Survival of mice bearing a transplanted syngeneic lymphoma following treatment with cyclophosphamide, 5-fluorouracil, or 1,3-bis(2-chloroethyl)-1-nitrosourea.
SUMMARY-A model has been derived for the effect of the chemotherapeutic agents cyclophosphamide (CY), 5-fluorouracil (5-FU), and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) on the survival of mice bearing a transplantable lymphoma. The model is based on assumptions that 1) failures in treatment result from the survival of viable malignant cells, 2) the lymphoma cells in the host increase exponentially with time, 3) the host dies when the lymphoma cell population reaches a critical value, and 4) the number of lymphoma cells in the host decreases exponentially as a function of the infected drug dose. Parameters were found for the growth of lymphoma cells in vivo and for the survival of lymphoma cells in the host following the administration of CY, 5-FU, and BCNU. When these parameters were incorporated into the model, predictions were obtained concerning the survival time of lymphoma-bearing mice as well as the fraction of long-term survivors as a function of the injected dose. It was found that the model and experimental data were in excellent agreement for low doses of the drug, i.e., doses which reduced the survival of the lymphoma cell population to the order of 10(-4) survival. However, discrepancies were observed above these dose levels. The discrepancies are discussed in terms of the assumptions of the model.
Bruce
W R
WR
Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
Valeriote
F A
FA
Meeker
B E
BE
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002330:Carmustine / Q000008:administration & dosage; D003520:Cyclophosphamide / Q000008:administration & dosage; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D008223:Lymphoma / Q000188:drug therapy*; D051379:Mice; D008806:Mice, Inbred AKR; D015233:Models, Statistical; D009368:Neoplasm Transplantation; D016019:Survival Analysis; D014185:Transplantation, Isogeneic; D017211:Treatment Failure; D016896:Treatment Outcome
D003520:Cyclophosphamide; D005472:Fluorouracil; D002330:Carmustine