Paclitaxel

證據等級: L5

預測適應症: 10 個

Paclitaxel: From Ovarian/Lung Cancer to Female Breast Carcinoma

One-Sentence Summary

Paclitaxel is a taxane-class cytotoxic chemotherapy agent with broad international approval across solid tumors (e.g., ovarian and non-small cell lung cancer); Danish-specific original-indication text was not available in this evidence pack. The TxGNN model predicts continued/renewed relevance for Female Breast Carcinoma, supported by an unusually large body of existing evidence — 50 clinical trials (including multiple completed Phase 3 RCTs) and 20 publications were retrieved, though this largely reflects paclitaxel’s already-established role in breast cancer rather than a novel repurposing signal.

Quick Overview

Item	Content
Original Indication	Not available from Danish licence records (0 licences on file); internationally approved for ovarian cancer, non-small cell lung cancer, and other solid tumors
Predicted New Indication	Female Breast Carcinoma
TxGNN Prediction Score	99.995%
Evidence Level	L1 (≥2 completed Phase 3 RCTs identified)
Denmark Market Status	Not marketed (未上市)
Number of Marketing Authorisations	0
Recommended Decision	Hold

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data is not available from DrugBank for this evidence pack (flagged as a High-severity data gap, DG002). Based on generally known pharmacology, Paclitaxel is a taxane-class agent that stabilizes microtubules and blocks mitotic spindle disassembly, driving apoptosis in rapidly dividing cells — a mechanism broadly applicable across proliferative solid tumors.

Paclitaxel’s efficacy in ovarian and lung cancer, both high-proliferation solid tumors, is mechanistically consistent with activity against breast carcinoma, which shares similar dependence on cell-cycle progression and microtubule dynamics for tumor growth.

Importantly, the volume and maturity of the retrieved evidence (multiple completed Phase 3 randomized trials spanning three decades, including adjuvant, neoadjuvant, and metastatic settings) indicate that paclitaxel is already an established standard-of-care agent in breast cancer treatment internationally. This TxGNN prediction therefore largely reconfirms known clinical practice rather than surfacing a genuinely novel repurposing opportunity — a point that should inform how “new indication” is interpreted in this specific case.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrollment	Key Findings
NCT00005970	Phase 3	Completed	3,436	AC followed by weekly paclitaxel ± trastuzumab as adjuvant therapy in HER2-overexpressing or high-risk node-positive/negative breast cancer
NCT00561119	Phase 3	Completed	326	Maintenance vs. observation after 6 cycles of gemcitabine + paclitaxel as 1st-line therapy in metastatic/recurrent breast cancer
NCT00004125	Phase 3	Completed	N/A	AC followed by paclitaxel or docetaxel, weekly vs. every 3 weeks, in axillary node-positive breast cancer
NCT00002953	Phase 3	Completed	704	Epirubicin + cyclophosphamide vs. epirubicin + paclitaxel in metastatic breast cancer
NCT01426880	Phase 2/3	Completed	595	Addition of carboplatin to neoadjuvant anthracycline-taxane-trastuzumab therapy in triple-negative and HER2+ early breast cancer
NCT03289819	Phase 2	Completed	53	Neoadjuvant pembrolizumab + nab-paclitaxel followed by pembrolizumab + EC in triple-negative breast cancer
NCT05296798	Phase 3	Active, not recruiting	922	Giredestrant + Phesgo vs. Phesgo after induction with Phesgo + taxane in HER2+/ER+ advanced breast cancer
NCT02280252	Phase 2	Completed	69	Concurrent paclitaxel and radiation in locally advanced breast cancer, multiethnic cohort
NCT01366144	Phase 1	Active, not recruiting	94	Veliparib + carboplatin + paclitaxel in solid tumor patients with hepatic/renal dysfunction
NCT05189535	Phase 2/3	Completed	66	Pentoxifylline for prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients

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
9282422	1997	Review	Drug and Therapeutics Bulletin	Early regulatory review of paclitaxel and docetaxel use in breast and ovarian cancer
9164198	1997	Phase II trial	J Clin Oncol	ECOG study of biweekly paclitaxel + cisplatin in advanced breast carcinoma
11147586	2000	Phase II trial	Cancer	Doxorubicin + paclitaxel combination in advanced metastatic breast carcinoma
32461977	2020	Real-world study	BioMed Research International	Neoadjuvant EC + weekly paclitaxel + trastuzumab in HER2-positive breast carcinoma
24068539	2013	Phase I-II trial	Breast Cancer Res Treat	Tipifarnib + sequential weekly paclitaxel and AC in inflammatory and ER-positive breast carcinoma
11745249	2001	Case series	Cancer	Paclitaxel in multimodality treatment of inflammatory breast carcinoma
39317691	2024	Preclinical	Chemical Biology & Drug Design	Paclitaxel combination therapeutic potential against breast carcinoma with in vivo biomarker identification
17272681	2007	Preclinical	Molecular Pharmacology	Mechanistic study of stathmin-mediated resistance reversal to paclitaxel in breast carcinoma cells
9821299	1998	Preclinical	Folia Microbiologica	Antitumor activity of paclitaxel + epirubicin combination in ER-positive human breast carcinoma model

Denmark Market Information

No marketing authorisation records were returned for Paclitaxel in this evidence pack (total_licenses: 0, market_status: 未上市/Not marketed). This is notable given paclitaxel’s broad international generic availability, and should be treated as a data-collection gap requiring verification rather than confirmed absence from the Danish market.

Cytotoxicity

Paclitaxel is a well-established cytotoxic antineoplastic (taxane class), so this section applies.

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (taxane / microtubule-stabilizing agent)
Myelosuppression Risk	Please refer to the Summary of Product Characteristics (SmPC) — no toxicity data was returned in this evidence pack
Emetogenicity Classification	Please refer to the Summary of Product Characteristics (SmPC) — no toxicity data was returned in this evidence pack
Monitoring Items	Please refer to the Summary of Product Characteristics (SmPC) warnings and precautions
Handling Protection	Cytotoxic drug handling precautions are expected to apply as a class-standard requirement for antineoplastic infusion agents; specific protocol should follow SmPC/local guidance

Safety Considerations

Please refer to the approved Summary of Product Characteristics (SmPC) for safety information.

Conclusion and Next Steps

Decision: Hold

Rationale:

Existing clinical evidence for paclitaxel in breast carcinoma is strong (Evidence Level L1, multiple completed Phase 3 RCTs), but this reflects already-established international standard-of-care use rather than a novel repurposing signal.
A Blocking-severity data gap (DG001: TFDA/SmPC warnings and contraindications unavailable) prevents any safety initial assessment (S1) from proceeding, regardless of efficacy evidence strength.

To proceed, the following is needed:

Obtain TFDA/Danish SmPC label text (warnings, contraindications) — resolves Blocking gap DG001
Retrieve confirmed mechanism of action data from DrugBank — resolves High-severity gap DG002
Verify actual Danish/EU marketing authorisation status, since the current record of 0 licences is inconsistent with paclitaxel’s known wide generic availability and likely reflects incomplete data collection
Clarify whether “female breast carcinoma” should be treated as a genuine repurposing candidate or reclassified as confirmatory evidence of existing standard-of-care use
Disclaimer

This content is for research purposes only and does not constitute medical advice. Clinical validation is required before any clinical application.