asta-z-7557 and Lung-Neoplasms

Autologous bone marrow transplantation is used in small cell lung cancer (SCLC) to reverse the hematological toxicity induced by high dose therapy even though the presence of cancerous cells in the graft is potentially dangerous by reinfusion of the disease along with the hematopoietic stem cells. The present studies were undertaken to examine the effectiveness of anti-SCLC rat monoclonal antibodies LCA1 and LC66 plus human complement combined with a derivative of cyclophosphamide (Asta-Z 7557) for the elimination of cancerous clonogenic cells from the graft. In a series of assays conducted with three SCLC cell lines, used alone or mixed with normal bone marrow cells, the addition of Asta-Z 7557 to two cycles of treatment with monoclonal antibodies plus complement results in a 4- to 5-logarithmic reduction of the clonogenic SCLC cells detectable by limiting dilution analysis. This was superior to either treatment used alone. When normal bone marrow was submitted to the same treatment, a median (range) of 44% (15-77%) of the colony-forming unit, granulocyte-macrophage was recovered. These results suggest that the association of immunological (LCA1 and LC66 plus human complement) and pharmacological (Asta-Z 7557) removal methods is effective for purging metastatic clonogenic cells from bone marrow of SCLC patients and could be considered before autologous bone marrow transplantation.

Topics: Animals; Antibodies, Monoclonal; Bone Marrow; Bone Marrow Transplantation; Carcinoma, Small Cell; Cell Line; Cell Separation; Cell Survival; Cells, Cultured; Colony-Forming Units Assay; Complement System Proteins; Cyclophosphamide; Cytotoxicity, Immunologic; Hematopoietic Stem Cells; Humans; Lung Neoplasms; Rats; Transplantation, Autologous; Tumor Stem Cell Assay

ASTA Z 7557 is a stabilized cytostatic metabolite of cyclophosphamide which forms crystals at room temperature and releases 4-OH-cyclophosphamide in aqueous solution. The LD50/30 in mice after push injection is 417 mg/kg, after fractionated administration (q 6 hours X 4) 794 mg/kg. Daily treatment times 5 gives a LD50/30 value of 200 mg/kg. Depression of nucleated bone marrow cells and of leukocytes in the peripheral blood is observed after treatment. Recovery is slow. This holds true for push and fractionated administration. ASTA Z 7557 is a powerful cytostatic drug for treatment of an Ehrlich ascites tumor, a Lewis lung and a mammary carcinoma. Of two human tumor xenografts a malignant amelanotic melanoma responded with slight growth delay, whereas a gastric cancer did not.

Topics: Animals; Carcinoma, Ehrlich Tumor; Cell Division; Cyclophosphamide; Drug Evaluation, Preclinical; Humans; Lethal Dose 50; Lung Neoplasms; Male; Mammary Neoplasms, Experimental; Melanoma; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Neoplasm Transplantation; Neoplasms, Experimental; Stomach Neoplasms; Transplantation, Heterologous