Paclitaxel CAS：33069-62-4
Mechanism of Action: This therapeutic agent specifically attaches to assembled microtubules, promoting their stability and thereby interfering with normal cell division processes.
Oncologic Efficacy: Clinically proven effective against a range of cancers, including ovarian, breast, non-small cell lung, colorectal, and other solid tumors.
Cell Cycle Disruption: Triggers cell cycle arrest precisely during mitosis, thereby suppressing malignant cell proliferation and tumor growth.
Clinical Evidence: Widely utilized in advanced cancer treatment regimens, with robust efficacy data supported by Phase II and Phase III clinical trials.
Product Overview
Paclitaxel is a diterpenoid compound originally extracted from the bark of Taxus brevifolia (Pacific yew). As a representative member of the taxane antineoplastic agents, it has become one of the most clinically valuable and widely applied chemotherapeutic drugs in contemporary oncology.
It has a molecular formula of C₄₇H₅₁NO₁₄, CAS registry number 33069-62-4, and a molecular weight of 853.9 g/mol. Paclitaxel appears as a white to off-white crystalline powder with high lipophilicity and low water solubility.
As a core component of mainstream chemotherapy regimens, paclitaxel is widely used in the treatment of various solid tumors and has been included in the WHO Model List of Essential Medicines.
2. Key Features
Distinctive Microtubule-Stabilizing Action: In contrast to traditional antimitotic drugs that suppress microtubule formation, paclitaxel actively promotes microtubule polymerization and enhances structural stability, thereby blocking the dynamic balance required for mitosis.
Wide-Ranging Antitumor Spectrum: It exhibits significant inhibitory effects against ovarian cancer, breast cancer, lung cancer, and AIDS-related Kaposi’s sarcoma, and also shows therapeutic potential against many other malignant tumors.
Cell Cycle Intervention at Multiple Stages: The agent mainly arrests cell proliferation in the late G2 and M phases; meanwhile, it can also interfere with interphase cells by destroying the connection between the nucleus and cytoskeleton.
Induction of Diverse Cell Death Pathways: Paclitaxel can activate several programmed cell death mechanisms including apoptosis, pyroptosis, ferroptosis, and necroptosis, which collectively enhance its antitumor effect.
Proven Clinical Value: Supported by long-term clinical application and extensive research, its dosage regimen, safety profile, and combined therapeutic strategies have been fully established and standardized.
Diversified Dosage Forms: In addition to the classic Cremophor EL-based preparation, advanced formulations such as albumin-bound paclitaxel (Abraxane®) have been developed to reduce solvent-associated adverse reactions.
Extended Applications in Interventional Devices: Outside the field of cancer therapy, paclitaxel-eluting balloons and stents are widely used in the treatment of peripheral arterial disease (PAD) to inhibit vascular restenosis.
3. Technical Specifications with Explanations
| Parameter | Typical Value/Specification | Description & Significance |
|---|---|---|
| CAS Number | 33069-62-4 | Universal chemical identifier |
| Molecular Formula | C₄₇H₅₁NO₁₄ | Complex diterpenoid structure with a taxane ring system |
| Molecular Weight | 853.9 g/mol | Used for stoichiometric calculations and formulation |
| Appearance | White to off-white crystalline powder | Visual quality indicator |
| Melting Point | 213-216°C (decomposes) | Characteristic physical constant |
| Solubility | Water: Practically insoluble Ethanol: Soluble Organic solvents: Soluble in DMSO, methanol, acetonitrile | High lipophilicity necessitates solubilizing agents (Cremophor EL) or advanced formulations |
| Partition Coefficient (log P) | 3.0 | High lipophilicity influences distribution and protein binding |
| Protein Binding | 89% | Extensively bound to plasma proteins |
| Metabolism | Hepatic via CYP2C8 and CYP3A4 | Major pathway for elimination; drug-drug interaction potential |
| Half-Life | 9.9 hours (3-hour infusion) | Nonlinear pharmacokinetics; dose and schedule dependent |
| Elimination | 71% feces (120 hours, 5% unchanged) 1.3-12.7% urine as unchanged drug | Primarily biliary excretion |
| Cross Blood-Brain Barrier | No | Limited CNS penetration |
4. Applications
Oncology Indications
Core Licensed Therapeutic Indications
Ovarian Cancer: Serves as a first-line option combined with cisplatin for advanced ovarian carcinoma, and is also applied as second-line intervention for metastatic lesions.
