Combination of high-dose chemotherapy and monoclonal antibody in breast-cancer patients: a pilot trial to monitor treatment effects on disseminated tumor cells

Background Tumor relapse occurring in high-risk breast cancer patients after high-dose chemotherapy (HDC) and autologous stem-cell transplantation may arise from cells resistant to chemotherapy, as well as fi-om tumor cells reinfused wi th autologous stem cell grafts. This pilot study was designed to investigat e whether ex vivo immunomagnetic purging of PBSC and subsequent immunothera py with MAb 17-1A is feasible and can reduce the number of disseminated tum or cells in BM. Methods Twelve high-risk breast-cancer-patients, seven in Stage II/III and five in Stage IV (UICC breast cancer classsification) underwent surgery of the prim ary tumor and received two cycles of induction chemotherapy, followed by HD C. After each cycle of induction chemotherapy PBSC were collected and incub ated with Ad-coated immunomagnetic beads, to remove contaminating tumor cel ls. Prepared stem-cell grafts were transplanted 24 h after completion of HD C. After recovering from HDC all 12 patients received a total dose of 900 m g MAb 17-IA within 4 months The effect of in vivo purging with MAb 17-1A af ter HDC was controlled by examining bone aspirates of the patients with an immunocytochemical assay, allowing the detection of one cytokeratin-positiv e tumor cell in Id total nucleated cells (TNC). Results Tumor cells were found in 5/12 BM aspirates prior to chemotherapy and even after HDC. Further monitoring of BM aspirates for cancer cells during Ab th erapy showed a consistent reduction of tumor cells in four oat of these fiv e patients After a median clinical follow-up of 41 (32-48) months all four patients ave alive These results are different from those of a historical c ontrol group of six patients with breast cancer treated with the same chemo therapy schedule but without 17/1A consolidation. In comparison with the pa tients from the study group all patients of this control group revealed a s ignificantly increased number of tumor cells in BM (p < 0.01) after HDC dur ing follow-up of 5 (3-7) months. These preliminary results indicate that in duction chemotherapy, followed by HDC, may reduce disseminated tumor cells in BM. Discussion Immunotherapy with MAb 17-1A after HDC may further eliminate residual disea se without severe toxicity.