[Antitumor activity of BOF-A2, a new 5-fluorouracil derivative, against human cancers xenografted in nude mice by intermittent administration].
Antitumor effects of BOF-A2 given intermittently was evaluated with human gastric (H-111, H-83), colorectal (H-110, H-143) and lung (H-74, LC-376) cancers xenografted in nude mice and compared with those by continuous administration. BOF-A2 was orally given 3 or 4 times per week at 30 or 35 mg/kg over 4 weeks. This drug was effective to 5 strains except H-110 (IR > or = 58%), remarkably effective to H-81 and H-143 (IR > or = 80%) and caused tumor regression in mice bearing H-81 especially. Moreover, the drug was effective to H-74 which is rather insensitive to 5-FU and its known derivatives. When the drug was given orally to nude mice xenografted LC-376, 5-FU levels in the tumor tissue was notably durative for a long time as compared to UFT. It would be concluded that BOF-A2 was much effective to insensitive tumor to fluorinated pyrimidines or other anticancer, because of persistence of high levels of 5-FU in the tumor tissue. On the other hand, diarrhea which is caused by other fluorinated pyrimidines or consecutive administration of BOF-A2, was mild by the intermittent administration of BOF-A2.
Fujita
F
F
Dept. of Surgery, Osaka University, Suita, Japan.
Fujita
M
M
Inaba
H
H
Taguchi
T
T
D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols; D001835:Body Weight / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D005641:Tegafur / Q000008:administration & dosage; D014498:Uracil / Q000008:administration & dosage
D000970:Antineoplastic Agents; D005641:Tegafur; D014498:Uracil; C053194:Emitefur; D005472:Fluorouracil