Breast Cancer: Applied as adjuvant therapy for lymph node-positive breast cancer following doxorubicin-based regimens; additionally used for metastatic cases unresponsive to combined chemotherapy or those relapsing within six months after adjuvant treatment.
Non-Small Cell Lung Cancer (NSCLC): Administered in combination with cisplatin as first-line therapy for patients unsuitable for radical surgical resection or radiotherapy.
AIDS-Related Kaposi’s Sarcoma: Recommended as a second-line therapeutic choice.
Off-Label and Guideline-Supported Applications
Interventional Cardiology and Vascular Surgery
Paclitaxel-eluting stents enable continuous and stable drug release, which helps sustain long-term arterial patency after stent implantation procedures.
5. Formulation & Product Comparison
| Parameter | Conventional Paclitaxel | Albumin-Bound Paclitaxel (Abraxane®) |
|---|---|---|
| Formulation | Cremophor EL (polyoxyethylated castor oil) + ethanol | Albumin-bound nanoparticles |
| Concentration | 6 mg/mL | Lyophilized powder for reconstitution |
| Administration | IV infusion over 1-24 hours with in-line filter | IV infusion over 30 minutes, no filter required |
| Premedication | Required: Dexamethasone + antihistamines + H2 antagonists to prevent hypersensitivity | Not required for hypersensitivity prevention |
| Dosing | 135-175 mg/m² every 3 weeks; weekly regimens available | 260 mg/m² every 3 weeks (breast); 100 mg/m² weekly (NSCLC, pancreatic) |
| Key Advantage | Decades of clinical experience, well-characterized | Eliminates Cremophol-related toxicities, higher tolerated dose, no premedication |
| Primary Indications | Ovarian, breast, NSCLC, Kaposi's sarcoma | Breast, NSCLC, pancreatic adenocarcinoma |
6. Dosing & Administration Guide
Standard Dosing Regimens
| Indication | Regimen | Dosing Schedule |
|---|---|---|
| Ovarian Cancer | 135-175 mg/m² IV | Every 3 weeks (with cisplatin) |
| Breast Cancer | 175 mg/m² IV | Every 3 weeks |
| NSCLC | 135 mg/m² IV | Every 3 weeks (with cisplatin) |
| Kaposi's Sarcoma | 135 mg/m² IV | Every 3 weeks; or 100 mg/m² every 2 weeks |
| Weekly Regimen | 80-100 mg/m² IV | Weekly (various solid tumors) |
Premedication Requirements
Standard 3-Week Regimen Premeds:
Dexamethasone 20 mg PO 12 and 6 hours prior OR 20 mg IV 30 minutes prior
Diphenhydramine 25-50 mg IV/PO 30-60 minutes prior
Ranitidine 50 mg IV or Famotidine 20 mg IV 30-60 minutes prior
Weekly Regimen Premeds (30-60 minutes prior):
Dexamethasone 10 mg IV
Diphenhydramine 25-50 mg IV/PO
Ranitidine 50 mg IV or Famotidine 20 mg IV
Dosage Adjustments for Toxicity
| Toxicity | Recommended Action |
|---|---|
| Febrile neutropenia | Reduce dose by 20% |
| Grade 4 neutropenia (≥5-7 days) | Reduce dose by 20% |
| Grade 4 thrombocytopenia | Reduce dose by 20% |
| Grade 3 neurotoxicity | Reduce dose by 20% |
| Grade 4 neurotoxicity | Discontinue |
| Cystoid macular edema (any grade) | Discontinue |
Administration Requirements
Dilution: Must be diluted prior to IV infusion
Filtration: Administer through in-line filter ≤0.22 μm
Sequence: When combined with platinum compounds, administer paclitaxel first
Infusion Solution Stability: 27 hours at room temperature (25°C) under ambient lighting
Storage: Store vials in original packaging at 15-30°C, protected from light
7. Safety & Tolerability Profile
Contraindications
Severe hypersensitivity to paclitaxel or polyoxyethylated castor oil (Cremophor EL)
Baseline neutrophil count < 1,500 cells/mm³ (solid tumors)
Baseline neutrophil count < 1,000 cells/mm³ (AIDS-related Kaposi's sarcoma)
Pregnancy (Category D)
Most Common Adverse Effects
| Adverse Effect | Incidence | Characteristics |
|---|---|---|
| Alopecia | 93% | Rarely permanent |
| Peripheral Neuropathy | 64% (severe 4%) | Dose-related and cumulative; presents as numbness, tingling, burning pain in glove-and-stocking distribution; usually improves/disappears months after treatment |
| Musculoskeletal Pain | 54% (severe 12%) | Appears 2-3 days after administration, resolves within days; NSAIDs effective |
