A short course of induction chemotherapy followed by two cycles of high-dose chemotherapy with stem cell rescue for chemotherapy naive metastatic breast cancer: sequential phase I/II studies

Two cycles of high-dose chemotherapy with stem cell support (HDC) may incre ase the total dose delivered and dose intensity. A brief induction phase an d different non-cross-resistant agents for each HDC cycle were used to avoi d drug resistance. Twenty-six women with metastatic BC had induction and st em cell mobilization with two cycles of doxorubicin/G-CSF given every 14 da ys. Patients with stable disease or better after induction received HD CTCb followed by HD melphalan and dose-escalated paclitaxel. At 475 mg/m(2) of paclitaxel by 24-h infusion, dose-limiting transient peripheral sensory neu ropathy was encountered. No toxic deaths occurred. Complete and near comple te response after completion of therapy was achieved in 22 (85%) of 26 pati ents. The median EFS was 38 months. The median OS has not yet been reached. At a median follow-up of 33 (25-43) months, actuarial EFS and OS were 54% (95% confidence interval (CI), 39-69%) and 69% (95% CI, 56-79%), respective ly. This double transplant approach lasts only 14 weeks and is feasible, sa fe, and tolerable. Whilst selection biases may in part contribute to favora ble EFS and OS, a randomized comparison of standard therapy vs double trans plant in both metastatic and locally advanced breast cancer is warranted.