Four-cycle high-dose therapy with hematopoietic support for metastatic breast cancer: No improvement in outcomes compared with single-course high-dose therapy

Multiple-cycle high-dose therapy with autologous hematopoietic progenitor c ell (AHPC) support has been used to deliver dose-intensive therapy. We have used this approach as well as single-cycle high-dose therapy in treating p atients with metastatic breast cancer. We present the outcomes of multiple- cycle high-dose therapies and compare them with those resulting from single -course high-dose therapies performed at a single institution. Fifty-five p atients received 4 cycles of intensive chemotherapy with AHPC support. Thre e multicycle regimens were sequentially applied. Twenty patients were enrol led to receive 4 cycles of high-dose mitoxantrone, thiotepa, and cyclophosp hamide. Nineteen subsequent patients received this regimen modified by the incorporation of paclitaxel. Sixteen patients received 2 cycles of high-dos e melphalan, thiotepa, and paclitaxel and 2 cycles of mitoxantrone, thiotep a, and paclitaxel. The results of all 3 multiple-cycle therapies are compar ed with those of 55 contemporaneous patients with metastatic breast cancer who received a single course of high-dose cyclophosphamide and thiotepa or cyclophosphamide, cisplatin, and BCNU (carmustine) with hematopoietic cell rescue. Multiple-cycle therapy was associated with more infectious complica tions, increased transfusion requirements, and increased hospital admission s. However, there were no significant differences in outcomes between the g roups. For 55 patients who received multiple-cycle therapy, the actuarial 3 -year overall survival rate was 36% (95% confidence interval [CI] 23%-49%); freedom from progression and event-free survival were both 15% (CI 5%-25%) . The median time to disease progression and median survival were 1.0 and 1 .6 years, respectively. For the 55 patients who underwent a single course o f high-dose therapy, the 3-year overall survival was also 36% (CI 18%-54%), whereas freedom from progression and event-free survival were both 19% (CI 7%-31%). The median time to progression and median survival were 0.8 and 2 .2 years, respectively. Within the constraints of this patient population, the outcomes of 4 cycles of high-dose therapy with AHPC support were not su perior to those resulting from single courses of high-dose therapy in the t reatment of patients with metastatic breast cancer.