What is the evidence for IV paclitaxel (paclitaxel) 100mg/M2 every 2 weeks dosing for Kaposi sarcoma, including guidelines from organizations such as the National Comprehensive Cancer Network (NCCN)?

Evidence for IV Paclitaxel 100mg/M² Every 2 Weeks for Kaposi Sarcoma

The FDA-approved and NCCN-recommended regimen for AIDS-related Kaposi sarcoma is paclitaxel 100 mg/m² IV over 3 hours every 2 weeks, with a target dose intensity of 45-50 mg/m²/week. 1

FDA-Approved Dosing Regimen

The FDA label explicitly states that for patients with AIDS-related Kaposi's sarcoma, paclitaxel administered at a dose of 100 mg/m² given intravenously over 3 hours every 2 weeks is recommended (dose intensity 45 to 50 mg/m²/week). 1 The FDA notes that in the 2 clinical trials evaluating different schedules, the alternative schedule of 135 mg/m² every 3 weeks was more toxic than the 100 mg/m² every 2 weeks regimen. 1

NCCN Guideline Recommendations

The NCCN guidelines (2019) recognize paclitaxel as a first-line systemic therapy option for both limited cutaneous and advanced AIDS-related Kaposi sarcoma. 2 The guidelines note that paclitaxel and pegylated-liposomal doxorubicin are statistically equivalent with regard to response rates, median progression-free survival, and 2-year survival. 2

Clinical Trial Evidence Supporting This Regimen

Efficacy Data

The 100 mg/m² every 2 weeks regimen has demonstrated robust efficacy across multiple studies:

• Response rate: 56-59% in patients with advanced AIDS-related Kaposi sarcoma, including those previously treated with systemic chemotherapy. 3, 4
• Median duration of response: 8.9-10.4 months, which is among the longest observed for any regimen reported for AIDS-related KS. 3, 4
• Median survival: 15.4 months in heavily pretreated populations. 3
• The regimen was effective even in patients who had failed prior anthracycline therapy (71% had received prior systemic therapy; 31 were anthracycline-resistant). 3

Head-to-Head Comparison

A randomized trial directly comparing paclitaxel 100 mg/m² every 2 weeks versus pegylated liposomal doxorubicin 20 mg/m² every 3 weeks showed:

• Comparable response rates (56% vs 46%; P=0.49) 5
• Comparable median progression-free survival (17.5 months vs 12.2 months; P=0.66) 5
• Comparable 2-year survival rates (79% vs 78%; P=0.75) 5
• A trend toward increased grade 3-5 toxicity with paclitaxel (84% vs 66%; P=0.077), including 1 fatal pulmonary embolism 5, 2

Safety Profile and Monitoring Requirements

Toxicity Profile

The main toxicities with the 100 mg/m² every 2 weeks regimen include:

• Grade 3-4 neutropenia: 35-61% of patients 3, 4
• Mild-to-moderate alopecia: 87% of patients 3
• Neutropenic fever is uncommon despite the high rate of neutropenia 4

Special Modifications for AIDS Patients

The FDA label mandates specific modifications for immunosuppressed AIDS patients: 1

1. Reduce premedication dexamethasone to 10 mg PO (instead of the standard 20 mg PO for other indications)
2. Initiate or repeat treatment only if neutrophil count ≥1,000 cells/mm³ (lower threshold than the 1,500 cells/mm³ required for solid tumors)
3. Reduce dose by 20% for subsequent courses if severe neutropenia occurs (neutrophil <500 cells/mm³ for ≥1 week)
4. Initiate concomitant G-CSF as clinically indicated

Standard Premedication Protocol

All patients require premedication to prevent severe hypersensitivity reactions: 1

• Dexamethasone 10 mg PO at 12 and 6 hours before paclitaxel (for AIDS patients)
• Diphenhydramine 50 mg IV 30-60 minutes prior
• Cimetidine 300 mg or ranitidine 50 mg IV 30-60 minutes prior

Quality of Life Benefits

Treatment with paclitaxel produces significant symptom palliation: 5

• Significant improvements in pain (P=0.024) and swelling (P<0.001)
• Of patients reporting pain interfering with activities at baseline, 69% improved
• Of patients with swelling at baseline, 93% improved

Clinical Context and Patient Selection

This regimen is particularly appropriate for:

• Patients with advanced AIDS-related Kaposi sarcoma (≥25 mucocutaneous lesions, visceral disease, or lymphedema) 4
• Patients who have failed or are refractory to prior systemic therapy, including liposomal anthracyclines 3, 4
• Patients with low performance status (all patients with Karnofsky performance status ≤70 in FDA trials received the 100 mg/m² every 2 weeks schedule rather than the more toxic 135 mg/m² every 3 weeks schedule) 1

Important Caveats

The 100 mg/m² every 2 weeks schedule was specifically chosen over the 135 mg/m² every 3 weeks schedule because it was less toxic, despite similar dose intensity. 1 The NCCN guidelines note that a systematic review found no evident differences between liposomal doxorubicin and paclitaxel in advanced AIDS-related Kaposi sarcoma, though the number of studies was limited. 2