Solid tumour models for the assessment of different treatment modalities: IV. the combined effects of radiation and 5-fluorouracil

Abstract

Summary.-Neither radiation alone (375 to 1500 rad) nor 5 -fluorouracil (FU) alone (50-250 mg/kg) is sufficient to prevent an increase in the volume of the solid tumour model hepatoma 3924A. However, as little as 750 rad with 100 mg/kg FU can reduce the tumour below the volume at the time of treatment for as long as 14 days. A series of combined FU and radiation doses given every 11 days should then result in successively smaller tumour volumes until the tumour is eradicated.Changes in tumour volume were analysed by two different methods: (1) tumours in each treatment mode were grouped together and the average response to treatment determined, and (2) tumour volume changes in individual tumours were analyzed utilizing the x2 technique, which fits the logarithmic tumour volume change with time to polynomials. This two-directional method of analysis has the advantage of permitting both an overview of the main effects of treatment via the averages, and at the same time a detailed examination of the mechanism by which these effects occur through the analysis of individual responses. The results suggest that, in addition to concentrating on the cellular response immediately after therapy, greater emphasis should be placed on the kinetic changes of the tumour 1-3 weeks after single or multiple modality therapy. These findings demonstrate how the sequencing of single and/or combined treatment modalities may be investigated in order to determine how best to obtain maximum effects of treatment on different types of tumours following recovery of the host from the previous treatment series.

Solid Tumour Models for the Assessment of Different Treatment Modalities: vii: Single vs Fractionated Doses of 5-Fluorouracil on Two Solid Tumours and Their Hosts

“…Fractionation over the 3-or 5-day period prevents marrow recovery within the time necessary for animal survival. This delay in recovery increased the mortality rates from 10% in the large single-dose FU group to 60% for the 3 daily fractionated groups and 80% for the 5 The in vitro studies by Wolberg and Ansfield (1971) (Looney, et al, 1976b, c). In these experiments, the marrow recovery time after a single 50 mg/kg dose of FU is 7-8 days.…”

Solid tumor models for assessment of different treatment modalities: therapeutic strategy for sequential chemotherapy with radiotherapy.

“…Previous reports from these studies (1)(2)(3)(4)(5)(6) have demonstrated that recovery from the effects of a large dose of 5-fluorouracil (5-FUra) in rats occurs 10-11 days after treatment. The maximal rate of tumor volume change occurs 12 days after 5-FUra (4).…”

“…Studies on the solid tumor model hepatoma 3924A indicated that neither radiation alone [375-1500 roentgens (0.10-0.38 C/kg)] nor 5-FUra alone (50-250 mg/kg) would control tumor growth. However, these results suggested that radiation in combination with 5-FUra treatment could in principle transform the management of a chemotherapeutically resistant solid tumor from an untreatable situation to a treatable situation by the combined modality treatment every 11 days until the tumor is eradicated (2).…”