[Effect of cyclophosphamide on neuroblastoma and the bone marrow function in the experimental studies]

The potential difference in survival and antitumor effect due to different dosage schedules of cyclophosphamide (CPM) treatment was analyzed in A/J mice inoculated with mouse neuroblastoma C 1300 Cells, which closely resembles the human neuroblastoma in its capacity of cathecolamin secretion and in response to chemotherapy. 10(6) neuroblastoma cells were inoculated subcutaneously on the back, and when the tumor grow to 1.0-1.5 cm in diameter, treatment with CPM was started. Until the observation of death, tumor size, peripheral neutrophil number and CFU-C (colony-forming unit in culture) in bone marrow and spleen were measured periodically. In the first experiment, the anti-tumor effect of CPM in one dose ranged from 100 mg to 400 mg/kg was studied. The anti-tumor effect was closely correlated with the dose of CPM given intraperitoneally, however the survival of mice inoculated with higher dose of CPM (300 mg or 400 mg/kg) were significantly shorter than that of control, suggesting that these groups resulted in chemotherapy death. To learn exact anti-tumor effect of the higher doses, bone marrow rescue was performed in these groups received 300 mg or 400 mg/kg of CPM, in the second experiment. Infusion of 5-10(6) syngeneic bone marrow cells 12 hours after the inoculation of CPM resulted in the prolongation of survival; mean survival of the group without bone marrow rescue was 5 days, and that with bone marrow rescue was 60 days. However this procedure was not a potentially curative treatment modality. In the third experiments the effect of intermittent inoculation of sublethal dose of CPM (200 mg/kg) was studied. Inoculation of the drug at the interval of 2 weeks resulted in the longest survival, and those at the shorter interval induced chemotherapy death. In the following experiment, 200 mg/kg of CPM was given in 4 divided doses for 4 consecutive days at the interval of 2 weeks, and the anti-tumor effect was compared with that observed in the group received one single dose. There observed no significant difference in survival time between 2 groups, however the latter procedure (one single dose) was more effective for the control of tumor growth. Furthermore, hematological analyses revealed that the recovery of granulopoiesis was significantly earlier in the group with one single dose than that with 4 divided dose, which was confirmed by granulocyte count and CFU-C analysis.(ABSTRACT TRUNCATED AT 400 WORDS)