New Cancer Drug Shown To Be Active In Patients For The First Time

A drug which blocks the action of a naturally occurring enzyme has, for the first time, shown activity in patients with cancer, according to UK researchers reporting online in The Lancet Oncology. "We have shown in vivo in patients with cancer that nitric oxide has a role in maintaining tumour blood supply, and we provide early clinical evidence that inhibition of nitric-oxide synthesis has tumour anti-vascular activity" says lead author Prof Peter Hoskin (Mount Vernon Cancer Centre, Middlesex, UK).

Maintenance of the blood supply to tumours is essential if these cell masses are to continue dividing and growing. Several studies in animals have suggested that enzymes involved in the synthesis of nitric oxide might play a role in maintaining this blood supply. Drugs which block the nitric oxide synthase enzymes have therefore been proposed as potential anticancer agents. The study authors assessed the effect of the nitric oxide synthase blocker, N-nitro-L-arginine (L-NNA), on tumour blood volume in 18 patients with various cancers enrolled on a dose-escalation phase I study.

In 8 patients given the higher doses of the drug L-NNA, imaging scans showed that tumour blood volume decreased significantly 1 h after administration of the drug and that this decrease was maintained at 24 h. Furthermore, there was a significant correlation between concentrations of L-NNA in the patients' blood and the reduction in tumour blood volume at 24 h, providing further supporting evidence of the drug's anti-vascular activity.

First author Dr Quan-Sing Ng (Mount Vernon Cancer Centre, Middlesex, UK) states: "the sustained reductions in tumour blood volume seen in all patients after just a single dose of L-NNA is exciting, and there is potential for its use as a novel vascular targeting agent in the treatment of cancer. This study provides support for further development of this agent in clinical trials".

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Contact: Prof Peter J Hoskin. Marie Curie Research Wing, Mount Vernon Cancer Centre, Rickmansworth Road, Middlesex, HA6 2RN, UK.

Contact: Lancet press office
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