Reduction of metastatic carcinoma cells in bone marrow by intravenously administered monoclonal antibody: towards a novel surrogate test to monitor adjuvant therapies of solid tumours.
In a pilot, prospective randomised study, 40 patients with breast and colorectal cancer presenting with metastatic cytokeratin (CK)-positive tumour cells in bone marrow were treated either with six doses of 100 mg of a monoclonal Lewis Y antibody during 2 weeks or with a placebo regimen, consisting of six infusions of human serum albumin (HSA). CK-positive cells in marrow were monitored prior to and on days 15 and 60 after commencement of treatment. In 30 patients presenting with relatively low tumour cell numbers (1-11 per 4 x 10(5) bone marrow cells), a therapy-induced reduction of CK-positive cells could not be conclusively determined. More meaningful quantitative data were obtained in 10 breast cancer patients presenting with more than 20 tumour cells per 4 x 10(5) nucleated bone marrow cells. 7 of these patients had been randomised to the antibody arm, and 5 showed an eradication or a distinct reduction of CK-positive/Lewis Y-positive cells of at least one log unit, while 2 patients, presenting with Lewis Y-negative tumour cells, showed no corresponding decrease. Similarly, in all 3 patients randomised to the placebo arm, tumour cells were not reduced. Because the antibody exerted a marked cytotoxicity on tumour cell lines when tested ex vivo in serum taken from these patients after antibody infusion, we postulate that the observed, prompt reduction of individual tumour cells in bone marrow was due to the cytotoxic action of the injected antibody. Although monitoring micrometastatic cells in bone marrow of patients with high tumour cell counts appears to be feasible, the immunocytochemical assay needs to be improved for patients with lower cell numbers before it can be applied as a surrogate test for adjuvant therapies.
Medical Clinic II, Zentralkinikum, Augsburg, Germany.
G
G
Schlimok
K
K
Pantel
H
H
Loibner
I
I
Fackler-Schwalbe
G
G
Riethmüller
D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D019046:Bone Marrow Neoplasms / Q000556:secondary* / Q000628:therapy; D001943:Breast Neoplasms / Q000473:pathology*; D017024:Chemotherapy, Adjuvant; D015179:Colorectal Neoplasms / Q000473:pathology*; D005260:Female; D006801:Humans; D007983:Lewis Blood Group Antigens / Q000276:immunology; D018365:Neoplasm, Residual; D010865:Pilot Projects; D011446:Prospective Studies
D000911:Antibodies, Monoclonal; D007983:Lewis Blood Group Antigens