Proposal for the Application of Xenografts in Screening for New Anticancer Agents and in Selecting Tumor Types for Phase II Clinical Trials

  • B. Winograd
  • M. W. Lobbezoo
  • H. M. Pinedo
Part of the ESO Monographs book series (ESO MONOGRAPHS)


The selection of drugs for clinical evaluation in can cer chemotherapy is usually based on the activity in several antitumor test systems. If a drug has a promising activity profile, can be produced in a reliable dosage form and does not show prohibitive toxicity in animals, it is a candidate for clinical evaluation. This is different from most other areas of drug development where a clinical candidate must perform well also in preclinical toxicology studies, thus having a large therapeutic index. In the past decades antitumor testing has mainly been performed in murine tumors in vivo and in vitro. A systematic screen to discover and characterize new lead compounds has been applied by the American National Cancer Institute (NCI) (1). Other institutes performing preclinical antitumor testing used the same or similar models and methods as the NCI. Although the NCI screening system was revised several times, the primary selection of new lead compounds depended heavily on the use of the murine leukemia models L1210 and P388, as the primary screen (2, 3). In 1975 several murine solid tumors and 3 human tumor xenografts (tumor lines) in nude mice were included in the tumor panel, i.e., secondary screen. These tumor models were expected to select drugs active in human solid tumors and predict clinical activity in the major human solid tumors, i.e., lung, breast and colorectal cancer (4, 5, 6).


