Pharmaceutisch Weekblad

, Volume 7, Issue 3, pp 93–99 | Cite as

Predictive testing in cancer chemotherapy

I. In vivo
  • P. H. Th. J. Slee
  • A. T. Van Oosterom
  • E. A. De Bruijn
Review Articles


Severalin vivo methods have been assessed for their capacity to predict sensitivity for anticancer agents in humans. Standard strategies have been developed for screening purposes. Adjustments of these strategies are frequently suggested in reports in which the correlation between assay results and clinical therapeutic efficacy is analysed. Low predictivity and high costs of these assays are important reasons for changing the screening strategy.In vivo methods which predict the clinical response in the individual patient, are under investigation. Only the results of the subrenal capsule assay (in normal mice) have been correlated with the clinical response in a larger study. The criticism of the method and the low predictivity for sensitivity in a prospective study provide no reason for optimism. Methods which study changes predicting the clinical response in patients are still in a developmental phase.


Public Health Internal Medicine Large Study Clinical Response Therapeutic Efficacy 
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  1. 1.
    Skipper HE, Schabel FM jr. Tumour Stem Cell Heterogeneity: Implications with Respect to Classification of Cancers by Chemotherapeutic Effect. Cancer Treat Rep 1984;68:43–61.PubMedGoogle Scholar
  2. 2.
    Goodman LS, Wintrobe MM, Dameshek W, et al. Nitrogen mustard therapy: use of methylbis(β-chlorethyl)amino hydrochloride for Hodgkin's disease, lymphosarcoma, and certain allied and miscellaneous disorders. JAMA 1946;132:126–32.Google Scholar
  3. 3.
    Armstrong RD, Diasio RB. Selective activation of 5′-Deoxy-5-fluorouridine by tumour cells as a basis for an improved therapeutic index. Cancer Res 1981;41:4891–4.PubMedGoogle Scholar
  4. 4.
    Driscoll JS. The Preclinical New Drug Research Program of the National Cancer Institute. Cancer Treat Rep 1984;68:63–76.PubMedGoogle Scholar
  5. 5.
    Goldin A, Venditti JM, MacDonald JS, Muggia FM, Henney JE, De Vita VT. Current Results of the Screening Program at the Division of Cancer Treatment, National Cancer Institute. Eur J Cancer 1981;17:129–44.PubMedGoogle Scholar
  6. 6.
    Marsoni S, Wittes R. Clinical Development of Anticancer Agents — A National Cancer Institute Perspective. Cancer Treat Rep 1984;68:77–85.PubMedGoogle Scholar
  7. 7.
    Mulder JH, Van Oosterom AT. Klinisch medicamenteus kankeronderzoek. In: Kanker chemotherapie in de praktijk. Utrecht: Bohn, Scheltema & Holkema, 1981:153–8.Google Scholar
  8. 8.
    Goldin A, Serpick AA, Mantel N. A commentary. Experimental screening procedures and clinical predictability value. Cancer Chemother Rep 1966;50:173–218.PubMedGoogle Scholar
  9. 9.
    Venditti JM. Preclinical Drug Development: Rationale and Methods. Semin Oncol 1981;8:349–61.PubMedGoogle Scholar
  10. 10.
    Staquet MJ, Byar DP, Green SB, Rozencweig M. Clinical Predictivity of Transplantable Tumour Systems in the Selection of New Drugs for Solid Tumours: Rationale for Three-Stage Strategy. Cancer Treat Rep 1983;67:753–65.PubMedGoogle Scholar
  11. 11.
    Venditti JM. The National Cancer Institute Antitumor Drug Discovery Program, Current and Future Perspectives: A Commentary. Cancer Treat Rep 1983;67:767–72.PubMedGoogle Scholar
  12. 12.
    Ovejera AA, Houchens DP. Human Tumour Xenografts in Athymic Nude Mice as a Preclinical Screen for Anticancer Agents. Semin Oncol 1981;8:386–93.PubMedGoogle Scholar
  13. 13.
    Steel GG. The growth and therapeutic response of human tumours in immune deficient mice. Bull Cancer 1978;65:465–72.PubMedGoogle Scholar
  14. 14.
    Steel GG, Courtenay VD, Peckham MJ. The response to chemotherapy of a variety of human tumour xenografts. Br J Cancer 1983;47:1–13.PubMedGoogle Scholar
  15. 15.
    Pantelouris EM. Absence of thymus in a mouse mutant. Nature 1968;217:370–1.PubMedGoogle Scholar
  16. 16.
    Giovanella BC, Stehlin JS jr, Williams LJ jr. Lee SS, Shepard RC. Heterotransplantation of human cancers into nude mice. A model system for human cancer chemotherapy. Cancer 1978;42:2269–81.PubMedGoogle Scholar
  17. 17.
    Giovanella BC, Stehlin JS jr, Shepard RC, Williams LJ jr. Correlation between response to chemotherapy of human tumors in patients and in nude mice. Cancer 1983;52:1146–52.PubMedGoogle Scholar
  18. 18.
    Povlsen CO, Rygaard J. Heterotransplantation of Human Adenocarcinomas of the Colon and Rectum to the Mouse Mutant Nude. A Study of Nine Consecutive Transplantations. Acta Pathol Microbiol Scand 1971;79:159–69.Google Scholar
  19. 19.
    Mitchell DN, Rees RJW, Salisbury AJ. Human myeloma marrow cells in immunologically deficient mice. Br J Cancer 1974;30:33–41.PubMedGoogle Scholar
