Slow, but sure

A gentle therapy for patients undergoing chemotherapy

Published: Sunday 31 December 2000

when cancer patients cannot withstand strong doses of chemotherapy, oncologists try out a gentler method -- low oral doses taken continuously. This method is welcomed by many patients because it has less side-effects. Unfortunately, this approach sometimes does not stop the cancerous growth. Which is why it cannot be applied widely enough in cancer control. In addition, not much is known about the mode of action of this 'gentle therapy' especially when it comes to slowing down the growth of tumours that have already developed resistance to drugs.

Two studies, just published, attempt to answer some of the vexing questions. The first study is from the laboratory of the celebrated cancer researcher Judah Folkman and his team at the Harvard School of Medicine, Boston, usa ( Cancer Research , Vol 60, No 7). The other is a Canadian study by Giannoula Klement and Robert Kerbel of the University of Toronto, Canada ( Journal of Clinical Investigation , Vol 105, No 8). Both teams tried out this gentle therapy also called 'metronomic therapy' as it never misses a beat. Their aim was to block angiogenesis -- the process of sprouting new blood vessels that feed the ever-growing cancerous cells. The two studies have concluded that the efficacy of metronomic therapy is enhanced when used in combination with drugs that specifically inhibit angiogenesis.

Folkman's team found why standard chemotherapy, which kills dividing cells, does not block angiogenesis by killing endothelial cells that divide to form new blood vessels. It appears that the break period offered by the intermittent chemotherapy gives sufficient time for the endothelial cells to recover and restore blood supply to the growing tumours. Their solution -- eliminate the rest period. Both teams injected mice with cancerous cells including some tumours that are highly-resistant to the drugs. They found that continuous treatment with relatively low doses of drugs caused the tumours to slow down in their growth and shrink.

However, the tumours eventually grew again. The Harvard team then added a drug, tnp -450, which is anti-angiogenic The tumours did not return even after the treatment was discontinued. Their treatment apparently kills endothelial cells and blocks angiogenesis. The results showed that not only was the treatment effective in curing the animals of the cancer, but was also non-toxic.

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