Skip to main content
NCBI home page
British Journal of Cancer logoLink to British Journal of Cancer
. 1995 Mar;71(3):598–604. doi: 10.1038/bjc.1995.116

Factors affecting platinum concentrations in human surgical tumour specimens after cisplatin.

D J Stewart 1, J M Molepo 1, R M Green 1, V A Montpetit 1, H Hugenholtz 1, A Lamothe 1, N Z Mikhael 1, M D Redmond 1, M Gadia 1, R Goel 1
PMCID: PMC2033659  PMID: 7880744

Abstract

We assessed factors which affect cisplatin concentrations in human surgical tumour specimens. Cisplatin 10 mg m-2 was given i.v. to 45 consenting patients undergoing surgical resection of neoplasms, and platinum was assayed in resected tumour and in deproteinated plasma by flameless atomic absorption spectrophotometry. By multiple stepwise regression analysis of normalised data, patient characteristics that emerged as being most closely associated (P < 0.05) with tumour platinum concentrations (after correcting for associations with other variables) were tumour 'source' [primary brain lymphomas, medulloblastomas and meningiomas ('type LMM') > 'others' > lung cancer > head/neck cancer > gliomas) or tumour 'type' (LMM > brain metastases > extracerebral tumours > gliomas), serum calcium and chloride (positive correlations) and bilirubin (negative). Tumour location (intracranial vs extracranial) did not correlate with platinum concentrations. If values for a single outlier were omitted, high-grade gliomas had significantly higher platinum concentrations (P < 0.003) than low-grade gliomas. For intracranial tumours, the computerised tomographic scan feature that correlated most closely with platinum concentrations in multivariate analysis was the darkness of peritumoral oedema. Tumour source or type is a much more important correlate of human tumour cisplatin concentrations than is intracranial vs extracranial location. Serum calcium, chloride and bilirubin levels may affect tumour cisplatin uptake or retention. CT scan characteristics may help predict cisplatin concentrations in intracranial tumours.

