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Phase I trials in paediatric oncology — the European perspective

On behalf of the New Agents Group of the United Kingdom Childrens Cancer Study Group

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Abstract

The current recommendations for Phase I trials should allow more confident interpretation of the toxicity and efficacy of new agents by providing a framework for multicentre and international co-operation. An overview of the aims and designs of Phase I trials is presented, along with a summary of current and recently published United Kingdom Childrens Cancer Study Group Phase I trials, and a discussion of some of the difficulties faced in the methodology and evaluation of Phase I studies in children.

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References

  1. Marsoni S, Ungerleider R, Hurson S, Hammershaimb L: Tolerance to antineoplastic agents in children and adults. Cancer Treatment Reports 69:1263–1269, 1985.

    Google Scholar 

  2. Bali F, Holcenberg J, Poplack D: General Principes of Chemotherapy. In: Pizzo P, Poplack D (ed). Principles and Practice of Pediatric Oncology. 2nd edition. Philadelphia: JB Lippincott Company, 1993, pp 197–245.

    Google Scholar 

  3. Smith M, Adamson P, Balis F, et al.: Phase I and pharmacokinetic evaluation of all-trans retinoic acid in pediatric patients. J Clin Oncol 10:1666–1673, 1992.

    Google Scholar 

  4. Lee J, Newman R, Lippman S, et al.: Phase I evaluation of all-trans retinoic acid in adults with solid tumours. J Clin Oncol 11:959–966, 1993.

    Google Scholar 

  5. Boddy AV, Calvete JA, Olson KB, Rafi I: Non-linear pharmacokinetics and metabolism of AG337, a rationally designed thymidylate synthase (TS) inhibitor. Br J Cancer 71(suppl 24):66, 1995.

    Google Scholar 

  6. Newell DR, Pearson A, Balmanno K, et al.: Carboplatin pharmacokinetics in children: the development of a paediatric dosing formula. J Clin Oncol 11:2314–2323, 1993.

    Google Scholar 

  7. Slevin M, Clark P, Joel S, et al.: A randomised trial to evaluate the effect of schedule on the activity of etoposide in small-cell lung cancer. J Clin Oncol 7:1333–1340, 1989.

    Google Scholar 

  8. Houghton P, Cheshire P, Hallman J, Bissery M, Mathieu-Boue A, Houghton J: Therapeutic efficacy of the topoisomerase I inhibitor 7-ethyl-10-(4-[1-piperi-dino])-carbonyloxy-camptothecin against human tumour xenografts: lack of cross-resistance in vivo in tumours with acquired resistance to the topoisomerase I inhibitor 9-dimethylaminomethyl-10-hydroxycamptothecin. Cancer Res 53:2823–2829, 1993.

    Google Scholar 

  9. Arbuck S, Canetta R, Onetto N, Christian M: Current dosage and schedule issues in the development of paclitaxel (TAXOL). Semin Oncol 20(suppl 3):31–39, 1993.

    Google Scholar 

  10. Calvete JA, Balmanno K, Rafi I, Newell DR, Taylor GA, Boddy AV, Lind NB, Bailey NB, Calvert AH, Webber S, Johnston A, Clendennin NJ: Pre-clinical and clinical studies of the novel thymidylate synthase inhibitor AG337, given by oral administration. Br J Cancer 71(suppl 24):70, 1995.

    Google Scholar 

  11. Prendeville J, Crowther D, Thatcher N, Woll PJ, Fox BW, McGown A, Testa N, Stern P, McDermott R, Potter M: A Phase I study of intravenous bryostatin 1 in patients with advanced cancer. British Journal of Cancer 68:418–424, 1993.

    Google Scholar 

  12. Creaven PJ, Pendyla L, Perez R, Meropol NJ, Loewen G, Levine E, Bergholm E, Raghavan D: Phase I study of N1N111 diethylnorspermine, a polyamine analogue, in advanced cancer. Proc Am Assoc Clin Oncol 14:472, 1995.

    Google Scholar 

  13. Pratt CB: The conduct of Phase I–II Clinical Trials in children with cancer. Med Ped Oncol 19:304–309, 1991.

    Google Scholar 

  14. Nitschke R, Sexuer CL, Wunder S: Therapeutic choices made by patients with end-stage cancer. J Pediatrics 101:471–476, 1982.

    Google Scholar 

  15. Furman WL, Pratt CB, Rivera GK: Mortality in pediatric Phase I clinical trials. J Natl Cancer Inst 81:1193–1194, 1989.

    Google Scholar 

  16. CPMP Working Party on the efficacy of Medicinal Products. European Community Commission notes for guidance: Good Clinical Practice for trials of Medicinal Products in the European Community. J Pharmacol Toxicology 67:361–372, 1990.

    Google Scholar 

  17. Lansky SB, List MA, Lansky LL, et al.: The measurement of performance in childhood cancer. Cancer 60:1651–1656, 1987.

    Google Scholar 

  18. Korn EL, Midthune D, Chen TT, et al.: A comparison of two Phase I trial designs. Statistics in Medicine 13:1799–1806, 1994.

