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 from tumor cells reinfused with autologous stem cell grafts. This pilot study was designed to investigate whether ex vivo immunomagnetic purging of PBSC and subsequent immunotherapy with MAb 17-1A is feasible and can reduce the number of disseminated tumor cells in BM.


METHODS
Twelve high-risk breast-cancer patients, seven in Stage II/III and five in Stage IV (UICC breast cancer classification) underwent surgery of the primary tumor and received two cycles of induction chemotherapy, followed by HDC. After each cycle of induction chemotherapy PBSC were collected and incubated with Ab-coated immunomagnetic beads, to remove contaminating tumor cells. Prepared stem-cell grafts were transplanted 24 h after completion of HDC. After recovering from HDC all 12 patients received a total dose of 900 mg MAb 17-1A within 4 months. The effect of in vivo purging with MAb 17-1A after HDC was controlled by examining bone aspirates of the patients with an immunocytochemical assay, allowing the detection of one cytokeratin-positive tumor cell in 10(6) 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 therapy showed a consistent reduction of tumor cells in four out of these five patients. After a median clinical follow-up of 41 (32-48) months all four patients are alive. These results are different from those of a historical control group of six patients with breast cancer treated with the same chemotherapy schedule, but without 17/1A consolidation. In comparison with the patients from the study group, all patients of this control group revealed a significantly increased number of tumor cells in BM (p < 0.01) after HDC during follow-up of 5 (3-7) months. These preliminary results indicate that induction chemotherapy, followed by HDC, may reduce disseminated tumor cells in BM.


CONCLUSIONS
Immunotherapy with MAb 17-1A after HDC may further eliminate residual disease without severe toxicity.
Hempel
P
P
Medical Clinic II and Institute of Laboratory Medicine, Central Hospital Augsburg, Germany.
Müller
P
P
Oruzio
D
D
Behr
W
W
Brockmeyer
C
C
Wochner
M
M
Ehnle
S
S
Riethmüller
R
R
Schlimok
G
G
D000328:Adult; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology* / Q000532:radiotherapy; D002945:Cisplatin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D003402:Creatine Kinase / Q000378:metabolism; D015251:Epirubicin / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007069:Ifosfamide / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D007167:Immunotherapy; D008875:Middle Aged; D009367:Neoplasm Staging; D010865:Pilot Projects; D018714:Radiotherapy, Adjuvant; D015996:Survival Rate
D000911:Antibodies, Monoclonal; D015251:Epirubicin; D005047:Etoposide; D003402:Creatine Kinase; D002945:Cisplatin; D007069:Ifosfamide