Full text

PDF
598

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Berry J. P., Pauwells C., Tlouzeau S., Lespinats G. Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma. Cancer Res. 1984 Jul;44(7):2864–2868. [PubMed] [Google Scholar]
  2. Blasberg R. G., Groothuis D. R. Chemotherapy of brain tumors: physiological and pharmacokinetic considerations. Semin Oncol. 1986 Mar;13(1):70–82. [PubMed] [Google Scholar]
  3. Dedrick R. L., Zaharko D. S., Bender R. A., Bleyer W. A., Lutz R. J. Pharmacokinetic considerations on resistance to anticancer drugs. Cancer Chemother Rep. 1975 Jul-Aug;59(4):795–804. [PubMed] [Google Scholar]
  4. Feun L. G., Yung W. K., Stewart D. J., Savaraj N., Bodey G. P. Phase II trial of mitogauzone in malignant primary brain tumors. Cancer Treat Rep. 1985 Mar;69(3):329–330. [PubMed] [Google Scholar]
  5. Gaffin S. L. Rapid solubilization of human body tissues and tissue fluids for microdetermination of heavy metals. Clin Toxicol. 1979 Oct;15(3):293–300. doi: 10.3109/15563657908989880. [DOI] [PubMed] [Google Scholar]
  6. Groothuis D. R., Fischer J. M., Vick N. A., Bigner D. D. Comparative permeability of different glioma models to horseradish peroxidase. Cancer Treat Rep. 1981;65 (Suppl 2):13–18. [PubMed] [Google Scholar]
  7. Gross R. B., Scanlon K. J. Amino acid membrane transport properties of L1210 cells resistant to cisplatin. Chemioterapia. 1986 Feb;5(1):37–43. [PubMed] [Google Scholar]
  8. Hasegawa H., Ushio Y., Hayakawa T., Yamada K., Mogami H. Changes of the blood-brain barrier in experimental metastatic brain tumors. J Neurosurg. 1983 Aug;59(2):304–310. doi: 10.3171/jns.1983.59.2.0304. [DOI] [PubMed] [Google Scholar]
  9. Kantarjian H., Farha P. A., Spitzer G., Murphy W. K., Valdivieso M. Systemic combination chemotherapy as primary treatment of brain metastasis from lung cancer. South Med J. 1984 Apr;77(4):426–430. doi: 10.1097/00007611-198404000-00005. [DOI] [PubMed] [Google Scholar]
  10. Kelley S. L., Rozencweig M. Resistance to platinum compounds: mechanisms and beyond. Eur J Cancer Clin Oncol. 1989 Aug;25(8):1135–1140. doi: 10.1016/0277-5379(89)90405-7. [DOI] [PubMed] [Google Scholar]
  11. Kolarić K., Roth A., Jelicić I., Matković A. Preliminary report on antitumorigenic activity of cis-dichlorodiamine platinum in metastatic brain tumors. Tumori. 1981 Oct 31;67(5):483–486. doi: 10.1177/030089168106700515. [DOI] [PubMed] [Google Scholar]
  12. Levin V. A., Clancy T. P., Ausman J. I., Rall D. P. Uptake and distribution of 3 H-methotrexate by the murine ependymoblastoma. J Natl Cancer Inst. 1972 Apr;48(4):875–883. [PubMed] [Google Scholar]
  13. Levin V. A., Freeman-Dove M., Landahl H. D. Permeability characteristics of brain adjacent to tumors in rats. Arch Neurol. 1975 Dec;32(12):785–791. doi: 10.1001/archneur.1975.00490540029003. [DOI] [PubMed] [Google Scholar]
  14. Loo J. C., Riegelman S. Assessment of pharmacokinetic constants from postinfusion blood curves obtained after I.V. infusion. J Pharm Sci. 1970 Jan;59(1):53–55. doi: 10.1002/jps.2600590107. [DOI] [PubMed] [Google Scholar]
  15. Mann S. C., Andrews P. A., Howell S. B. Short-term cis-diamminedichloroplatinum(II) accumulation in sensitive and resistant human ovarian carcinoma cells. Cancer Chemother Pharmacol. 1990;25(4):236–240. doi: 10.1007/BF00684878. [DOI] [PubMed] [Google Scholar]
  16. Neuwelt E. A., Maravilla K. R., Frenkel E. P., Barnett P., Hill S., Moore R. J. Use of enhanced computerized tomography to evaluate osmotic blood-brain barrier disruption. Neurosurgery. 1980 Jan;6(1):49–56. doi: 10.1227/00006123-198001000-00007. [DOI] [PubMed] [Google Scholar]
  17. Rosner D., Nemoto T., Pickren J., Lane W. Management of brain metastases from breast cancer by combination chemotherapy. J Neurooncol. 1983;1(2):131–137. doi: 10.1007/BF00182958. [DOI] [PubMed] [Google Scholar]
