Abstract
Phase I trials in oncology are conducted to obtain information on dose–toxicity relationship. Preclinical studies in animals define a dose with approximately 10% mortality (the murine LD10). One-tenth or two-tenths of the murine equivalent of LD10, expressed in milligrams per meters squared, is usually used as a starting dose in a Phase I trial. It is standard to choose a set of doses according to the modified Fibonacci sequence in which higher escalation steps have decreasing relative increments (100, 65, 50, 40, and 30% thereafter). Toxicity in oncology trials is graded using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (available online from the Cancer Therapy Evaluation Program website http://ctep.cancer.gov).
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Babb, J., Rogatko, A., and Zacks, S. 1998. Cancer Phase I clinical trials: Efficient dose escalation with overdose control. Statistics in Medicine 17:1103–1120.
Barlow, R.E., Bartholomew, D.J., Bremner, J.M., and Brunk, H.D. 1972. Statistical Inference under Order Restrictions. New York: Wiley.
Derman, C. 1957. Nonparametric up and down experimentation. Annals of Mathematical Statistics 28:795–798.
Dixon, W.J., and Mood, A.M. 1954. A method for obtaining and analyzing sensitivity data. Journal of the American Statistical Association 43:109–126.
Durham, S.D., and Flournoy, N. 1994. “Random walks for quantile estimation,” in Statistical Decision Theory and Related Topics V (S.S. Gupta and J.O. Berger, editors), New York: Springer-Verlag, pp. 467–476.
Durham, S.D., and Flournoy, N. 1995. “Up-and-down designs I. Stationary treatment distributions,” in Adaptive Designs (N. Flournoy and W.F. Rosenberger, editors), Hayward, California: Institute of Mathematical Statistics pp. 139–157.
Gezmu, M., and Flournoy, N. 2006. Group up-and-down designs for dose-finding. Journal of Statistical Planning and Inference, in press.
Innocentt et al. 2004
Ivanova, A. 2004. Zoom-in designs for dose-finding in oncology. UNC Technical report 04–03.
Ivanova, A. 2006. Escalation, up-and-down and A + B designs for dose-finding trials. Statistics in Medicine, in press.
Ivanova, A., Montazer-Haghighi, A., Mohanty, S.G., and Durham, S.D. 2003. Improved up-and-down designs for Phase I trials. Statistics in Medicine 22:69–82.
Ivanova, A., and Wang, K. 2004. A nonparametric approach to the design and analysis of two-dimensional dose-finding trials. Statistics in Medicine 23:1861–1870.
Ivanova, A., and Wang, K. 2006. Bivariate isotonic design for dose-finding with ordered groups. Statistics in Medicine, in press.
Korn, E.L., Midthune, D., Chen, T.T., Rubinstein, L.V., Christian, M.C., and Simon, R.M. 1994. A comparison of two Phase I trial designs. Statistics in Medicine 13: 1799–1806.
Lin, Y., and Shih, W.J. 2001. Statistical properties of the traditional algorithm-based designs for Phase I cancer clinical trials. Biostatistics 2:203–215.
O’Quigley, J., Pepe, M., and Fisher L. 1990. Continual reassessment method: A practical design for Phase I clinical trials in cancer. Biometrics 46:33–48.
O’Quigley, J., Shen, J., and Gamst, A. 1999. Two-sample continual reassessment method. Journal of Biompharmaceutical Statistics 9:17–44.
O’Quigley, J., and Paoletti, X. 2003. Continual reassessment method for ordered groups. Biometrics 59:430–440.
Ratain, M.J., Mick, R., Schilsky, R.L., and Siegler, M. 1993. Statistical and ethical issues in the design and conduct of Phase I and II clinical trials of new anticancer agents. Journal of National Cancer Institute 85:1637–1643.
Reiner, E., Paoletti, X., and O’Quigley, J. 1999. Operating characteristics of the standard Phase I clinical trial design. Computational Statistics and Data Analysis 30:303–315.
Robertson, T., Wright, F.T., and Dykstra, RL. 1988. Ordered Restricted Statistical Inference. New York: Wiley.
Rosenberger W.F., and Haines, L.M. 2002. Competing designs for Phase I clinical trials: A review. Statistics in Medicine 21:2757–2770.
Rowinsky, E., Kaufmann, S., Baker, S., Grochow, L., Chen, T., Peereboom, D., Bowling, M., Sartorius, S., Ettinger, D., Forastiere, A., and Donehower, R. 1996. Sequences of topotecan and cisplatin: Phase I, pharmacologic, and in vitro studies to examine sequence. Journal of Clinical Oncology 14:3074–3084.
Storer, B.E. 1989. Design and analysis of Phase I clinical trials. Biometrics 45:925–937.
Stylianou, M., and Flournoy, N. 2002. Dose finding using isotonic regression estimates in an up-and-down biased coin design. Biometrics 58:171–177.
Thall, P., Millikan, R., Mueller, P., and Lee, S. 2003. Dose finding with two agents in Phase I oncology trials. Biometrics 59:487–496.
Tsutakawa, R.K. 1967a. Random walk design in bioassay. Journal of the American Statistical Association 62:842–856.
Tsutakawa, R.K. 1967b. Asymptotic properties of the block up-and-down method in bio-assay. The Annals of Mahtematical Statistics, 38:1822–1828.
von Békésy 1947. A new audiometer. Acta Otolaryngology 35:411–422.
Wetherill, G.B. 1963. Sequential estimation of quantal response curves. Journal of the Royal Statistical Society B 25:1–48.
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2006 Springer
About this chapter
Cite this chapter
Ivanova, A. (2006). Dose-Finding in Oncology—Nonparametric Methods. In: Ting, N. (eds) Dose Finding in Drug Development. Statistics for Biology and Health. Springer, New York, NY. https://doi.org/10.1007/0-387-33706-7_4
Download citation
DOI: https://doi.org/10.1007/0-387-33706-7_4
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-29074-4
Online ISBN: 978-0-387-33706-7
eBook Packages: Mathematics and StatisticsMathematics and Statistics (R0)