  20. 20.
    Kameya T, Shimosato Y, Tumuraya M, Oshawa N, Nomura T. Human gastric choriocarcinoma serially transplanted in nude mice. J Natl Cancer Inst 1976;56:325–9.PubMedGoogle Scholar
  21. 21.
    Kopper L, Steel GG. The therapeutic response of three human tumor lines maintained in immune-suppressed mice. Cancer Res 1975;35:2704–13.PubMedGoogle Scholar
  22. 22.
    Povlsen CO, Jacobsen GK. Chemotherapy of a human malignant melanoma transplanted in the nude mouse. Cancer Res 1975;35:2790–6.PubMedGoogle Scholar
  23. 23.
    Bogden AE, Cobb WR, Lepage DJ, et al. Chemotherapy Responsiveness of Human Tumors as First Transplant Generation Xenografts in the Normal Mouse: Six-Day Subrenal Capsule Assay. Cancer 1981; 48:10–20.PubMedGoogle Scholar
  24. 24.
    Griffin TW, Bogden AE, Reich SD, et al. Initial Clinical Trials of the Subrenal Capsule Assay as a Predictor of Tumor Response to Chemotherapy. Cancer 1983;52:2185–92.PubMedGoogle Scholar
  25. 25.
    Edelstein MB, Fiebig HH, Smink T, Van Putten LM, Schuchhardt C. Comparison between Macroscopic and Microscopic Evaluation of Tumour Responsiveness using the Subrenal Capsule Assay. Eur J Cancer 1983;19:995–1009.Google Scholar
  26. 26.
    Smith IE, Courtenay VD, Gordon MY. A Colonyforming Assay for human tumour xenografts using agar diffusion chambers. Br J Cancer 1976;34:476–83.PubMedGoogle Scholar
  27. 27.
    Courtenay VD, Selby PJ, Smith IE, Mills J, Peckham MJ. Growth of human tumour cell colonies from biopsies using the two soft-agar techniques. Br J Cancer 1978;38:77–82.PubMedGoogle Scholar
  28. 28.
    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
  29. 29.
    Kirkwood JM, Marsh JC.In vivo drug sensitivity assay of clonogenic human melanoma cells and correlation with treatment outcome. Cancer Res 1983;43:3434–40.PubMedGoogle Scholar
  30. 30.
    Aardal NP, Talstad I, Laerum DD. Sequential flow cytometric analysis of cellular DNA-content in peripheral blood during treatment for acute leukaemia. Scand J Haematol 1979;22:25–32.PubMedGoogle Scholar
  31. 31.
    Kjaer TB, Thommesen P, Frederiksen P, Bichel P. DNA content in cells aspirated from carcinoma of the prostate treated with oestrogenic compounds. Urol Res 1979;7:249–51.CrossRefPubMedGoogle Scholar
  32. 32.
    Laerum OD, Farsund T. Clinical Application of Flow Cytometry: a Review. Cytometry 1981;2:1–13.PubMedGoogle Scholar
  33. 33.
    Pollack A, Bagwell CB, Block NL, Irvin III GL, Claflin AJ, Stover BJ. Flow Cytometric Analysis of the Response of the R3327-G Rat Prostatic Adenocarcinoma to Endocrine Manipulation. J Surg Oncol 1981;18:389–98.PubMedGoogle Scholar
  34. 34.
    DeVere White R, Deitch AD, Olsson CA. Limitations of DNA Histogram Analysis by Flow Cytometry as a Method of Predicting Chemosensitivity in a Rat Renal Cancer Model. Cancer Res 1983;43:604–10.PubMedGoogle Scholar
  35. 35.
    Blijham GH, Schutte B. Flow cytometry in oncology: a review with emphasis on DNA flow cytometry in human solid tumours. Neth J Med 1983;26:314–20.PubMedGoogle Scholar
  36. 36.
    Vindelov LL, Hansen HH, Gersel A, Hirsch FR, Nissen NI. Treatment of Small-Cell Carcinoma of the Lung Monitored by Sequential Flow Cytometric DNA Analysis. Cancer Res 1982;42:2499–505.PubMedGoogle Scholar
  37. 37.
    Nevinny HB, Hall TC.In situ determination of the antitumour effect of chemotherapeutic compounds. In: Kuemmerle HT, Preziosi P, eds. Proceedings of the Second International Symposium on Chemotherapy, Naples. Basel: S. Karger AG, 1963;111:219–25.Google Scholar
  38. 38.
    Hall TC. Prediction of Responses to Therapy and Mechanisms of Resistance. Semin Oncol 1977;4:193–202.PubMedGoogle Scholar
  39. 39.
    Folca PJ, Glascock RF, Irvine WT. Studies with tritium-labelled hexoestrol in advanced breast cancer. Lancet 1961;2:796.CrossRefPubMedGoogle Scholar
  40. 40.
    Auersperg M, Erjavec M, Us-Krasovec M, Porenta-Vraspir O. Uptake of 99Tc Bleomycin in human squamous cell carcinomas — an indicator of tumour response to chemotherapy. UICC Conference on Clinical Oncology, Lausanne 1981: Abstract 13–0293.Google Scholar
  41. 41.
    Rosen G, Caparros B, Huvos AG, et al. Preoperative Chemotherapy for Osteogenic Sarcoma: Selection of Postoperative Adjuvant Chemotherapy Based on the Response of the Primary Tumor to Preoperative Chemotherapy. Cancer 1982;49:1221–30.PubMedGoogle Scholar
  42. 42.
    Yannopoulos K, Deppe G, Cohen CJ, Gusberg SB. Chemosensitivity testing with Cis-platinum(2)diamminedichloride in squamous cell carcinoma of the cervix uteri. Diagn Gynaecol Obstet 1982;4:115–25.Google Scholar
  43. 43.
    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

Copyright information

© Royal Dutch Association for Advancement of Pharmacy 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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