Combining independently effective anticancer agents may not augment the independent antitumor effects: A study using human digestive organ cancer xenograft lines in nude mice

Yoshinori Nio, Chen‐Chiu ‐C Tseng, Michihiko Tsubono, Kazuya Kawabata, Yoshikazu Masai, Takahiro Shiraishi, Manabu Fukumoto, Takayoshi Tobe

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Five human digestive organ cancer xenograft lines were subcutaneously transplanted in nude mice, and 7 anticancer agents (ACAs) were intravenously administered singly or in combinations at 4 times the standard clinical doses. Cisplatin (P) was effective in 4 lines and 5‐fluorouracil (F) was effective in 3 lines. A total of 8 combinations with 2 effective ACAs were assessed in 4 lines and only 1 combination (FP) resulted in an augmented antitumor effect in a single line. A total of 11 combinations with 1 effective ACA plus 1 ineffective ACA were assessed in 2 lines, and only 1 combination (F + carboquone [CQ; Esquinon]) resulted in an augmented effect in a single line. A total of 5 combinations with independently ineffective ACAs were assessed in 1 line, and 1 combination (FP) resulted in augmented antitumor activity. No 2‐ACA combinations showed enhanced side effects. Two combinations with 3 effective ACAs were assessed in 2 lines and 1 combination (FP + mitomycin C) resulted in an augmented effect with a greater mortality rate. A total of 12 combinations with both effective plus ineffective ACAs were assessed in 2 lines, and 3 combinations (FP + Adriamycin or FP + CQ or FP + etoposide) resulted in an augmented effect in 1 line with enhanced side effects. These results indicate that the combination of independently effective ACAs does not always cause an augmented antitumor effect, and may sometimes result in augmented side effects. According to this study, the 3‐ACA combinations with FP + 1 effective agent appear to be the best regimens for digestive organ cancer.

Original languageEnglish
Pages (from-to)252-259
Number of pages8
JournalJournal of Surgical Oncology
Volume48
Issue number4
DOIs
Publication statusPublished - 1991 Dec

Keywords

  • chemotherapy
  • digestive organ cancer
  • human tumor xenograft
  • nude mouse
  • synergism

ASJC Scopus subject areas

  • Surgery
  • Oncology

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