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

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.