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Both coumarin (1,2-benzopyrone) and warfarin (4-hydroxycoumarin) have been shown to prevent the recurrence of malignant melanoma. Their action is macrophage-dependent and the dosage is critical. In 1984 a multicentre, prospective, randomised, double-blind trial of coumarin, given as a daily 50-mg dose for 2 years after surgery in patients with high-risk melanoma, was started. the patients had lesions greater than 1.70 mm thick and TNM stage IB or stage II disease. To date there are 4 recurrences in the coumarin-treated group of 13 patients, and 10 recurrences in the placebo-treated group of 14 patients (P0.01). There were no toxic effects.

The T lymphocytes populations of 22 young healthy adults, 21 healthy middle aged and older blood donors, 35 non-pregnant women of child bearing age and 14 patients with advanced malignant disease were assessed and compared. It was found that the mean T cell counts in the middle aged and older controls were significantly lower than in the healthy young adults and were further reduced in the patients with malignant disease. The addition of the proteolytic agent brinase (protease 1 obtained from Aspergillus oryzae) to the rosetting test increased the T cell counts signficantly in all groups. This was mot marked in the older age groups and the patients with malignant disease. The proteolytic agent is shown to exert its effect on the lymphocytes in the test. Slow intravenous infusion of either brinase or streptokinase into patients with malignant disease is shown to result in increased T lymphocyte counts pari passu with a restoration of skin allergy. The significance of these findings and possible mode of action of the proteolytic agents in increasing T cell activity are discussed.