Pharmacokinetics and anti-tumour activity of LM985 in mice bearing transplantable adenocarcinomas of the colon - PubMed (original) (raw)

Pharmacokinetics and anti-tumour activity of LM985 in mice bearing transplantable adenocarcinomas of the colon

J A Double et al. Br J Cancer. 1986 Oct.

Free PMC article

Abstract

LM985 is one of a series of compounds based on the flavone ring structure and selected for clinical trial primarily for its activity in colon 38 as part of the NCI screen. We have investigated the anti-tumour activity against three differing transplantable adenocarcinomas of the mouse colon (MAC). Single i.p. injection at maximum tolerated dose showed no activity against the ascitic tumour MAC 15A, moderate activity against subcutaneous tumours MAC 13 and MAC 15A and produced a significant growth delay against MAC 26. These responses against s.c. tumours were considerably enhanced by repeated injection 7 days later when greater than 90% tumour inhibition was seen in MAC 13 and cures were achieved in MAC 26. Pharmacokinetic studies confirm the rapid degradation of LM985 to LM975, the possible active principle. Analysis of area under the curve for LM975 indicated a good relationship with administered doses of LM985 and tumour responses. The MAC system shows a good correlation with human large bowel cancer and these preliminary observations with LM985 would suggest that it or its metabolite LM975 may have a value in the management of large bowel cancer.

PubMed Disclaimer

Cited by

Professor Tom Connors and the development of novel cancer therapies by the Phase I/II Clinical Trials Committee of Cancer Research UK.
Newell DR, Searle KM, Westwood NB, Burtles SS; Cancer Research UK Phase I/II Clinical Trials Committee. Newell DR, et al. Br J Cancer. 2003 Aug 4;89(3):437-54. doi: 10.1038/sj.bjc.6601106. Br J Cancer. 2003. PMID: 12888809 Free PMC article. No abstract available.
Factors involved in the anti-cancer activity of the investigational agents LM985 (flavone acetic acid ester) and LM975 (flavone acetic acid).
Bibby MC, Double JA, Phillips RM, Loadman PM. Bibby MC, et al. Br J Cancer. 1987 Feb;55(2):159-63. doi: 10.1038/bjc.1987.32. Br J Cancer. 1987. PMID: 3814485 Free PMC article.
Unique chemosensitivity of MAC 16 tumours to flavone acetic acid (LM975, NSC 347512).
Bibby MC, Double JA, Loadman PM. Bibby MC, et al. Br J Cancer. 1988 Sep;58(3):341-4. doi: 10.1038/bjc.1988.215. Br J Cancer. 1988. PMID: 3179187 Free PMC article.
Experimental correlations of in vitro drug sensitivity with in vivo responses to ThioTEPA in a panel of murine colon tumours.
Phillips RM, Bibby MC, Double JA. Phillips RM, et al. Cancer Chemother Pharmacol. 1988;21(2):168-72. doi: 10.1007/BF00257366. Cancer Chemother Pharmacol. 1988. PMID: 3127072

Pharmacokinetics and anti-tumour activity of LM985 in mice bearing transplantable adenocarcinomas of the colon - PubMed (original) (raw)