Nude Mouse Tumor Line Human Tumor Xenograft Preclinical Phase Secondary Screen 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Venditti JM: Preclinical drug development: rationale and methods. Sem in Oncol 1981 (8): 349–361Google Scholar
  2. 2.
    Venditti JM, Wesley RA and Plowman J: Current NCI pre clinical antitumor screening in vivo: results of tumor panel screening 1976–1982 and future directions. In: Garattini S, Goldin A, Hawkins S (eds) Advances in Pharmacology and Chemotherapy. Academic Press, Orlando 1984 (20): 1–20Google Scholar
  3. 3.
    Goldin A, Venditti JM, MacDonald JS, Muggia FM, Henney JE and DeVita Jr VT: Current results of the screening program at the Division of Cancer Treatment, National Cancer Institute. Eur J Cancer 1981 (17): 129–142PubMedCrossRefGoogle Scholar
  4. 4.
    Corbett TH, Griswold jr DP, Roberts BJ, Peckham JC and Schabel Jr FM: Evaluation of single agents and combinations of chemotherapeutic agents in mouse colon carcinomas. Cancer 1977 (40): 2660–2680PubMedCrossRefGoogle Scholar
  5. 5.
    Martin DS, Fugmann RA, Stolfi RL and Hayworth PE: Solid tumor animal model therapeutically predictive for human breast cancer. Cancer Chemother Rep Part 2 1975 (5): 89–109Google Scholar
  6. 6.
    Ovejera AA and Houchens DP: Human tumor xenografts in athymic nude mice as a preclinical screen for anticancer agents. Sem in Oncol 1981 (8): 386–393Google Scholar
  7. 7.
    Estey E, Hoth D, Simon R, Marsoni S, Leyland-Jones B and Wittes R: Therapeutic response in phase I trials of antineoplastic agents. Cancer Treat Rep 1986 (70): 1105–1115PubMedGoogle Scholar
  8. 8.
    Marsoni S, Hoth D, Simon R, Leyland-Jones B, De Rosa M and Wittes RE: Clinical drug development: an analysis of phase II trials, 1970–1985. Cancer Treat Rep 1987 (71): 71–80PubMedGoogle Scholar
  9. 9.
    DeVita VT, Oliverio VT, Muggia FM et al: The drug development and clinical trials programs of the Division of Cancer Treatment, National Cancer Institute. Cancer Clin Trials 1979(2): 195–216Google Scholar
  10. 10.
    DCT board approves New Screening Programme, natural product concepts. The Cancer Letter 1985 (11): 4–5Google Scholar
  11. 11.
    Winograd B, Boven E, Lobbezoo MW and Pinedo HM: Human tumour xenografts in the nude mouse and their value as test models in anticancer drug development (re view). In Vivo 1987 (1): 1–14PubMedGoogle Scholar
  12. 12.
    Nowak K, Peckham MJ and Steel GG: Variation in response of xenografts of colo-rectal carcinoma to chemotherapy. Br J Cancer 1978 (37): 576–584PubMedCrossRefGoogle Scholar
  13. 13.
    Shorthouse AJ, Smyth JF, Steel GG, Ellison M, Mills J and Peckham MJ: The human tumor xenograft -a valid model in experimental chemotherapy? Br J Surg 1980 (67): 715–722PubMedCrossRefGoogle Scholar
  14. 14.
    Fujita M, Hayata S and Taguchi T: Relationship of chemotherapy on human cancer xenografts in nude mice to clinical response in donor patients. J Surg Oncol 1981 (15): 211–219CrossRefGoogle Scholar
  15. 15.
    Fiebig HH, Schuchhardt C, Henss H, Fiedler L and Löhr GW: Comparison of tumor response in nude mice and in the patients. Behring Inst Mitt 1984 (74): 343–352PubMedGoogle Scholar
  16. 16.
    Fiebig HH, Neumann HA, Henss H, Koch H, Kaiser D and Arnold H: Development of three human small cell lung cancer models in nude mice. Res Results Cancer Res 1985 (97): 77–86CrossRefGoogle Scholar
  17. 17.
    Osieka R: Studies on drug resistance in a human melanoma xenograft system. Cancer Treat Rev 1984 (11, Suppl A): 85–97Google Scholar
  18. 18.
    Braakhuis BJM, Schoevers EJ, Heinerman ECM, Sneeuwloper G and Snow GB: Chemotherapy of human head and neck cancer xenografts with three clinically active drugs: cis-platinum, bleomycin and methotrexate. Br J Cancer 1983 (48): 711–716PubMedCrossRefGoogle Scholar
  19. 19.
    Bellet RE, Danna V, Mastrangelo MKJ and Berd D: Evaluation of a “nude” mouse-human tumor panel as a predictive secondary screen for cancer chemotherapeutic agents. JNCI 1979 (63): 1185–1188PubMedGoogle Scholar
  20. 20.
    Shorthouse AJ, Jones JM, Steel GG and Peckham MJ: Experimental combination and single-agent chemotherapy in human lung-tumour xenografts. Br J Cancer 1982 (46): 35–44PubMedCrossRefGoogle Scholar
  21. 21.
    Boven E: Conventional agents in human ovarian cancer xenografts. In: Winograd B, Peckham MJ, Pinedo HM (eds) Human Tumour Xenografts in Anticancer Drug Development. ESO Monograph Series. Springer Verlag, Heidelberg 1987: 33–35Google Scholar
  22. 22.
    Bailey MJ, Gazet JC, Smith IE and Steel GG: Chemotherapy of human breast-carcinoma xenografts. Br J Cancer 1980 (42): 530–536PubMedCrossRefGoogle Scholar
  23. 23.
    Giuliani FC, Zirvi KA and Kaplan NO: Therapeutic response of human tumor xenografts in athymic mice to doxorubicin. Cancer Res 1981 (41): 325–335PubMedGoogle Scholar
  24. 24.
    Fodstad Ø, Aass N and Pihl A: Response to chemotherapy of human malignant melanoma xenografts in athymic, nude mice. Int J Cancer 1980 (25): 453–458PubMedCrossRefGoogle Scholar
  25. 25.
    Fiebig HH, Widmer KH, Fiedler L, Wittekind O and Löhr GW: Development and characterization of 51 human tumor models for large bowel, stomach and esophageal cancer. Dig Surg 1984 (1): 225–235CrossRefGoogle Scholar
  26. 26.
    Giuliani FC, Zirvi KA, Kaplan NO and Goldin A: Chemotherapy of human colorectal tumor xenografts in athymic mice with clinically active drugs: 5-fluorouracil and 1-3-bis-(-2-chloroethyl)-1-nitrosourea (BCNU). Comparison with doxorubicin derivatives: 4’-deoxydoxorubicin and 4’-0-methyldoxorubicin. Int J Cancer 1981 (27): 5–13PubMedCrossRefGoogle Scholar
  27. 27.
    Osieka R, Houchens DP, Goldin A and Johnson RK: Chemotherapy of human colon cancer xenografts in athymic nude mice. Cancer 1977 (40): 2640–2650PubMedCrossRefGoogle Scholar
  28. 28.
    Houghton PJ and Houghton JA: Evaluation of single agent therapy in human colorectal tumour xenografts. Br J Cancer 1978 (37): 833–840PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 1988

Authors and Affiliations

  • B. Winograd
    • 1
  • M. W. Lobbezoo
    • 1
  • H. M. Pinedo
    • 1
  1. 1.EORTC New Drug Development OfficeFree University HospitalAmsterdamThe Netherlands

Personalised recommendations