Pharmaceutisch Weekblad

, Volume 7, Issue 4, pp 125–133 | Cite as

Predictive testing in cancer chemotherapy

II. In vitro
  • P. H. Th. J. Slee
  • A. T. van Oosterom
  • E. A. de Bruijn
Review Articles


During the last thirty years severalin vitro techniques have been developed to predict sensitivity of individual tumours. When the results of these techniques were correlated with the clinical response in larger groups of patients, the accuracy for predicting resistance was greater than for predicting sensitivity. Amongst the culture techniques the colony-forming assays have received much attention. Research with tumour cell lines and the sound biological basis do support this preference on other techniques. Studies on these assays have come from several independent laboratories, who report comparable results. Improvement of the culture technique and more insight into thein vitro pharmacology is needed, before application on wider scale is justified. Colony-forming culture techniques have not only been propagated for individualized chemotherapy, but also for drug screening. New antitumour agents and analogues can be screened in a short time for their sensitivity in many histologic tumour types.


Public Health Tumour Cell Internal Medicine Clinical Response Comparable Result 
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  1. 1.
    Slee PHThJ, Van Oosterom AT, De Bruijn EA. Predictive testing in cancer chemotherapy. vivo. Pharm Weekbl [Sci] 1985;7:93–9.Google Scholar
  2. 2.
    Cobb JP. Tissue culture observations of the effects of chemotherapeutic agents on human tumors. Trans NY Acad Sci 1955;17:237–49.Google Scholar
  3. 3.
    Wright JEC, Plummer-Cobb J, Gumport SL, Safadi D, Walker DG, Galomb FM. Further investigations of the relation between the clinical and tissue culture response to chemotherapeutic agents on human cancer. Cancer 1962;15:284–93.PubMedGoogle Scholar
  4. 4.
    Seibert K, Lippman M. Hormone Receptors in Breast Cancer. Clin Oncol 1982;1:735–79.Google Scholar
  5. 5.
    Levine RM, Lippman ME. Relationship Between Estrogen-Receptor Proteins and Response to Chemotherapy in Breast Cancer. Cancer Treat Rep 1984;68:573–6.PubMedGoogle Scholar
  6. 6.
    Hurley JD, Yount LJ. Selection of Anticancer Drugs for Palliation Using Tissue Culture Sensitivity Studies. Am J Surg 1965;109:39–42.PubMedGoogle Scholar
  7. 7.
    Tanneberger St, Bacigalupo G. Einige Erfahrungen mit der individuellen zytostatischen Behandlung maligner Tumoren nach prätherapeutischer Zytostatika-sensibilitätsprüfungin vitro (Onkobiogramm). Arch Geschwulstforsch 1970;35:44–53.PubMedGoogle Scholar
  8. 8.
    Weisenthal LM, Marsden JA, Dill PL, Macaluso CK. A Novel Dye Exclusion Method for Testingin vitro Chemosensitivity of Human Tumors. Cancer Res 1983;43:749–57.PubMedGoogle Scholar
  9. 9.
    DiPaolo JA. Analysis of an Individual Chemotherapy Assay System. Natl Cancer Inst Monogr 1971;34:240–5. assay for testing tumour sensitivity and clinical applications. Drugs Exp Clin Res 1982;8:345–58.PubMedGoogle Scholar
  10. 11.
    Daidone MG, Silvestrini R, Sanfilippo O. Clinical relevance of anin vitro antimetabolite assay for monitoring human tumour chemosensitivity. In: Salmon SE, Jones SE, eds. Adjuvant Therapy of Cancer III. New York: Grune and Stratton, 1982:25–32.Google Scholar
  11. 12.