  18. Rowe-Jones D. C. Cytotoxic penetration and concentration in human malignant tumours. Br J Surg. 1969 Oct;56(10):774–778. doi: 10.1002/bjs.1800561021. [DOI] [PubMed] [Google Scholar]
  19. Shumaker R. C. PKCALC: a BASIC interactive computer program for statistical and pharmacokinetic analysis of data. Drug Metab Rev. 1986;17(3-4):331–348. doi: 10.3109/03602538608998295. [DOI] [PubMed] [Google Scholar]
  20. Stewart D. J. A critique of the role of the blood-brain barrier in the chemotherapy of human brain tumors. J Neurooncol. 1994;20(2):121–139. doi: 10.1007/BF01052723. [DOI] [PubMed] [Google Scholar]
  21. Stewart D. J., Benjamin R. S., Luna M., Feun L., Caprioli R., Seifert W., Loo T. L. Human tissue distribution of platinum after cis-diamminedichloroplatinum. Cancer Chemother Pharmacol. 1982 Dec;10(1):51–54. doi: 10.1007/BF00257239. [DOI] [PubMed] [Google Scholar]
  22. Stewart D. J., Dulberg C., Molepo J. M., Mikhael N. Z., Montpetit V. A., Redmond M. D., Goel R. Factors affecting human autopsy kidney-cortex and kidney-medulla platinum concentrations after cisplatin administration. Cancer Chemother Pharmacol. 1994;34(1):14–22. doi: 10.1007/BF00686106. [DOI] [PubMed] [Google Scholar]
  23. Stewart D. J., Grahovac Z., Hugenholtz H., Russell N. A., Richard M. T., Benoit B. G., Riding M. D., Danjoux C., Maroun J. A. Intraarterial mitomycin-C for recurrent brain metastases. Am J Clin Oncol. 1987 Oct;10(5):432–436. doi: 10.1097/00000421-198710000-00013. [DOI] [PubMed] [Google Scholar]
  24. Stewart D. J., Maroun J. A., Verma S., Perrault D., Earhart R. H. Phase I study of weekly intravenous administration of menogaril to adults with solid tumors. Am J Clin Oncol. 1989 Dec;12(6):511–518. doi: 10.1097/00000421-198912000-00011. [DOI] [PubMed] [Google Scholar]
  25. Stewart D. J., Molepo J. M., Eapen L., Montpetit V. A., Goel R., Wong P. T., Popovic P., Taylor K. D., Raaphorst G. P. Cisplatin and radiation in the treatment of tumors of the central nervous system: pharmacological considerations and results of early studies. Int J Radiat Oncol Biol Phys. 1994 Jan 15;28(2):531–542. doi: 10.1016/0360-3016(94)90082-5. [DOI] [PubMed] [Google Scholar]
  26. Stewart D. J. The role of chemotherapy in the treatment of gliomas in adults. Cancer Treat Rev. 1989 Sep;16(3):129–160. doi: 10.1016/0305-7372(89)90007-8. [DOI] [PubMed] [Google Scholar]
  27. Stewart D. J., Verma S., Maroun J. A., Robillard L., Earhart R. H. Phase I study of oral menogaril administered on a once weekly schedule. Invest New Drugs. 1990 Feb;8(1):43–52. doi: 10.1007/BF00216923. [DOI] [PubMed] [Google Scholar]
  28. Stewart P. A., Hayakawa K., Farrell C. L., Del Maestro R. F. Quantitative study of microvessel ultrastructure in human peritumoral brain tissue. Evidence for a blood-brain barrier defect. J Neurosurg. 1987 Nov;67(5):697–705. doi: 10.3171/jns.1987.67.5.0697. [DOI] [PubMed] [Google Scholar]
  29. Tator C. H. Retention of tritiated methotrexate in a transplantable mouse glioma. Cancer Res. 1976 Sep;36(9 PT1):3058–3066. [PubMed] [Google Scholar]
  30. Tchang S., Scotti G., Terbrugge K., Melancon D., Baelanger G., Milner C., Ethier R. Computerized tomography as a possible aid to histological grading of supratentorial gliomas. J Neurosurg. 1977 Jun;46(6):735–739. doi: 10.3171/jns.1977.46.6.0735. [DOI] [PubMed] [Google Scholar]
  31. Timmer-Bosscha H., Hospers G. A., Meijer C., Mulder N. H., Muskiet F. A., Martini I. A., Uges D. R., de Vries E. G. Influence of docosahexaenoic acid on cisplatin resistance in a human small cell lung carcinoma cell line. J Natl Cancer Inst. 1989 Jul 19;81(14):1069–1075. doi: 10.1093/jnci/81.14.1069. [DOI] [PubMed] [Google Scholar]
  32. Vermorken J. B., van der Vijgh W. J., Klein I., Gall H. E., van Groeningen C. J., Hart G. A., Pinedo H. M. Pharmacokinetics of free and total platinum species after rapid and prolonged infusions of cisplatin. Clin Pharmacol Ther. 1986 Feb;39(2):136–144. doi: 10.1038/clpt.1986.24. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES