Paclitaxel

證據等級: L5

預測適應症: 10 個

Paclitaxel: From Antineoplastic Chemotherapy to Female Breast Carcinoma

One-Sentence Summary

Paclitaxel is a taxane-class cytotoxic chemotherapy agent with a long history of use across multiple solid tumour types. The TxGNN model’s top-ranked prediction — Female Breast Carcinoma — is supported by an unusually strong evidence base of 50+ clinical trials (including large Phase 3 randomised trials) and 20 publications, though the evidence indicates this is a confirmation of paclitaxel’s already well-established role in breast cancer treatment rather than a genuinely novel repurposing hypothesis.

Quick Overview

Item	Content
Original Indication	Not documented in this evidence pack (drug-level indication data gap); Paclitaxel is internationally recognised as a taxane-class antineoplastic agent used across multiple solid tumours
Predicted New Indication	Female Breast Carcinoma
TxGNN Prediction Score	99.99%
Evidence Level	L1
Australia Market Status	Not marketed (per this evidence pack)
Number of ARTG Entries	0
Recommended Decision	Proceed with Guardrails

Why is This Prediction Reasonable?

Currently, detailed mechanism of action data for this drug record is not available (data gap). Based on established pharmacological knowledge, Paclitaxel is a taxane that binds to and stabilises tubulin polymers, preventing microtubule depolymerisation. This locks cells in metaphase, blocking mitotic progression and triggering apoptosis — an effect that is most pronounced in rapidly dividing cell populations such as breast carcinoma cells.

While this evidence pack does not record a specific “original indication” for the drug, the evidence trail for the predicted indication itself tells an important story: the volume, phase and completeness of the clinical trial record (including the pivotal CALGB 9344 trial establishing adjuvant benefit in node-positive breast cancer) indicate that paclitaxel’s use in breast carcinoma is already an established, guideline-endorsed practice internationally, rather than a new hypothesis generated purely from knowledge-graph inference. The model’s other top-ranked candidates for this drug — estrogen-receptor negative breast cancer, hormone-resistant breast carcinoma, and estrogen-receptor positive breast cancer — reinforce this pattern, all scoring similarly highly and drawing on overlapping trial evidence.

Mechanistically, this consistency makes sense: paclitaxel’s cytotoxic, antimitotic action is independent of hormone receptor (ER/PR) or HER2 status, which is why it retains efficacy across all major molecular subtypes of breast cancer — from hormone receptor-positive disease requiring chemotherapy, through to triple-negative and HER2-overexpressing tumours. For a pharmacist reviewing this record, the key takeaway is that this “prediction” reflects the confirmation of pre-existing, high-quality clinical evidence rather than an unproven repurposing signal.

Clinical Trial Evidence

Trial Number	Phase	Status	Enrolment	Key Findings
NCT00991263	N/A (correlative/translational)	Completed	3,677	CALGB 9344/9741 tissue-based analysis identifying which intrinsic breast cancer subtypes derive benefit from adjuvant paclitaxel — a pivotal, practice-informing dataset
NCT00272987	Phase 3	Terminated	63	Randomised, double-blind, placebo-controlled trial of paclitaxel + trastuzumab ± lapatinib in HER2-overexpressing metastatic breast cancer
NCT01275677	Phase 3	Completed	3,270	Adjuvant chemotherapy (docetaxel/cyclophosphamide, or doxorubicin/cyclophosphamide followed by weekly paclitaxel) ± trastuzumab in node-positive/high-risk HER2-low breast cancer
NCT00003088	Phase 3	Completed	2,005	Sequential vs concurrent doxorubicin, paclitaxel and cyclophosphamide at different dosing intervals for node-positive Stage II/IIIA breast cancer
NCT02125344	Phase 3	Completed	961	GeparOcto: dose-dense, dose-intensified paclitaxel-containing regimens as neoadjuvant treatment for high-risk early breast cancer
NCT00433420	Phase 3	Active, not recruiting	2,000	EC→paclitaxel vs FEC→paclitaxel (2- vs 3-weekly, pegfilgrastim-supported) for node-positive breast cancer
NCT04158362	Phase 3	Active, not recruiting	180	AMBRE: standard chemotherapy vs endocrine therapy + abemaciclib as initial treatment for ER+/HER2- metastatic breast cancer with high visceral burden
NCT00709761	Phase 2	Completed	60	Weekly nab-paclitaxel + lapatinib in HER2-overexpressing metastatic breast cancer
NCT04771871	Phase 2	Unknown	42	Treatment response and microRNA profiling in triple-negative breast cancer patients receiving standard (paclitaxel-based) chemotherapy
NCT05238922	Phase 1	Recruiting	604	INCB123667 as monotherapy and in combination with anticancer therapies (including paclitaxel-based regimens) in advanced solid tumours, including breast cancer

No ANZCTR-registered trials were identified in this evidence pack.

Literature Evidence

PMID	Year	Type	Journal	Key Findings
11147586	2000	Cohort/Clinical Study	Cancer	Phase II multicentre trial of doxorubicin + paclitaxel in metastatic breast carcinoma; efficacy influenced by prior adjuvant anthracycline exposure
32461977	2020	Cohort/Clinical Study	BioMed Research International	Real-world evaluation of neoadjuvant epirubicin/cyclophosphamide + weekly paclitaxel-trastuzumab in HER2-positive breast carcinoma
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 independent review confirming paclitaxel/docetaxel efficacy in breast and ovarian cancer
24823476	2014	Genetic Association Study	Nature Communications	TEKT4 germline variants enriched in breast tumours resistant to paclitaxel, informing predictive biomarker research
39317691	2024	Preclinical/Mechanistic	Chemical Biology & Drug Design	Paclitaxel combination therapy potential and in vivo biomarkers in breast carcinoma models
31515668	2019	Preclinical/Mechanistic	Cancer Chemotherapy and Pharmacology	SRSF3 downregulation sensitises breast cancer (and oral squamous cell carcinoma) cells to paclitaxel
39009452	2024	Preclinical/Mechanistic	Journal for ImmunoTherapy of Cancer	Paclitaxel’s effect on tumour-associated macrophages enhancing PD-1 blockade activity in breast cancer
36964413	2023	Preclinical/Mechanistic	Human Cell	TIPE2 sensitises breast cancer cells to paclitaxel by suppressing drug-induced autophagy and cancer stem cell properties
20665703	2011	Preclinical/In vitro	Journal of Cellular Physiology	ZD6474 (a dual EGFR/VEGFR inhibitor) enhances paclitaxel’s antiproliferative and apoptotic effects in breast carcinoma cells

Australia Market Information

According to this evidence pack, Paclitaxel currently has no ARTG entries recorded and is listed as not marketed in Australia (total licenses: 0). Given that paclitaxel is a long-established, internationally used chemotherapy agent, this market status should be independently verified against the current TGA ARTG database before any regulatory or clinical decision is made, as it appears inconsistent with paclitaxel’s well-known global availability.

Cytotoxicity

Paclitaxel is a conventional cytotoxic chemotherapy agent (taxane class), meeting the antineoplastic classification criteria based on its established pharmacological class and its use exclusively against malignant solid tumours across all candidate indications in this evidence pack.

Item	Content
Cytotoxicity Classification	Conventional cytotoxic (Taxane class — microtubule-stabilising antimitotic agent)
Myelosuppression Risk	High — neutropenia is the dose-limiting toxicity for paclitaxel; thrombocytopenia and anaemia are also commonly reported, particularly with dose-dense regimens
Emetogenicity Classification	Low to moderate (per standard oncology emetogenic-risk classifications for IV taxane monotherapy)
Monitoring Items	Full blood count with differential (neutrophil nadir), liver function tests, peripheral neuropathy assessment, and observation for hypersensitivity reactions during infusion
Handling Protection	Yes — standard cytotoxic drug handling precautions apply (personal protective equipment, closed-system transfer devices, spill management)

Note: specific toxicity/monitoring data was not available in this evidence pack’s safety fields; the above reflects established pharmacological class knowledge for taxanes. Please cross-check against the TGA-approved Product Information once available.

Safety Considerations

Please refer to the TGA-approved Product Information (PI) for safety information. No key warnings, contraindications, or drug-drug interaction data were available in this evidence pack, and this represents a Blocking data gap (DG001) that prevents completion of the initial safety assessment (S1) for this candidate.

Conclusion and Next Steps

Decision: Proceed with Guardrails

Rationale: The clinical trial and literature evidence for paclitaxel in female breast carcinoma is extensive and high-quality (L1), including pivotal Phase 3 trials such as CALGB 9344. However, this evidence largely confirms an already well-established global indication rather than validating a novel repurposing hypothesis, and critical Australian regulatory and safety data (TGA PI, ARTG status, mechanism of action) are currently missing from this record.

To proceed, the following is needed:

Obtain the TGA-approved Product Information (PI) for Paclitaxel to complete the safety pre-assessment (S1) — currently a Blocking data gap (DG001)
Verify the drug’s actual ARTG registration status in Australia, as “not marketed / 0 entries” appears inconsistent with paclitaxel’s well-documented global clinical use
Source formal mechanism of action (MOA) documentation from DrugBank or equivalent to complete the mechanistic-relevance analysis (DG002)
Clarify with clinical/regulatory stakeholders whether this candidate should be handled under a standard registration/label-extension pathway rather than a novel drug-repurposing pathway, given that breast carcinoma is an established use of paclitaxel internationally
Disclaimer

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