Solid tumor models for the assessment of different treatment modalities:XVI. Sequential combined modality (cyclophosphamide–radiation) therapy

Abstract

A tumor cure rate of 60% was realized when three series of combined radiation (1500 rads) and cyclophosphamide (150 mg/kg) doses were given sequentially to rats with hepatoma 3924A and the time between modalities held constant at 7 days. This sequence was previously shown to enhance tumor sensitivity and diminish host toxicity. The first series was given on days 0 and 7; second, days 14 and 21; and third, days 28 and 35. The cure rate was reduced to 10% when the time of the second series was increased from 14 to 32 days (first series, days 0 and 7; second, days 32 and 39; and third, days 63 and 70). No cures were obtained when the time of the second series of combined cyclophosphamide and radiation was further increased from 14 to 40 days; however, this treatment schedule resulted in at least a threefold increase in life span over controls of 30 +/- 1 days. Two and three single 1500 rad doses of radiation given 14 to 40 days apart produced skin changes within accepted limits of normal tissue tolerance. No major long-term hematological changes in peripheral blood and bone marrow have been demonstrated to date following two and three courses of cyclophosphamide given 14 to 40 days apart. Experimental results indicate that the frequency and dosage of cyclophosphamide and radiation used are within clinically acceptable doses and scheduling.

Solid tumor models for the assessment of different treatment modalities: XXI. Comparison of different radiation dose schedules alone or in combination with cyclophosphamide

“…There are five different radiation dose fractionation schedules now under active investigation in clinical radiotherapy: ( 1 ) hyperfructionalion, in which conventional radiation doses per fraction (150-300 rad) are given two to three times daily; (2) suprrfiuctionution, in which small radiation doses per fraction (55-150 rad) are used two to four times daily; (3) hjpofractionation, in which higher doses per fraction are given fewer than five times per week; (4) split coiirsc jraclion, when the radiation is given followed by a period of rest (one to two weeks) between courses; and (5) inlraopuutive ra- diation, in which 2000-3000 rad are given as a single radiation dose directly to the tumor following surgical e x p o~u r e .~…”