Paclitaxel-HDFL

Paclitaxel-HDFL is a combination chemotherapy regimen consisting of paclitaxel and high-dose 5-fluorouracil plus leucovorin (HDFL). This combination therapy has been studied for treating various types of cancer, particularly advanced gastric cancer and metastatic breast cancer. The regimen typically involves weekly administration of paclitaxel via intravenous infusion (usually over 1-3 hours) followed by a 24-hour infusion of high-dose 5-fluorouracil plus leucovorin. The specific dosing schedule varies by cancer type and study protocol, but commonly includes administration on days 1, 8, and 15 of a 28-day cycle. ## Mechanism of Action Paclitaxel is a novel antimicrotubule agent that works by promoting the assembly of microtubules from tubulin dimers and stabilizing them by preventing depolymerization. This stability inhibits the normal dynamic reorganization of the microtubule network essential for vital cellular functions, ultimately leading to cell death. The 5-fluorouracil component of HDFL is a pyrimidine analog that interferes with DNA and RNA synthesis, while leucovorin (folinic acid) enhances the cytotoxic effects of 5-fluorouracil. ## Clinical Applications This combination regimen has shown efficacy in: - **Advanced Gastric Cancer**: A Phase II study demonstrated a 40.7% overall response rate in patients with advanced gastric cancer, with median time to progression of 6 months and overall survival of 10 months. - **Metastatic Breast Cancer**: In pretreated metastatic breast cancer patients, the regimen achieved a 60.7% response rate with median survival of 18.1 months and progression-free survival of 7 months. ## Dosing Regimens The typical dosing schedule includes: - Paclitaxel: 80-90 mg/m² as a 1-3 hour intravenous infusion - 5-Fluorouracil: 2,000-2,600 mg/m² as a 24-hour intravenous infusion - Leucovorin: 300 mg/m² intravenous infusion These are usually administered on days 1, 8, and 15 of a 28-day cycle. ## Side Effects Common toxicities associated with this regimen include: - Neutropenia (40%) - Diarrhea (33.3%) - Stomatitis (10%) - Neuropathy (53.3% grade 1-2, 6.7% grade 3-4) The combination appears to be generally well-tolerated, with manageable toxicity profiles in clinical studies.

Brand names

Taxol

Other names

Paclitaxel-HDFL regimenWeekly Paclitaxel plus HDFL