Relationship of tumor regrowth to tumor cell survival, tumor cure rates and host survival in a solid tumor model following combined chemotherapy and radiotherapy.
Endpoints available for comparison of two or more treatment arms in a clinical cancer trial include response rates (complete and partial), time to progression, and patient survival. In experimental systems, similar endpoints are available (tumor cell survival, tumor regrowth, tumor cure rates, and host survival), but there is opportunity for more precise measurements and a wider range for varying the independent variables. Radiotherapy alone was compared with an alternating schedule in which both radiotherapy and cyclophosphamide (CP) were given intermittently for a total of 3 courses of each. Radiotherapy was given as multiple, 250 cGy fractions per day (MFD) in 2-day courses. Cyclophosphamide alone (3 x 150 mg/kg) was equivalent in tumor effect to 3600 cGy of irradiation given with the MFD schedule. The experimental points for the combined modality treatments fell along the lower edge of the zone of additivity. Exprapolation of the plots of log surviving fraction vs. total radiation for the combined treatment predicted a 37% cure rate at 6000 cGy + CP. There was a high probability for long term control and tumor cures only with the highest total doses of radiation (6000, 7000 and 8000 cGy) when combined with CP. The results obtained in well defined experimental tumor models provide quantitative information of the interrelationship of the major determinants on end results of the effectiveness of treatment and acceptable host toxicity of combined chemotherapy and radiotherapy. The quantitative evaluation of these major determinants on treatment outcome in relationship to host toxicity is often difficult or impossible to obtain in clinical host toxicity is often difficult or impossible to obtain in clinical studies.(ABSTRACT TRUNCATED AT 250 WORDS)
Hopkins
H A
HA
Department of Biomedical Engineering, School of Medicine, University of Virginia Health Sciences Center, Charlottesville 22901.
Looney
W B
WB
Carter
W H
WH
Reto
D C
DC
Campbell
E D
ED
D000818:Animals; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D016016:Proportional Hazards Models; D011879:Radiotherapy Dosage; D051381:Rats; D011912:Rats, Inbred ACI; D013997:Time Factors
D003520:Cyclophosphamide