    Salmon SE, Alberts DS, Meyskens FL, et al. Clinical Correlations ofIn vitro Drug Sensitivity. In: Salmon SE, ed. Cloning of human tumor stem cells. New York: Alan R. Liss Inc., 1980:223–45.Google Scholar
  12. 13.
    Von Hoff DD, Casper J, Bradley E, Sandbach J, Jones D, Makuch R. Association Between Human Tumor Colony-Forming Assay Results and Response of An Individual Patients Tumor to Chemotherapy. Am J Med 1981:70:1027–32.CrossRefPubMedGoogle Scholar
  13. 14.
    Von Hoff DD, Clark GM, Stogdill BJ, et al. Prospective Clinical Trial of a Human Tumor Cloning System. Cancer Res 1983:43:1926–31.PubMedGoogle Scholar
  14. 15.
    Bertelsen CA, Sondak VK, Mann BD, Korn EL, Kern DH. Chemosensitivity Testing of Human Solid Tumors. A Review of 1582 Assays With 258 Clinical Correlations. Cancer 1984;53:1240–5.PubMedGoogle Scholar
  15. 16.
    Von Hoff DD, Weisenthal L.In Vitro Methods to Predict for Patient Response to Chemotherapy. Adv Pharmacol Chemother 1980;17:133–56.PubMedGoogle Scholar
  16. 17.
    Dendy PP, Dawson MPA, Warner DMA, Honess DJ. Quantitative Assays ofin vitro Drug Damage. In: Dendy PP, ed. Human tumours in short term culture. Techniques and clinical Applications. London: Academic Press, 1976:139–49.Google Scholar
  17. 18.
    Roper PR, Drewinko B. Comparison ofin vitro Methods to Determine Drug-induced Cell Lethality. Cancer Res 1976;36:2182–8.PubMedGoogle Scholar
  18. 19.
    Durkin WJ, Ghanta VK, Balch CM, Davis WD, Hiramoto RN. A Methodological Approach to the Prediction of Anticancer Drug Effect in Humans. Cancer Res 1979;39:402–7.PubMedGoogle Scholar
  19. 20.
    Weisenthal LM, Marsden JA, Dill PL, Macaluso CK. A novel dye exclusion method for testingin vitro chemosensitivity of human tumors. Cancer Res 1983;43:402–7.Google Scholar
  20. 21.
    Dickson JA, Suzanger M.In vitro sensitivity testing of human tumour slices to chemotherapeutic agents. Its place in cancer therapy. In: Dendy PP, ed. Human Tumours in Short Term Culture. London: Academic Press, 1976:107–38.Google Scholar
  21. 22.
    Black MM, Speer FD. Further Observations on the Effects of Cancer Chemotherapeutic Agents on thein Vitro Dehydrogenase Activity of Cancer Tissue. J Natl Cancer Inst 1954;14:1147–58.PubMedGoogle Scholar
  22. 23.
    Volm M, Wayss K, Kaufmann M, Mattern J. Pretherapeutic detection of tumour resistance and the results of tumour chemotherapy. Eur J Cancer 1979;15:983–93.PubMedGoogle Scholar
  23. 24.
    Freshney RI, Sherry A, Kane IM. Assay of anticancer drugs in tissue culture: conditions affecting their ability to incorporate3H-leucine after drug treatment. Br J Cancer 1975;31:89–99.PubMedGoogle Scholar
  24. 25.
    Yarnell M, Ambrose EJ, Shepley K, Tchao R. Drug assays on organ culture of biopsies from human tumours. Br Med J 1964;2:490–1.Google Scholar
  25. 26.
    Bech-Hansen NT, Sarangi F, Sutherland DJ, Ling V. Rapid assays for evaluating the drug sensitivity of tumour cells. J Natl Cancer Inst 1977;59:21–7.PubMedGoogle Scholar
  26. 27.
    Wolberg WH. Response of DNA thymine synthesis in human tumor and normal tissue to 5-fluorouracil. Cancer Res 1972;32:130–2.PubMedGoogle Scholar
  27. 28.
    Freshney RI. Some observations on assay of anticancer drugs in culture. In: Dendy PP, ed. Human tumours in short-term culture. New York: Academic Press, 1976:150–5.Google Scholar
  28. 29.
    Costachel O, Fadei L, Badea E. Tumor Cell Suspension Culture on Non Adhesive Substratum. Z Krebsforsch 1969;72:24–31.CrossRefPubMedGoogle Scholar
