What is Paclitaxel (chemotherapy medication) used for?

Paclitaxel: Comprehensive Overview

What Paclitaxel Is

Paclitaxel is a microtubule-stabilizing chemotherapy agent that arrests mitosis by stabilizing microtubules, leading to cellular apoptosis, and is FDA-approved for treating ovarian cancer, breast cancer, non-small cell lung cancer, and AIDS-related Kaposi's sarcoma. 1, 2

FDA-Approved Indications

Paclitaxel is indicated for:

• Ovarian cancer: As subsequent therapy for advanced carcinoma; as first-line therapy in combination with cisplatin 1
• Breast cancer: Adjuvant treatment of node-positive breast cancer (administered sequentially to standard doxorubicin-containing combination chemotherapy); treatment after failure of combination chemotherapy for metastatic disease or relapse within 6 months of adjuvant chemotherapy 1
• Non-small cell lung cancer (NSCLC): First-line treatment in combination with cisplatin for patients who are not candidates for potentially curative surgery and/or radiation therapy 1
• AIDS-related Kaposi's sarcoma: Second-line treatment 1

Mechanism of Action

Paclitaxel exerts its cytotoxic effect by arresting mitosis through microtubule stabilization, which prevents normal cell division and results in cellular apoptosis 3, 2. This mechanism makes it effective against rapidly dividing cancer cells 2.

Standard Dosing Regimens

Ovarian Cancer

Previously untreated patients (choose one of the following every 3 weeks) 1:

• Paclitaxel 175 mg/m² IV over 3 hours followed by cisplatin 75 mg/m² 1
• Paclitaxel 135 mg/m² IV over 24 hours followed by cisplatin 75 mg/m² 1

Previously treated patients 1:

• Paclitaxel 135 mg/m² or 175 mg/m² IV over 3 hours every 3 weeks 1

Breast Cancer

Adjuvant treatment 1:

• Paclitaxel 175 mg/m² IV over 3 hours every 3 weeks for 4 courses, administered sequentially to doxorubicin-containing combination chemotherapy 1

Metastatic disease 1:

• Paclitaxel 175 mg/m² IV over 3 hours every 3 weeks 1

Weekly regimens (commonly used in practice) 4:

• Paclitaxel 80 mg/m² IV weekly 4
• Paclitaxel 80-90 mg/m² IV weekly for 12 weeks 4

Non-Small Cell Lung Cancer

• Paclitaxel 135 mg/m² IV over 24 hours followed by cisplatin 75 mg/m² every 3 weeks 1

AIDS-Related Kaposi's Sarcoma

• Paclitaxel 135 mg/m² IV over 3 hours every 3 weeks, OR 1
• Paclitaxel 100 mg/m² IV over 3 hours every 2 weeks (dose intensity 45-50 mg/m²/week) 1

Common Combination Regimens

Breast Cancer Combinations

With bevacizumab (for metastatic disease) 4:

• Paclitaxel 90 mg/m² by 1-hour IV on days 1,8, and 15 4
• Bevacizumab 10 mg/kg IV on days 1 and 15 4
• Cycled every 28 days 4

With carboplatin 4:

• Paclitaxel 175 mg/m² IV on day 1 4
• Carboplatin AUC of 6 IV on day 1 4
• Cycled every 21 days 4

With trastuzumab (for HER2-positive disease) 4:

• Paclitaxel 80 mg/m² IV weekly for 12 weeks 4
• Trastuzumab 4 mg/kg IV with first dose of paclitaxel, followed by 2 mg/kg IV weekly to complete 1 year of treatment 4

Ovarian Cancer Combinations

Dose-dense weekly paclitaxel with carboplatin 4:

• Weekly paclitaxel with carboplatin has shown increased progression-free survival (28 vs 17 months; P = 0.0015) and 3-year overall survival (72% vs 65%; P = 0.03) compared with standard every-3-week therapy 4

Major Toxicities and Management

Dose-Limiting Toxicities

Myelosuppression 3, 4:

• Neutropenia is the primary dose-limiting toxicity 3
• Grade 3-4 neutropenia occurs in 19-28% of patients receiving paclitaxel monotherapy for metastatic breast cancer 4
• Do not administer if neutrophil count <1,500 cells/mm³ (solid tumors) or <1,000 cells/mm³ (AIDS-related Kaposi's sarcoma) 1
• Platelet count must be ≥100,000 cells/mm³ before treatment 1

Peripheral neuropathy 3, 4:

• Sensory peripheral neuropathy is common and dose-related 3
• Reduce dose by 20% for severe peripheral neuropathy in subsequent courses 1

Cardiovascular Toxicity

Bradycardia 4:

• Paclitaxel causes reversible sinus bradycardia with incidence ranging from 0.1% to 31% 4
• May induce bradycardia directly through actions on the Purkinje system or indirectly through its formulation vehicle, Cremophor EL 4
• When used in combination, paclitaxel enhances doxorubicin cardiotoxicity by altering doxorubicin pharmacokinetics and increasing myocyte formation of doxorubicinol 4

Hypersensitivity Reactions

Mandatory premedication 1, 4:

• Dexamethasone 20 mg PO approximately 12 and 6 hours before paclitaxel 1
• Diphenhydramine (or equivalent) 50 mg IV 30-60 minutes prior to paclitaxel 1
• Cimetidine 300 mg or ranitidine 50 mg IV 30-60 minutes before paclitaxel 1

For AIDS-related Kaposi's sarcoma patients, reduce dexamethasone to 10 mg PO (instead of 20 mg PO) due to immunosuppression 1

Other Common Toxicities

• Alopecia 5
• Malaise, myalgias, and arthralgias 5
• Asymptomatic bradycardia 5

Dose Modifications

For Severe Neutropenia

Reduce dose by 20% for subsequent courses if neutrophil count <500 cells/mm³ for a week or longer 1

For Hepatic Impairment

Patients with hepatic impairment are at increased risk of toxicity, particularly grade III-IV myelosuppression 1. Dosage adjustment for the first course should be based on transaminase and bilirubin levels, with further reductions based on individual tolerance 1.

Administration Considerations

Critical Administration Requirements

Avoid PVC equipment 1, 5:

• Contact of undiluted concentrate with plasticized PVC equipment is not recommended 1
• Paclitaxel leaches plasticizer (DEHP) from PVC infusion bags or sets 1, 5
• Store diluted solutions in glass, polypropylene bottles, or polypropylene/polyolefin plastic bags 1
• Administer through polyethylene-lined administration sets 1

Clinical Efficacy Data

Breast Cancer

Monotherapy response rates 6:

• Objective response rate in metastatic breast cancer (pretreated or chemotherapy-naive) is generally 20-35% 6
• Weekly paclitaxel has achieved response rates up to 86% as single-agent therapy 7

Combination therapy 6:

• Paclitaxel plus doxorubicin shows superior objective response rate and median duration of response compared to either agent alone 6
• Useful second-line option for anthracycline-resistant disease 6

Ovarian Cancer

First-line combination therapy 6:

• Paclitaxel plus cisplatin shows superior efficacy to cyclophosphamide/cisplatin in terms of progression-free survival and median duration of survival 6

Second-line therapy 6:

• Objective response rates for platinum-refractory metastatic ovarian cancer range from 15-48% 6

Non-Small Cell Lung Cancer

Paclitaxel in combination with cisplatin is effective first-line therapy for patients not candidates for curative surgery or radiation 1, 4.