    Google Scholar 

  19. Smith MD, Ungerleider R, Reaman G, Seibel N, Bleyer WA, Vietti T, Pratt C, Trueworty R, Pearson ADJ: Considerations on the conduct of Phase I trials in children with refractory cancer. Unpublished draft document from the National Cancer Institute.

  20. Ettinger LJ, Gaynon PS, Kralo MD, et al.: A Phase I study of carboplatin in children with acute leukaemia in bone marrow relapse. A report from the Childrens Cancer Group. Cancer 72:917–922, 1993.

    Google Scholar 

  21. WHO handbook for reporting results of cancer treatment. WHO offset publication 1979. 48-World Health Organisation, Geneva.

  22. Cheson B, Cassieth P, Head D, et al.: Report of the National Cancer Institute — Sponsored Workshop on definitions of diagnosis and response in Acute Myeloid Leukaemia. J Clin Oncol 8:813–819, 1990.

    Google Scholar 

  23. Brodeur GM, et al.: International criteria for diagnosis, staging and response to treatment in patients with neuroblastoma. J Clin Oncol 6:1874–1881, 1988.

    Google Scholar 

  24. Ertmann R, Bode U, Erb N, Forcadell de Bios, Gutjahr P, Haas R, Kuhn N, Siewart H, Landbeck G: Antineoplastic effectiveness and toxicity of idarubicin (4-demethoxy-duanorubicin) in recurrent acute leukaemias in childhood. Klinishie Padiatrie 200:200–204, 1988.

    Google Scholar 

  25. Lashford LS, Lewis IJ, Fielding SL, Flower MA, Meller S, Kernshead JT, Ackery D: Phase I/II study of iodine 131 metaiodobenzylguanidine in chemoresistant neuroblastoma: a United Kingdom Childrens Cancer Study Group investigation. J Clin Oncol 10:1889–1896, 1992.

    Google Scholar 

  26. Negrier S, Micon J, Floret D, Boufett E, Gentet J-C, Philip I, Stamm D, Costil J, Gaspard M, Andreu G, Palmer P, Franks CR, Zucker J-M, Bernard J-L, Fridman WH, Favrot M, Philip T: Interleukin-2 and lymphocyteactivated killer cells in 15 children with advanced metastatic neuroblastoma. J Clin Oncol 9:1363–1369, 1991.

    Google Scholar 

  27. Lemerle J, Lartigau E, Godzinski J, McDowel H, Upward J, Murdoch RD: Efficacy and safety of Granisetron in the prevention of chemotherapy induced emesis in children. Med Ped Oncol 19:420, 1991.

    Google Scholar 

  28. Pearson ADJ, Price L, Hofer C, Lashford L, et al.: Phase I study of continuous intravenous infusion of Low Dose Thiotepa in children. Medical and Paediatric Oncology 23:270, 1994.

    Google Scholar 

  29. Rafi I, Taylor GA, Balmanno K, Calvete JA, Boddy AV, Bailey NB, Lind MJ, Newell DR, Calvert AH, Johnston A, Clendennin N: Phase I study of the novel antifolate AG337 given by a 5 day continuous infusion. Br J Cancer 51(suppl 24):10, 1995.

    Google Scholar 

  30. Marina N, Rodman J, Shema S, et al.: Phase I study of escalating targeted doses of carboplatin combined with ifosfamide and etoposide in children with relapsed tumours. J Clin Oncol 11:554–560, 1993.

    Google Scholar 

  31. Evans WE, Rodman JH, Relling MV, Crom WR, Rivera GK, Pratt CB, Crist WM: Concept of maximum tolerated systemic exposure and its application to Phase I–II studies of anticancer drugs. Med Paed Oncol 19:153–159, 1991.

    Google Scholar 

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Authors and Affiliations

  1. Dept. of Child Health, Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, UK

    E. J. Estlin & A. D. J. Pearson

  2. Dept. of Epidemiology and Public Health, UKCCSG, University of Leicester, 22-28 Princess Road West, LE1 6TP, Leicester, UK

    S. Ablett (UKCCSG Administrator)

  3. Cancer Research Unit, Medical School, University of Newcastle upon Tyne, NE2 4HH, Newcastle upon Tyne, UK

    D. R. Newell

  4. Dept. of Paediatric Oncology, St. James University Hospital, LS9 7TF, Leeds, UK

    I. J. Lewis

  5. Dept. of Paediatric Oncology, Chrisitie Hospital NHS Trust, Wilmslow Rd, M20 9BX, Withington, Manchester, UK

    L. Lashford

Authors
  1. E. J. Estlin
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  2. S. Ablett
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  3. D. R. Newell
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  4. I. J. Lewis
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  5. L. Lashford
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  6. A. D. J. Pearson
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Additional information

Address for offprints: E.J. Estlin, Dept. of Child Health, Sir James Spence Institute of Child Health, Royal Victoria Infirmary, Newcastle upon Tyne, United Kingdom

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Estlin, E.J., Ablett, S., Newell, D.R. et al. Phase I trials in paediatric oncology — the European perspective. Invest New Drugs 14, 23–32 (1996). https://doi.org/10.1007/BF00173679

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