Comparative antitumor activity of 5-fluorouracil and 5'-deoxy-5-fluorouridine in combination with radiation therapy in mice bearing colon 26 adenocarcinoma.
The present study compared the antitumor activities of chemotherapy with 5-fluorouracil (5-FU) and with its prodrug 5'-deoxy-5-fluorouridine (5'-DFUR) in combination with radiotherapy on a solid colon 26 adenocarcinoma in the mouse. A single administration of 5'-DFUR immediately after local irradiation on day 10 after tumor inoculation produced more than additive antitumor effects, while only an additive effect was observed in the combined treatment with 5-FU and radiation. This over-additive effect of 5'-DFUR was more obvious in a fractionated-dose treatment schedule, where the same combined modality treatment was given three times on days 6, 10 and 14 after inoculation of the tumor cells. 5'-DFUR enhanced the radiation effects on the tumor in terms of the delay in tumor growth as well as the increase in the survival time. 5-FU produced only a marginal additive antitumor effect. Furthermore, radiation damage to normal tissues (skin damage by local irradiation and bone marrow and spleen damage by whole-body irradiation) was not enhanced by 5'-DFUR, though radiation damage to the thymus was additive. On the other hand, 5-FU produced toxic effects that were additive for all normal tissues tested. Thus, at doses that were the most effective against tumors, relative therapeutic gain factors (the ratio of the effect on tumors to that on the bone marrow) of 5'-DFUR and 5-FU were 1.24 and 0.49, respectively. These results suggest that 5'-DFUR will have a greater potential than 5-FU in combined modality treatment of cancer patients.
Ishikawa
T
T
Nippon Roche Research Center, Kanagawa.
Tanaka
Y
Y
Ishitsuka
H
H
Ohkawa
T
T
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001853:Bone Marrow / Q000473:pathology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy; D003131:Combined Modality Therapy; D005260:Female; D005467:Floxuridine / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D005472:Fluorouracil / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D013154:Spleen / Q000473:pathology; D013950:Thymus Gland / Q000473:pathology; D015430:Weight Gain
D000970:Antineoplastic Agents; D005467:Floxuridine; D005472:Fluorouracil; C025034:doxifluridine