  29. 30.
    Hamburger A, Salmon SE. Primary Bioassay of Human Myeloma Stem Cells. J Clin Invest 1977;60:846–54.PubMedGoogle Scholar
  30. 31.
    Hamburger AW, Salmon SE. Primary Bioassay of Human Tumor Stem Cells. Science 1977;197:461–3.PubMedGoogle Scholar
  31. 32.
    Alberts DS, Chen HSG, Salmon SE.In Vitro Drug Assay: Pharmacologic Considerations. In: Salmon SE, ed. Cloning of Human Tumor Stem Cells. New York: Alan R Liss Inc., 1980:197–208.Google Scholar
  32. 33.
    Frei E, Lazarus H. Predictive tests for cancer chemotherapy. N Engl J Med 1978;298:1358–9.PubMedGoogle Scholar
  33. 34.
    Rupniak T, Hill BT. The poor cloning ability in agar of human cells from biopsies of primary tumors. Cell Biol Int Rep 1980;4:479–86.CrossRefPubMedGoogle Scholar
  34. 35.
    Steel G. Human tumor kinetics,in vitro sensitivity. ULCC Conference on clinical oncology. Bern: Swiss Cancer League, 1981.Google Scholar
  35. 36.
    Selby PJ, Buick RN, Tannock I. A critical appraisal of the ‘human tumor stem-cell assay’. N Engl J Med 1984;308:129–34.Google Scholar
  36. 37.
    Von Hoff DD. Editorial: ‘Send this patient's tumor for culture and sensitivity’. N Engl J Med 1983;308:154–5.PubMedGoogle Scholar
  37. 38.
    Rasey JS, Nelson NJ. Response of anin vivo-in vitro tumour to X-rays and cytotoxic drugs: effect of tumour disaggregation method on cell survival. Br J Cancer 1980;41(suppl IV):217–21.Google Scholar
  38. 39.
    MacKintosh FR, Evans TL, Sikic BI. Methodologic problems in clonogenic assay of spontaneous tumors. Cancer Chemother Pharmacol 1981;6:205–10.CrossRefPubMedGoogle Scholar
  39. 40.
    Tveit KM, Endresen L, Rugstad HE, Fodstad O, Pihl A. Comparison of two soft-agar methods for assaying chemosensitivity of human tumoursin vitro: malignant melanomas. Br J Cancer 1981;44:539–44.PubMedGoogle Scholar
  40. 41.
    Agrez MV, Kovach JS, Lieber MM. Cell Aggregates in the soft agar ‘human tumour stem-cell assay’. Br J Cancer 1982;46:880–8.PubMedGoogle Scholar
  41. 42.
    Bertoncello I, Bradley TR, Campbell JJ, et al. Limitations of the clonal agar assay for the assessment of primary human ovarian tumour biopsies. Br J Cancer 1982;45:803–11.PubMedGoogle Scholar
  42. 43.
    Salmon SE, Von Hoff DD.In Vitro Evaluation of Anticancer Drugs with the Human Tumor Stem Cell Assay. Semin Oncol 1981;8:377–85.PubMedGoogle Scholar
  43. 44.
    Courtenay VD, Mills J. Anin vitro colony assay for human tumours grown in immune-suppressed mice and treatedin vivo with cytotoxic agents. Br J Cancer 1978;37:261–8.PubMedGoogle Scholar
  44. 45.
    Courtenay VD, Selby PJ, Smith IE, Mills J, Peckham MJ. Growth of human tumour cell colonies from biopsies using two soft-agar techniques. Br J Cancer 1978;38:77–81.PubMedGoogle Scholar
  45. 46.
    Bateman AE, Peckham MJ, Steel GG. Assays of drug sensitivity for cells from human tumours:in vitro andin vivo tests on a xenografted tumour. Br J Cancer 1979;40:81–8.PubMedGoogle Scholar
  46. 47.
    Bateman AE, Selby PJ, Steel GG, Towse GDW.In vitro chemosensitivity tests on xenografted human melanomas. Br J Cancer 1980;41:189–98.PubMedGoogle Scholar
  47. 48.
    Tveit KM, Fodstad O, Olsnes S, Pihl A.In vitro sensitivity of human melanoma xenografts to cytotoxic drugs. Correlation within vivo chemosensitivity. Int J Cancer 1980;26:717–22.PubMedGoogle Scholar
  48. 49.
