For the purpose of examining the biochemical modulation function of Leucovorin (LV) on an antitumor effect 5-fluorouracil (5-FU), the following tests were carried out. In order to conduct in vitro (HTCA) and in vivo chemosensitivity tests taken two human tumor xenografts (MC-3, MPC-2).
Testing in vivo, the dose was set at LD
50x0.8 (single therapy) and LD
50x0.6 (combined therapy) for 5-FU. In the cases testing LV, the dose was set at 0.45mg/body.
Testing in vitro, the dosage was regulated at μg/ml for 5-FU and at 0.15mg/m l for LV. The antitumor effects of the drugs in vivo were evaluated according to the Battle Columbus Laboratories Protocol.
The results of the in vivo were no effects on MC-3. However, 5-FU was evaluated at 41.2% and 5-FU LV at 39.8% on MPC-2.
The results of the in vitro were no effects on MC-3. However, 5-FU was evaluated at 51.8% and 5-FU LV at 61.6% on MPC-2. The results of in vivo and in vitro show that in cases using MC-3 and MPC-2, LV did not enhance the antitumor effect of 5-FU.
We also investigated the relationship between the antitumor activity of the drugs and their inhibition of thymidylate synthase (T.S) activity in MC-3. There was no correlation between both relation.
We conclude that further investigations are necessary to determine the appropriate dose of 5-FU, so that an effective concentration of the drug can be attained at tumor tissue level. Moreover, we need to establish the appropriate time for given the infusion of LV to obtain an adequate enhancement of the antitumor effect of 5-FU.
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