What is the typical dosing regimen and management strategy for weekly paclitaxel in an adult patient with a good performance status and no significant comorbidities?

Weekly Paclitaxel Dosing and Management

For adult patients with good performance status and no significant comorbidities, weekly paclitaxel is typically administered at 80 mg/m² IV over 1 hour on days 1,8, and 15 of a 28-day cycle, or at 80-90 mg/m² IV weekly continuously. 1

Standard Weekly Dosing Regimens

Breast Cancer

• Paclitaxel 80 mg/m² IV weekly as a single agent 1
• Alternative: Paclitaxel 80-90 mg/m² IV weekly when combined with trastuzumab for HER2-positive disease 1
• When combined with bevacizumab: Paclitaxel 90 mg/m² IV on days 1,8, and 15 of a 28-day cycle 1
• The NCCN 2024 guidelines now designate dose-dense AC followed by weekly paclitaxel as a preferred regimen for adjuvant breast cancer treatment 1

Ovarian Cancer

• Paclitaxel 80 mg/m² IV on days 1,8, and 15 with carboplatin AUC 5-6 on day 1, every 3 weeks for 6 cycles (dose-dense regimen) 2
• Alternative weekly regimen: Paclitaxel 60 mg/m² IV followed by carboplatin AUC 2, both given weekly for 18 weeks 2
• The GOG 262 trial demonstrated that weekly paclitaxel with carboplatin showed similar progression-free survival to every-3-week dosing, with significantly longer median PFS (14.2 vs 10.3 months) in patients not receiving bevacizumab 1

AIDS-Related Kaposi Sarcoma

• Paclitaxel 100 mg/m² IV over 3 hours every 2 weeks (dose intensity 45-50 mg/m²/week) 3
• This schedule is less toxic than 135 mg/m² every 3 weeks and is preferred for patients with low performance status 3

Administration Guidelines

Infusion Duration and Preparation

• Weekly paclitaxel is administered as a 1-hour infusion, which minimizes myelosuppression compared to longer infusion times 1, 4
• All patients require premedication: dexamethasone 20 mg PO at 12 and 6 hours before infusion, diphenhydramine 50 mg IV 30-60 minutes prior, and either cimetidine 300 mg or ranitidine 50 mg IV 30-60 minutes before paclitaxel 3
• For AIDS patients, reduce dexamethasone to 10 mg PO instead of 20 mg 3

Critical Safety Monitoring

• Do not administer if neutrophil count is <1,500 cells/mm³ or platelet count is <100,000 cells/mm³ for solid tumors 3
• For AIDS-related Kaposi sarcoma, neutrophil count must be ≥1,000 cells/mm³ before initiating or repeating treatment 5, 3
• Reduce dose by 20% for subsequent courses if severe neutropenia (<500 cells/mm³ for ≥1 week) or severe peripheral neuropathy occurs 3

Toxicity Profile and Management

Expected Toxicities with Weekly Dosing

Weekly paclitaxel demonstrates a more favorable toxicity profile compared to every-3-week administration, with reduced hematologic toxicity but increased risk of anemia 1, 6

Key toxicities include:

• Increased anemia compared to 3-weekly schedules 1
• Sensory peripheral neuropathy (dose-related) 1, 3
• Grade 3 sensory neuropathy occurs more frequently with weekly dosing than with 3-weekly paclitaxel 1
• Reduced grade 4 neutropenia compared to 3-weekly schedules 1
• Myalgia/arthralgia affecting 60% of patients with severe symptoms in 6% 3

Common Pitfalls to Avoid

• Do not use plasticized PVC equipment for preparation or administration, as it leaches DEHP; use polyethylene-lined administration sets instead 3
• Monitor for hypersensitivity reactions despite premedication, though these occur in only 1-4% of patients with weekly dosing 1
• Neurotoxicity is cumulative and dose-related; consider dose reduction if grade 2 or higher neuropathy develops 3

Efficacy Considerations

Response Rates

• Single-agent weekly paclitaxel achieves response rates of 20-65% in advanced ovarian cancer 7, 8
• In metastatic breast cancer, response rates up to 86% have been achieved with weekly single-agent therapy 6
• Weekly paclitaxel can produce responses in tumors resistant to 3-weekly paclitaxel 8

Rationale for Weekly Dosing

The dose-dense weekly approach allows more sustained exposure of dividing tumor cells to cytotoxic concentrations, potentially allowing a larger percentage of cancer cells to enter the vulnerable phase of their cell cycle when paclitaxel is present 7, 6

Hepatic Impairment Adjustments

For patients with hepatic impairment receiving 3-hour infusions 3:

• Transaminases <10× ULN and bilirubin ≤1.25× ULN: 175 mg/m²
• Transaminases <10× ULN and bilirubin 1.26-2.0× ULN: 135 mg/m²
• Transaminases <10× ULN and bilirubin 2.01-5.0× ULN: 90 mg/m²
• Transaminases ≥10× ULN or bilirubin >5.0× ULN: Not recommended