| Nausea/Vomiting | 44% | Low emetogenic potential |
| Hypersensitivity | 40% (severe 1%) | Occurs in early courses, within first hour of infusion; prevented by premedication |
| Diarrhea | 25% | May be severe |
| Edema | 21% | |
| Fatigue | 17% | |
| Myelosuppression | Grade 4 neutropenia 27% | Dose and schedule-dependent; non-cumulative |
Serious Adverse Events [citation]
| Event | Notes |
|---|---|
| Anaphylaxis | 2% of patients; may be fatal |
| Cardiovascular | Hypotension (11%), arrhythmia (3%), bradycardia (usually asymptomatic) |
| Peripheral Neuropathy | Can be dose-limiting; mild symptoms usually reversible |
| Cystoid Macular Edema | Rare; reversible upon discontinuation |
| Interstitial Pneumonitis | Rare |
| Radiation Recall | Enhanced radiation injury to tissues; may occur weeks to months after radiation |
Special Populations
HIV Patients: Toxicity may be more severe, especially febrile neutropenia and infections
Prior Anthracycline Exposure: Congestive heart failure risk (including LVEF decrease) reported
8. Regulatory Status & Approvals
Global Regulatory Approvals
| Region/Country | Approved Indications | Identifier |
|---|---|---|
| United States (FDA) | Ovarian, breast, NSCLC, Kaposi's sarcoma | NDA 020262 |
| European Union (EMA) | Ovarian, breast, NSCLC, Kaposi's sarcoma | EMEA/H/C/000259 |
| Saudi Arabia (SFDA) | Ovarian, breast, NSCLC, Kaposi's sarcoma | Paclitaxel Kabi, 6 mg/mL |
| Taiwan | Ovarian, breast, NSCLC, Kaposi's sarcoma | BB21157221 (Taxol®) |
| Japan (PMDA) | Multiple solid tumors |
Key Regulatory Notes
Medical Device Applications：
Paclitaxel-coated balloons and stents used in the management of peripheral arterial disease (PAD) are classified and regulated as medical devices. The US Food and Drug Administration (FDA) has conducted comprehensive evaluations of related safety data and concluded that existing evidence does not indicate an increased risk of mortality associated with these devices.
Post-Marketing Safety Surveillance：
In 2019, an FDA-conducted meta-analysis initially raised a potential signal of delayed mortality linked to paclitaxel-coated devices. However, subsequent long-term follow-up studies—including the SWEDEPAD trial, VOYAGER PAD trial, and updated meta-analyses of randomized controlled trials (RCTs)—have failed to verify this risk. The FDA continues to advise standard clinical monitoring for patients and comprehensive communication regarding the benefits and risks prior to treatment.
9. Drug Interactions
Major Metabolic Interactions
| Drug Class/Agent | Effect | Clinical Implication |
|---|---|---|
| CYP2C8 Inhibitors (gemfibrozil, etc.) | May increase paclitaxel exposure | Monitor for increased toxicity |
| CYP3A4 Inhibitors (ketoconazole, erythromycin, etc.) | May increase paclitaxel exposure | Monitor for increased toxicity |
| CYP2C8/3A4 Inducers (rifampin, carbamazepine, etc.) | May decrease paclitaxel exposure | Potential for reduced efficacy |
Sequence-Dependent Interactions
Cisplatin/Carboplatin: Administer paclitaxel first to minimize myelosuppression
Doxorubicin: Administer paclitaxel after doxorubicin to avoid reduced doxorubicin clearance
10. Delivery, Certification & Service
Supply Chain Information
API Sources: Multiple qualified manufacturers worldwide
Finished Product: Available as 30 mg/5 mL, 100 mg/16.7 mL, 300 mg/50 mL vials (conventional); lyophilized powder for albumin-bound formulation
Storage Requirements: 15-30°C, protect from light
Shelf Life: Typically 24-36 months under proper storage
Quality Certifications
Certificate of Analysis (COA) provided with each batch
Safety Data Sheet (SDS) available in multiple languages
Product Specification (PS) documenting purity, identity, and strength
Certificate of Origin (COO) available upon request
Regulatory Documentation Available
Drug Master File (DMF) access for pharmaceutical manufacturers
GMP compliance documentation
REACH/TSCA compliance statements
Export documentation for international shipping
