion that this is a known-indication reconfirmation rather than a new discovery requiring separate regulatory pursuit.
Clinical Trial Evidence
| Trial Number | Phase | Status | Enrollment | Key Findings |
|---|---|---|---|---|
| NCT00991263 | N/A (translational) | Completed | 3,677 | Landmark analysis of breast cancer intrinsic subtypes and paclitaxel benefit, using CALGB 9344/9741 trial samples — foundational evidence for paclitaxel’s role in adjuvant therapy. |
| NCT07327021 | Phase 2 | Recruiting | 54 | MRI-guided neoadjuvant de-escalation trial in stage II–III triple-negative breast cancer (TNBC). |
| NCT00272987 | Phase 3 | Terminated | 63 | Double-blind RCT of paclitaxel + trastuzumab ± lapatinib in ErbB2-overexpressing metastatic breast cancer; stopped early. |
| NCT01275677 | Phase 3 | Completed | 3,270 | Adjuvant chemotherapy (incl. weekly paclitaxel) alone vs. plus trastuzumab in node-positive/high-risk HER2-low breast cancer. |
| NCT00433420 | Phase 3 | Active, not recruiting | 2,000 | EC→paclitaxel vs. FEC→paclitaxel (q3w or q2w with pegfilgrastim support) in node-positive breast cancer. |
| NCT00003088 | Phase 3 | Completed | 2,005 | Sequential doxorubicin/paclitaxel/cyclophosphamide vs. concurrent AC→paclitaxel at different intervals in node-positive stage II/IIIA breast cancer. |
| NCT02125344 | Phase 3 | Completed | 961 | GeparOcto: two dose-dense, dose-intensified neoadjuvant regimens (incl. paclitaxel) in high-risk early breast cancer. |
| NCT01901146 | Phase 3 | Completed | 725 | Double-blind biosimilar comparison (ABP 980 vs. trastuzumab, paclitaxel backbone) in HER2-positive early breast cancer. |
| NCT00915018 | Phase 2 | Completed | 479 | Neratinib + paclitaxel vs. trastuzumab + paclitaxel as first-line therapy for ErbB2-positive metastatic breast cancer. |
| NCT00553358 | Phase 3 | Completed | 455 | Neo-ALTTO: neoadjuvant lapatinib, trastuzumab, and their combination, all plus paclitaxel, in HER2-positive primary breast cancer. |
Literature Evidence
| PMID | Year | Type | Journal | Key Findings |
|---|---|---|---|---|
| 31783552 | 2019 | Review | Biomolecules | Comprehensive review of paclitaxel’s mechanistic and clinical effects in breast cancer, including resistance mechanisms. |
| 11147586 | 2000 | Cohort/Comparative | Cancer | Phase II trial: doxorubicin + paclitaxel efficacy/toxicity in advanced breast carcinoma; role of prior adjuvant anthracycline exposure. |
| 9282422 | 1997 | Review | Drug and Therapeutics Bulletin | Early review documenting extension of taxane licensure to first-line breast and ovarian cancer treatment. |
| 39317691 | 2024 | — | Chem Biol Drug Des | Explores paclitaxel combination therapies against breast carcinoma and identifies in vivo biomarkers using patient-derived models. |
| 39009452 | 2024 | — | J Immunother Cancer | Paclitaxel’s effect on tumor-associated macrophages to enhance PD-1 blockade efficacy in TNBC. |
| 24823476 | 2014 | — | Nature Communications | Identifies TEKT4 germline variants enriched in breast cancer resistant to paclitaxel. |
| 32461977 | 2020 | — | BioMed Research International | Real-world study: neoadjuvant epirubicin/cyclophosphamide + weekly paclitaxel + trastuzumab in HER2+ breast carcinoma. |
| 17272681 | 2007 | — | Molecular Pharmacology | Mechanistic study on reversing stathmin-mediated resistance to paclitaxel and vinblastine in breast carcinoma cells. |
| 9164198 | 1997 | — | J Clin Oncol | ECOG Phase II trial of biweekly paclitaxel + cisplatin in advanced breast carcinoma. |
| 11745249 | 2001 | — | Cancer | Role of paclitaxel in multimodality treatment for inflammatory breast carcinoma. |
EU Market Information
No EMA marketing authorization records are present in this evidence pack (taiwan_regulatory.total_licenses = 0, market status: Not Marketed). No product-level authorization table can be generated.
Cytotoxicity
Paclitaxel is a conventional cytotoxic chemotherapy agent (taxane class).
| Item | Content |
|---|---|
| Cytotoxicity Classification | Conventional cytotoxic (Taxane class — microtubule-stabilizing agent, β-tubulin binding) |
| Myelosuppression Risk | Please refer to the SmPC warnings and precautions |
| Emetogenicity Classification | Please refer to the SmPC warnings and precautions |
| Monitoring Items | Please refer to the SmPC warnings and precautions |
| Handling Protection | Please refer to the SmPC warnings and precautions |
Note: Detailed toxicity/monitoring data are subject to a Blocking data gap in this evidence pack (missing TFDA/EMA product label) and cannot be sourced beyond the general drug-class classification above.
Safety Considerations
Please refer to the SmPC for safety information.
Conclusion and Next Steps
Decision: Hold
Rationale:
- The evidence pack flags a Blocking data gap (missing TFDA/EMA label — warnings, contraindications, DDI), which by definition prevents completion of the S1 safety evaluation regardless of clinical efficacy evidence.
- The evidence pack’s own mechanistic rationale indicates the top-ranked candidate (and several related subtype candidates: ER-negative, ER-positive, and hormone-resistant breast cancer) most likely represents Paclitaxel’s already-established standard indication, misclassified as a “new prediction” due to a missing
original_indicationsfield — not a genuine repurposing discovery. - The drug currently has no EU marketing authorization on record in this dataset (0 licenses), so no regulatory pathway context is available for a “Go” decision.
To proceed, the following is needed:
- Obtain the official TFDA/EMA-approved product label (warnings, contraindications, drug interactions) to complete the S1 safety evaluation.
- Retrieve the formal DrugBank mechanism-of-action record to replace the current data gap.
- Re-verify the
original_indicationsfield against an authoritative source; if Paclitaxel’s approved breast cancer indication is confirmed, reclassify this candidate as “known indication” rather than a repurposing opportunity, and re-run TxGNN scoring excluding already-approved indications. - Prioritize evaluation of the genuinely novel, evidence-free candidates in this pack (e.g., parameningeal embryonal rhabdomyosarcoma, botryoid-type embryonal rhabdomyosarcoma of the vagina — both L5, zero trials/literature) only after preclinical mechanistic validation, given they currently have no supporting evidence.
Disclaimer
This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.