The Pharmaceutical Journal
Vol 270 No 7250 p713
24 May 2003

This article
Reprint
Photocopy

News summary

Related websites
Bioenvision (www.bioenvision.co.uk)

Second mode of action suggested for trilostane in breast cancer

Clarification of the modes of action of trilostane (Modrenal) in breast cancer was given this week.

Speaking at a press briefing, Dr Chris Wood, chief executive of the drug's manufacturer, Bioenvision, explained that although trilostane has been licensed for use in advanced breast cancer for a number of years, data about how exactly the drug works have been needed. "Until now, it has not been widely used," he said.

Professor Gavin Vinson, professor of biochemistry at Queen Mary, University of London, said that trilostane inhibits breast cell proliferation through two pathways. The first, an oestrogen-dependent pathway, is already known about. However, he presented data on the discovery that a second pathway — a growth factor-dependent pathway — established a new mechanism of action for trilostane. This is mediated by trilostane acting at the binding site of a protein called AP1. "Trilostane blocks both pathways and this makes it a unique drug," he said.

Dr Wood presented the results of a meta-analysis of studies examining the efficacy of trilostane. Of a total of 714 post-menopausal women with advanced breast cancer, 35 per cent responded to trilostane treatment, 38 per cent did not respond and 28 per cent either stopped treatment early or died.

Dr Wood recommended that trilostane should be used in postmenopausal women with advanced breast cancer after treatment with tamoxifen and aromatase inhibitors.

Dr Rob Stein, a consultant in medical oncology at University College London Hospitals NHS Trust, was cautious about trilostane's use. The evidence discussed at the press briefing raised questions that were worth further investigation but "my suspicion is that it will not prove terribly useful", he said. He believes evidence to support use of trilostane is currently incomplete.

In particular, he raised two points. "It is an inconvenient drug to give and I suspect it is not hugely efficacious." Some of the difficulties with trilostane include its side effect profile, the need for concomitant corticosteroids replacement and the fact the multiple doses are needed each day.