Cyclophosphamide, Paclitaxel, and Thiotepa (High-Dose Chemotherapy)

The combination of cyclophosphamide, paclitaxel, and thiotepa is a high-dose chemotherapy regimen used primarily in the treatment of advanced breast cancer. This combination has been studied in clinical trials, particularly for patients with metastatic breast cancer who have responded to conventional-dose therapy. ## Pharmacology and Mechanism of Action This regimen combines three different chemotherapeutic agents, each with distinct mechanisms: **Cyclophosphamide** is an alkylating agent that damages DNA by attaching to and damaging the DNA in cancer cells when they are in their resting phase. This DNA damage prevents cells from dividing, slowing or stopping cancer growth[1][4]. **Paclitaxel** (Taxol) is a taxane that works by damaging the structural "skeleton" that supports cancer cells. It interferes with the normal function of microtubules during cell division, preventing cancer cells from growing and dividing[7]. **Thiotepa** is an alkylating agent that also damages DNA, preventing cancer cell replication and growth[4][5]. ## Clinical Applications This combination has been studied in several clinical settings: - As high-dose chemotherapy with peripheral blood progenitor cell or stem cell support for metastatic breast cancer[1][4] - In sequential high-dose chemotherapy regimens for patients with advanced breast cancer[1][6] - As part of intensive chemotherapy protocols for patients who have failed conventional therapies[2][5] ## Administration The regimen has been administered in various ways: - In some protocols, cyclophosphamide (6,000 mg/m²), thiotepa (500 mg/m²), and carboplatin (800 mg/m²) were given by continuous infusion over 4 days[4] - Other studies used cyclophosphamide (2.5 g/m²) and thiotepa (225 mg/m²) administered intravenously with paclitaxel as a 120-hour continuous infusion[2] - Some protocols involve sequential administration of these agents in multiple cycles[1][6] ## Efficacy Clinical trials have shown promising results: - In one study, the combination produced response rates in excess of 50%, with complete responses continuing for a median of 16 months after transplant[4] - Another trial reported an overall response rate of 87% in patients with measurable disease[1] - The regimen has demonstrated effectiveness in chemosensitive patients, particularly those who have failed high-dose methotrexate-based treatment[5] ## Toxicity Common side effects and toxicities include: - Mucositis (stomatitis or non-infectious diarrhea) has been identified as a dose-limiting toxicity[2] - Reversible sensory polyneuropathy, particularly following paclitaxel infusion[1] - Hematologic toxicity requiring stem cell support[5][6] - Potential for CNS toxicity, particularly in patients who have previously received cranial irradiation[5] This high-dose chemotherapy combination represents an intensive approach for treating advanced breast cancer, particularly in patients who have responded to conventional therapy but require more aggressive treatment to achieve durable responses.

Other names

High-dose paclitaxel, cyclophosphamide, and thiotepa regimen