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Cyclocreatine in cancer chemotherapy.

Publication ,  Journal Article
Teicher, BA; Menon, K; Northey, D; Liu, J; Kufe, DW; Kaddurah-Daouk, R
Published in: Cancer Chemother Pharmacol
1995

Cyclocreatine, an analog of creatine, is an efficient substrate for creatine kinase, but its phosphorylated form is a poor phosphate donor in comparison with creatine phosphate. Cyclocreatine was not very cytotoxic upon 24 h of exposure of human SW2 small-cell lung cancer cells to concentrations of up to 5 mM. However, combinations of cyclocreatine (0.5 mM, 24 h) with each of four antitumor alkylating agents, cis-diamminedichloroplatinum(II), melphalan, 4-hydroperoxycyclophosphamide, and carmustine, resulted in additive to greater-than-additive cytotoxicity toward exponentially growing SW2 cells. The greatest levels of synergy were seen at higher concentrations of 4-hydroperoxycyclophosphamide and carmustine as determined by isobologram analysis. In vivo cyclocreatine (0.5 or 1 g/kg) was more effective if given i.v. rather than i.p. The longest tumor-growth delays, up to 10 days, were produced by extended regimens of cyclocreatine. Cyclocreatine was an effective addition to therapy with standard anticancer agents including cis-diamminedichloroplatinum(II), cyclophosphamide, Adriamycin, or 5-fluorouracil. No additional toxicity was observed when 10 days of cyclocreatine treatment was given with full standard-dose regimens of each drug. The resultant increases in tumor-growth delay were 1.7- to 2.4-fold as compared with those obtained for each of the drugs alone. These results indicate that cyclocreatine may be an effective single agent and an effective addition to combination chemotherapy regimens.

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Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1995

Volume

35

Issue

5

Start / End Page

411 / 416

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Melphalan
  • Mammary Neoplasms, Experimental
  • Lung Neoplasms
  • Injections, Intravenous
  • Injections, Intraperitoneal
  • Humans
 

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Teicher, B. A., Menon, K., Northey, D., Liu, J., Kufe, D. W., & Kaddurah-Daouk, R. (1995). Cyclocreatine in cancer chemotherapy. Cancer Chemother Pharmacol, 35(5), 411–416. https://doi.org/10.1007/s002800050255
Teicher, B. A., K. Menon, D. Northey, J. Liu, D. W. Kufe, and R. Kaddurah-Daouk. “Cyclocreatine in cancer chemotherapy.Cancer Chemother Pharmacol 35, no. 5 (1995): 411–16. https://doi.org/10.1007/s002800050255.
Teicher BA, Menon K, Northey D, Liu J, Kufe DW, Kaddurah-Daouk R. Cyclocreatine in cancer chemotherapy. Cancer Chemother Pharmacol. 1995;35(5):411–6.
Teicher, B. A., et al. “Cyclocreatine in cancer chemotherapy.Cancer Chemother Pharmacol, vol. 35, no. 5, 1995, pp. 411–16. Pubmed, doi:10.1007/s002800050255.
Teicher BA, Menon K, Northey D, Liu J, Kufe DW, Kaddurah-Daouk R. Cyclocreatine in cancer chemotherapy. Cancer Chemother Pharmacol. 1995;35(5):411–416.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

1995

Volume

35

Issue

5

Start / End Page

411 / 416

Location

Germany

Related Subject Headings

  • Tumor Cells, Cultured
  • Rats, Inbred F344
  • Rats
  • Oncology & Carcinogenesis
  • Melphalan
  • Mammary Neoplasms, Experimental
  • Lung Neoplasms
  • Injections, Intravenous
  • Injections, Intraperitoneal
  • Humans