[Evaluation of antitumor activity of etoposide administered orally for 21 consecutive days against human uterine cancer subcutaneous and/or orthotopic xenografts in nude mice].
The antitumor activity of etoposide (ETP) against human uterine cancer cell lines were investigated in vitro and in vivo. The cytotoxic activity of ETP against HeLa S3, a human cervical cancer cell line, depended on exposure time. The survival rate with 24 h prolonged exposure was reduced to about 1/200 that with 6 h exposure. The time dependency of antitumor activity of ETP against HeLa S3 subcutaneously transplanted in nude mice was studied. The effect of 21 or 28 consecutive days oral administration was greater than that of 5 or 14 consecutive days. Furthermore, a longer administration schedule was less toxic. The antitumor activity of ETP administered orally for 21 consecutive days was compared with that of CDDP, CPT-11 and 5'-DFUR using both human uterine cancer cell lines (TCO-1, SIHA, UCC08JCK) transplanted subcutaneously in nude mice and human uterine cancer cell lines (HeLa S3, UCC08JCK) transplanted into the uterus of nude mice. ETP showed the same antitumor activity as CPT-11 and 5'-DFUR against TCO-1 and UCC08JCK, human uterine cancer cell lines transplanted subcutaneously in nude mice. ETP also showed anticancer activity against two cell lines transplanted into the uterus. The growth inhibition caused by ETP administered orally at 50 mg/kg against HeLa S3 transplanted subcutaneously was 36.7% while that against the same cell line transplanted into the uterus was 58.5%. 5'-DFUR also showed the same antitumor activity as ETP. These results suggest that long term oral administration of ETP is clinically useful for cervical cancer patients.
Matsumoto
S
S
Anticancer Drugs Dept., Nippon Kayaku Co., Ltd.
Mashiba
H
H
Okamoto
K
K
Ekimoto
H
H
D000230:Adenocarcinoma / Q000188:drug therapy; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000627:therapeutic use; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000473:pathology; D002945:Cisplatin / Q000627:therapeutic use; D005047:Etoposide / Q000008:administration & dosage / Q000627:therapeutic use*; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use; D006801:Humans; D000077146:Irinotecan; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D012867:Skin / Q000473:pathology; D014183:Transplantation, Heterologous; D014594:Uterine Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D005467:Floxuridine; D005047:Etoposide; D000077146:Irinotecan; D002945:Cisplatin; C025034:doxifluridine; D002166:Camptothecin