cyclophosphamide + mitoxantrone + thiotepa

The combination of cyclophosphamide, mitoxantrone, and thiotepa (often abbreviated as CTM) is a high-dose chemotherapy regimen primarily used in the treatment of breast cancer. This regimen was designed to minimize pulmonary injury that was commonly seen in carmustine-based regimens. ## Dosing and Administration The CTM regimen is typically administered over 4 days with the following dosages: - Cyclophosphamide: 6,000 mg/m² - Thiotepa: 600 mg/m² - Mitoxantrone: 24-60 mg/m² This high-dose chemotherapy is followed by autologous hematopoietic stem cell rescue to help patients recover from the intensive treatment. ## Clinical Outcomes In a study involving 191 breast cancer patients (99 stage II/IIIA, 27 stage IIIB, and 65 stage IV responsive to conventional-dose chemotherapy), the CTM regimen showed promising results: - For stage II/IIIA patients with 10 or more involved axillary lymph nodes, the 5-year event-free survival was 62±12% - For stage IIIB patients, the 5-year event-free survival was 44±19% - For stage IV patients, the 5-year event-free survival was 17±10% Notably, hormone receptor-positive patients with 10 or more nodes showed significantly better outcomes than hormone receptor-negative patients. Similarly, stage IV patients who achieved complete response in viscera and/or soft tissue prior to CTM did significantly better than those achieving only partial response. ## Safety Profile The treatment-related mortality was relatively low at 3% (6 deaths), including two due to diffuse alveolar hemorrhage. No episodes of delayed interstitial pneumonitis were reported. There were six severe cardiac events in 91 patients (6.6%), but none after instituting mitoxantrone dose-adjustment in the final 100 patients. The CTM regimen appears to be associated with low treatment-related mortality and minimal pulmonary toxicity, making it a viable option for certain breast cancer patients, particularly those with stage II/IIIA disease with 10 or more involved axillary lymph nodes.