    Tveit KM, Fodstad O, Lotsberg J, Vaage S, Pihl A. Colony growth and chemosensitivityin vitro of human melanoma biopsies. Relationship to clinical parameters. Int J Cancer 1982;29:533–8.PubMedGoogle Scholar
  49. 50.
    Von Hoff DD, Hoang M. A new perfused capillary cloning system to improve cloning of human tumors. Proceedings ASCO 1982;abstract 1225:310.Google Scholar
  50. 51.
    Rupniak HT, Dennis LY, Hill BT. An intercomparison ofin vitro assays for assessing cytotoxicity after a 24 hour exposure to anti-cancer drugs. Tumori 1983;69:37–42.PubMedGoogle Scholar
  51. 52.
    Tanigawa N, Kern DH, Hikasa Y, Morton DL. Rapid Assay for Evaluating the Chemosensitivity of Human Tumors Soft Agar Culture. Cancer Res 1982;42:2159–64.PubMedGoogle Scholar
  52. 53.
    Bradley ED, Reichert CM, Brennan MF, Von Hoff DD. Direct cloning of human parathyroid hyperplasia cells in soft-agar culture. Cancer Res 1980;40:3694–6.PubMedGoogle Scholar
  53. 54.
    Stephens TC, Currie GA, Peacock JH. Repopulation of γ-irradiated Lewis lung carcinoma by malignant cells and host macrophage progenitors. Br J Cancer 1978;38:573–82.PubMedGoogle Scholar
  54. 55.
    Alberts DS, Chen HSG. Tabular summary of pharmacokinetic parameters relevant toin vitro drug assay. In: Salmon SE, ed. Cloning of Human Tumor Stem Cells. New York: Alan R Liss Inc., 1980:351.Google Scholar
  55. 56.
    Slee PHThJ, De Bruijn EA, Driessen OMJ, Hermans J, Van Oosterom AT. Pharmacokinetics of the Cytostatic Drugs Used in the CMF-Regimen. Anticancer Res 1983;3:269–72.PubMedGoogle Scholar
  56. 57.
    Donelli MG, D'Incalci M, Garattini S. Pharmacokinetic Studies of Anticancer Drugs in Tumor-Bearing Animals. Cancer Treat Rep 1984;68:381–400.PubMedGoogle Scholar
  57. 58.
    Alberts DS, Salmon SE. Pharmacologic studies of anticancer drugs using the human tumour stem cell assay. Third NCI-EORTC symposium on new drugs in cancer chemotherapy. Brussels 1981; Abstract 17.Google Scholar
  58. 59.
    Hamburger AW. Use ofin Vitro Tests in Predictive Cancer Chemotherapy. J Natl Cancer Inst 1981;66:981–8.PubMedGoogle Scholar
  59. 60.
    Holmes H, Little J. Tissue-culture micro test for predicting response of human cancer to chemotherapy. Lancet 1974;2:985–7.CrossRefPubMedGoogle Scholar
  60. 61.
    Slee PHThJ, Van den Berg L, De Bruijn EA, Van Oosterom AT.In vitro dose-effect relationships of anticancer agents [Abstract]. Pharm Weekbl [Sci] 1984;6:179.Google Scholar
  61. 62.
    Carter SK. Predictors of Response and Their Clinical Evaluation. Cancer Chemother Pharmacol 1981;7:1–4.CrossRefPubMedGoogle Scholar
  62. 63.
    Von Hoff DD, Coltman Jr CA, Forseth B. Activity of 9–10 Anthracenedicarboxaldehyde bis[(4,5-dihydrol-H-imidazol-2-yl)hydrazone]dihydrochloride (CL216,942) in a Human Tumor Cloning System — Leads for Phase II Trials in Man. Cancer Chemother Pharmacol 1981;6:141–6.PubMedGoogle Scholar
  63. 64.
    Ahmann FR, Meyskens Jr FL, Moon TE, Durie BGM, Salmon SE.In Vitro Chemosensitivities of Human Tumor Stem Cells to the Phase II Drug 4′-(9-Acridinylamino) methanesulfon-m-anisidide and Prospectivein vivo correlations. Cancer Res 1982;42:4495–8.PubMedGoogle Scholar

Copyright information

© Bohn, Scheltema & Holkema 1985

Authors and Affiliations

  • P. H. Th. J. Slee
    • 1
  • A. T. van Oosterom
    • 1
  • E. A. de Bruijn
    • 1
  1. 1.Department of Clinical OncologyState University of LeidenAA LeidenThe Netherlands

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