SOLID TUMOR-MODELS FOR THE ASSESSMENT OF DIFFERENT TREATMENT MODALITIES .20. COMPARISON OF EFFECTS OF DAILY VERSUS HYPERFRACTIONATED SPLIT-COURSE RADIATION SCHEDULES WITH AND WITHOUT CYCLOPHOSPHAMIDE ON MEDIAN SURVIVAL, METASTATIC DISSEMINATION, TUMOR CURE, AND GROWTH-RATES

  • 1 January 1983
    • journal article
    • research article
    • Vol. 43  (1) , 60-67
Abstract
Daily fractions of 188, 250, 375, 500 and 750 rad were given to rats with [rat] hepatoma 3924A so that all groups received the same weekly dose of 1500 rad over a 6-wk period, for total doses of 9000 rad when only radiation was given and 4500 rad when combined with cyclophosphamide. No tumors were cured (with 2 exceptions) with or without 3 doses of cyclophosphamide (150 mg/kg or 0.9 g/m2) given 14 days apart. The addition of cyclophosphamide to the daily radiation treatment schedules did not change the time for tumors to reach 8 times the volume at time of treatment but did result in a longer median survival, which was attributed to a reduction of pulmonary metastases. A hyperfractionated radiation schedule using six 250-rad fractions given 3 times daily every 4 h for 2 days combined with cyclophosphamide (150 mg/kg) 1 day later and repeated 2 additional times at 11-day intervals for a total dose of 4500 rad and cyclophosphamide (450 mg/kg) resulted in eradication of 6 of 10 tumors, for a cure rate of 60%. Skin damage, determined by visually scoring the skin, appeared to be fully recovered by Day 126 and remained so until the end of the experiment on Day 384. The 3 courses of hyperfractionated radiation (total dose, 4600 rad), when given alone, were ineffective in producing tumor regression and cure. Combining cyclophosphamide with hyperfractionated split-course radiation schedules gave a major increase in tumor cure rate as compared with radiation alone at the same (4500 rad) or higher (9000 rad) doses. The major gains in effective utilization of the 2 modalities is greatly diminished or lost when the radiation is administered as daily fractions.