Summary
1-Hexylcarbamoyl-5-fluorouracil (HCFU) and its parent compount 5-fluorouracil (5-FU) were tested PO for antitumor activity against mouse colon adenocarcinoma 26 (colon 26), colon adenocarcinoma 38 (colon 38), and Lewis lung carcinoma. The drugs were given orally at 2–4 days intervals for a total of ten doses. 5-FU was moderately active against colons 26 and 38 but not against Lewis lung carcinoma. In this treatment regiment the most impressive antitumor activity was obtained with HCFU against colons 26 and 38, especially colon 38 tumor. At 300 mg HCFU/kg, one out of seven mice inoculated with colon 26 and five out of ten mice inoculated with colon 38 became tumor-free. HCFU, however, was marginally effective in the prolongation of survival time of mice bearing Lewis lung carcinoma.
5-FU is approximately twice as active as HCFU against cultured cell lines from colon 26, colon 38, and Lewis lung carcinoma. Lewis lung carcinoma cells were most sensitive against HCFU, which is in contrast to the results obtained in the in vivo experiment. The IC50 value of HCFU against Lewis lung carcinoma cells was approximately half that against colon 26 and colon 38 cells. This higher sensitivity of Lewis lung cells against HCFU could be explained by the higher cellular uptake of the drug.
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Corbett TH, Griswold DP, Roberts BJ, Peckham J, Schabel FM, Jr (1975) A mouse colon-tumor model for experimental therapy. Cancer Chemother Rep [2] 5:169
Corbett TH, Griswold DP Jr, Roberts BJ, Peckham JC, Schabel FM, Jr (1977) Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer 40:2660
Hahn RG, Moertel CG, Schutt A, Bruckner HW (1975) A double-blind comparison of intensive course of 5-fluorouracil by oral vs. intravenous route in the treatment of corolectal carcinoma. Cancer 35:1031
Hoshi A, Iigo M, Yoshida M, Kuretani K (1976) Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in a variety of experimental tumors. Gann 67:725
Hoshi A, Iigo M, Nakamura A, Inomata M, Kuretani K (1978) Antitumor activity of 1-alkylcarbamoyl derivatives of 5-fluorouracil against L1210 leukemia. Chem Pharm Bull (Tokyo) 26:161
Iigo M, Hoshi A, Nakamura A, Kuretani K (1978a) Antitumor activity of 1-alkylcarbamoyl derivatives of 5-fluorouracil in a variety of mouse tumors. Cancer Chemother Pharmacol 1:203
Iigo M, Hoshi A, Nakamura A, Kuretani K (1978b) Antitumor activity of 1-hexylcarbamoyl-5-fluorouracil in Lewis lung carcinoma and B16 melanoma. J Pharm Dyn 1:49
Ishimura K, Koizumi S, Inoue H, Dotawa T, Karakama T, Yoshikawa K, Kimura S, Mori H, Sawai M (1979a) Toxicological study on 1-hexylcarbamoyl-5-fluorouracil (HCFU). I. Subacute and chronic toxicity studies in rats. Pharmacometrics (Tokyo) 17:575
Ishimura K, Koizumi S, Neda K, Inoue H, Kobe H, Sato H, Sato K, Niyokawa H, Sawai M (1979b) Toxicological study on 1-hexylcarbamoyl-5-fluorouracil (HCFU). II. Subacute and chronic toxicity studies in dogs. Pharmacometrics (Tokyo) 17:597
Karrer K, Humphreys SR (1967) Continuous and limited cources of cylophosphamide (NSC-26271) in mice with pulmonary metastasis after surgery. Cancer Chemother Rep 51:439
Klein G (1961) Population changes and drug resistance in tumors. In: Biological approaches to cancer chemotherapy. Academic Press, London, p 201
Mayo JG, Laster WR, Andrews CM (1972) Success and failure in the treatment of solid tumors. III. ‘Cure’ of metastatic Lewis lung carcinoma with methyl-CCNU (NSC-95441) and surgery-chemotherapy. Cancer Chemother Rep 56:183
Ozaki S, Ike Y, Mizuno H, Ishikawa K, Mori H (1977) 5-Fluorouracil derivatives. I. The synthesis of 1-carbamoyl-5-fluorouracils. Bull Chem Soc Jpn 50:2406
Tsuruo T, Iida H, Tsukagoshi S, Sakurai Y (1979) Comparison of cytotoxic effect and cellular uptake of 1-β-d-arabinofuranosyl-cytosine and its N 4-acyl-derivatives, using cultured KB cells. Cancer Res 39:1063
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Tsuruo, T., Iida, H., Naganuma, K. et al. Inhibition of murine colon adenocarcinomas and Lewis lung carcinoma by 1-hexylcarbamoyl-5-fluorouracil. Cancer Chemother. Pharmacol. 4, 83–87 (1980). https://doi.org/10.1007/BF00254027
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DOI: https://doi.org/10.1007/BF00254027