Journal of the National Cancer Institute Advance Access originally published online on March 11, 2008
JNCI Journal of the National Cancer Institute 2008 100(6):445-446; doi:10.1093/jnci/djn021
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© The Author 2008. Published by Oxford University Press.
CORRESPONDENCE |
Re: Design of Phase II Cancer Trials Using a Continuous Endpoint of Change in Tumor Size: Application to a Study of Sorafenib and Erlotinib in Non–Small Cell Lung Cancer
Affiliation of author: Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX
Correspondence to: David J. Stewart, MD, FRCPC, Professor of Medicine, Department of Thoracic/Head and Neck Medical Oncology, University of Texas M. D. Anderson Cancer Center, Houston, TX 77030 (e-mail: dstewart{at}mdanderson.org).
In their recent article in the Journal (1), Karrison et al. outline a number of possible advantages of reporting response as a continuous variable (percent change in tumor size) rather than as a dichotomous variable. We agree with them as to the value of reporting response as a continuous variable and would like to suggest some additional possible uses of this approach. We have proposed that plotting percent change in tumor size versus treatment dose might offer increased insight into dose–response relationships and that this might be used to infer predominant resistance mechanisms (2). Furthermore, the relationship of change in tumor size versus dose with the first cycle of therapy may reflect intrinsic resistance mechanisms, whereas the relationship to dose of further change in tumor size with later cycles of therapy may suggest how acquired resistance differs from intrinsic resistance (2). To infer potential major resistance mechanisms, we have used estimated percent tumor cell killing derived from published response rates in assessments of dose–response relationships in non–small cell lung cancer, but we feel that use of percent change in tumor size in individual patients would be preferable if such information were available (3). We have also found that it is feasible to use percent further change in tumor size with each subsequent cycle of therapy to assess the individual impact of each of the four regimens used in a randomized alternating strategy to treat non–small cell lung cancer (4).
REFERENCES
1. Karrison TG, Maitland ML, Stadler WM, Ratain MJ. Design of phase II cancer trials using a continuous endpoint of change in tumor size: application to a study of sorafenib and erlotinib in non small-cell lung cancer. J Natl Cancer Inst (2007) 99(19):1455–1461.
2. Stewart DJ, Raaphorst GP, Yau J, Beaubien AR. Active vs. passive resistance, dose-response relationships, high dose chemotherapy, and resistance modulation: a hypothesis. Invest New Drugs (1996) 14(2):115–130.[Web of Science][Medline]
3. Stewart DJ, Chiritescu G, Dahrouge S, Banerjee S, Tomiak EM. Chemotherapy dose-response relationships in non-small cell lung cancer and implied resistance mechanisms. Cancer Treat Rev (2007) 33(2):101–137.[CrossRef][Web of Science][Medline]
4. Stewart DJ, Tomiak E, Shamji FM, Maziak DE, MacLeod P. Phase II study of alternating chemotherapy regimens for advanced non-small cell lung cancer. Lung Cancer (2004) 44(2):241–249.[CrossRef][Web of Science][Medline]
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J Natl Cancer Inst 2007 99: 1455-1461.
J Natl Cancer Inst 2008 100: 446.
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