High-dose thiotepa alone and in combination regimens with bone marrow support.

Area of Science:

• Oncology
• Hematology
• Pharmacology

Background:

• Curative cancer chemotherapy relies on dose-cytotoxicity relationships and combination therapy to prevent drug resistance.
• Dose escalation is often limited by myelosuppression, necessitating strategies like hematopoietic stem cell support.
• Hematopoietic stem cell transplantation has significantly improved outcomes for leukemia and lymphoma patients.

Purpose of the Study:

• To develop and evaluate a novel combination chemotherapy regimen for solid tumors, exploiting principles of curative cancer chemotherapy.
• To assess the efficacy and toxicity of a regimen comprising cyclophosphamide, thiotepa, and carboplatin in patients with measurable breast cancer.

Main Methods:

• A combination regimen of cyclophosphamide (6 g/m2), thiotepa (500 mg/m2), and carboplatin (800 mg/m2) was constructed and evaluated.
• The regimen's response rate and toxicity profile were assessed in women with measurable breast cancer.
• A phase II trial is evaluating this regimen in previously untreated metastatic breast cancer patients responsive to conventional chemotherapy.

Main Results:

• The novel regimen demonstrated an 81% response rate in women with measurable breast cancer.
• Profound myelosuppression was observed, but organ toxicity was rare.
• In a phase II trial, only one of 29 patients died of toxicity, confirming low treatment-related toxicity.

Conclusions:

• The developed regimen, utilizing cyclophosphamide, thiotepa, and carboplatin, exhibits high cytoreductive efficacy with low morbidity.
• This regimen represents a promising approach for curative cancer chemotherapy, particularly for solid tumors like breast cancer.
• Further evaluation in phase II trials confirms the regimen's safety and potential for treating metastatic breast cancer.