Antineoplastic effect of orally administered 1-alkyl carbamoyl derivatives of 5-fluorouracil on sc implanted Lewis lung carcinoma and B16 melanoma.

The antitumor activity of 1-alkyl carbamoyl derivatives of 5-fluorouracil against Lewis lung carcinoma and B16 melanoma by long-term oral administration was examined. The 1-hexyl and 1-phenethyl carbamoyl-5-fluorouracil derviatives were markedly active against early Lewis lung carcinoma among the derivatives tested. These compounds were not markedly active against advanced Lewis lung carcinoma but did show acceptable activity. Increases in lifespan in mice with early Lewis lung carcinoma at optimal doses of 1-hexyl and 1-phenethyl carbamoxyl-5-fluorouracil were 98% and 78% respectively. In advanced Lewis lung carcinoma, the 1-hexyl derivative was active by either intermittent or daily administration, but the 1-phenethyl derivative was active only by daily administration. Lung metastases were not inhibited by optimal doses of the 1-hexyl derivative but were completely inhibited by the 1-phenethyl derivative. The 1-hexyl derivative was also active against B16 melanoma and the increase in lifespan at optimal doses was 27%. As a result, 1-hexyl carbamoyl-5-fluorouracil was found to be the most active derivative against early Lewis lung carcinoma and B16 melanoma. However, 1-phenethyl carbamoyl-5-fluorouracil was the most active derivative against advanced Lewis lung carcinoma by daily administration and this compound completely inhibited lung metastases, while 5-fluorouracil and cyclophosphamide did not inhibit lung metastases.