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Cyclophosphamide and dimethylsulfoxide in the treatment of squamous carcinoma of the lung

Therapeutic efficacy, toxicity, and pharmacokinetics

  • Original Articles
  • Cyclophosphamide Dimethylsulfoxide Squamous Lung Carcinoma
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Summary

To determine whether dimethylsulfoxide (DMSO) can potentiate antitumor activity of cyclophosphamide (CYC) in patients with squanmous cell carcinoma of the lung, 14 patients were treated with 5 l of a 5% or 6% DMSO solution PO over 3 days and 1,500 mg CYC/m2 IV as a 60-min infusion on the third day of treatment. Serial blood, CSF, and urine samples were collected to assess the pharmacokinetics of CYC. Courses were repeated every 3–4 weeks. No antitumor responses were observed. Toxicity was mainly hematologic and similar to that of CYC alone. There was one death from infection during granulocytopenia. Nonhematologic toxicity was moderate to severe and included nausea (14 patients) and vomiting (five patients). The plasma pharmacokinetics of CYC in this study are similar to previously reported results for CYC alone, but the 24-h urinary excretion of CYC in our study is much lower than previously reported. Further studies in tumors more responsive to CYC may be warranted.

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References

  1. Bagley CM Jr, Bostick FW, DeVita VT Jr (1973) Clinical pharmacology of cyclophosphamide. Cancer Res 33: 226

    Google Scholar 

  2. Bodey GP, Lagakos SW, Gutierrez AC, Wilson HE, Selawry OS (1977) Therapy for advanced squamous carcinoma of the lung. Cyclophosphamide versus “COMB”. Cancer 39: 1026

    Google Scholar 

  3. Brock N, Gross R, Hohorst HJ, Klein HO, Schneider B (1979) Activation of cyclophosphamide in man and animals. Cancer 27: 1512

    Google Scholar 

  4. Cohen JL, Lao JY, Jusko WJ (1971) Pharmacokinetics of cyclophosphamide in man. Br J Pharmacol 43: 677

    Google Scholar 

  5. Cornejo-Garrido J, Escobar-Lagos R (1975) Dimethylsulfoxide therapy as toxicity reducing agent and potentiation of cyclophosphamide in the treatment of different types of cancer. Ann NY Acad Sci 243: 412

    Google Scholar 

  6. D'Incalci M, Bolis G, Facchinetti T, Mangioni C, Morascol L, Morazzoni P, Salmona M (1979) Decreased half-life of cyclophosphamide in patients under continual treatment. Eur J Cancer 19: 7

    Google Scholar 

  7. Friedman OM, Boger E (1961) Colorimetric estimation of nitrogen mustards in aqueous media. Anal Chem 33: 906

    Google Scholar 

  8. Grochow LB, Colvin OM (1979) Clinical pharmacokinetics of cyclophosphamide. Clin Pharmacokinet 4: 380

    CAS  PubMed  Google Scholar 

  9. Jacob SW, Herschler R (eds) (1967) Dimethylsulfoxide. Ann NY Acad Sci 141: 1

  10. Jacob SW, Herschler R (1975) Biological actions of dimethylsulfoxide. Ann NY Acad Sci 243: 5

    Google Scholar 

  11. Jardine I, Fenselau C, Appler M, Kan MN, Brundrett RB, Colvin M (1978) Quantitation by gas chromatography-chemical ionization mass spectrometry of cyclophosphamide, phosphoramide mustard, and nornitrogen mustard in the plasma and urine of patients receiving cyclophosphamide therapy. Cancer Res 38: 408

    Google Scholar 

  12. Juma FD, Rogers KJ, Trounce JR, Brodbook JD (1978) Pharmacokinetics of intravenous cyclophosphamide in man estimated by gas-liquid chromatography. Cancer Chemother Pharmacol 1: 229

    Google Scholar 

  13. Juma FD, Rogers JH, Trounce JR (1979) Pharmacokinetics of cyclophosphamide and alkylating activity in man after intravenous and oral administration. Br J Clin Pharmacol 8: 209

    Google Scholar 

  14. Leak CD (ed) (1967) Biological actions of dimethylsulfoxide. Ann NY Acad Sci 141: 1

  15. Livingston RB, Einhorn L, Bodey GP, Burguess MA, Freireich EJ, Gottlieb JA (1975) COMB (cyclophosphamide, oncoving, methyl CCNU and bleomycin): A four-drug combination in solid tumors. Cancer 36: 327

    Google Scholar 

  16. Livingston RB, Fee WB, Einhorn LH, Burgess MA, Freireich EJ, Gottlieb JA, Farber MW (1976) BACON (bleomycin, adriamycin, CCNU, oncovin, and nitrogen mustard) in squamous lung cancer: Experience in 50 patients. Cancer 37: 1237

    Google Scholar 

  17. Livingston RB, Heilbrun L, Lehane D, Costanzi JJ, Bottomley R, Palmer RL, Stuckey WJ, Hoostraten B (1977) Comparative trial of combination chemotherapy in extensive squamous carcinoma of the lung: A Southwest Oncology Group study. Cancer Treat Rep 61: 1623

    Google Scholar 

  18. Mendelson D, Block JB, Serpick AA (1970) Effect of large intermittent intravenous doses of cyclophosphamide in lymphoma. Cancer 25: 715

    Google Scholar 

  19. Mouridsen HT, Faber O, skovsted L (1974) The biotransformation of cyclophosphamide in man: Analysis of the variation in normal subjects. Acta Pharmacol Toxicol (Kbh) 35: 98

    Google Scholar 

  20. National Academy of Science (1973) Dimethylsulfoxide as a therapeutic agent. National Academy of Science, Washington

    Google Scholar 

  21. Selawry PS (1974) The role of chemotherapy in the tretment of lung cancer. Semin Oncol 1: 259

    Google Scholar 

  22. Stanley EK (1980) Prognostic factors for survival in patients with inoperable lung cancer. J Natl Cancer Inst 65: 25

    CAS  PubMed  Google Scholar 

  23. Takita H, Marabella PC, Edgerton F, Rizzo D (1979) cis-Diamminedichloroplatinum, adriamycin, cyclophosphamide, CCNU, and vincristine in non-small cell lung carcinoma: A preliminary report. Cancer Treat Rep 63: 29

    Google Scholar 

  24. Warren, J, Sacsteder MR, Jarose H, Wasserman B, Andreotti PE (1975) Potentiation of antineoplastic compounds by oral dimethylsulfoxide in tumor bearing rates. Ann NY Acad Sci 243: 194

    Google Scholar 

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Fuks, J.Z., Egorin, M.J., Aisner, J. et al. Cyclophosphamide and dimethylsulfoxide in the treatment of squamous carcinoma of the lung. Cancer Chemother. Pharmacol. 6, 117–120 (1981). https://doi.org/10.1007/BF00262327

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  • DOI: https://doi.org/10.1007/BF00262327

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