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become even more complex as we reach further back into control of DNA translation and posttranslational mechanisms of protein synthesis regulation. |
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One unifying principle may be attainable. We should strive whenever possible to design trials that look at the relevant actions of drugs and attempt to measure such actions (or some surrogate of action) as accurately as possible in those individuals who volunteer for early clinical trials of potential novel antitumor agents. Thus if we are testing a Topoisomerase inhibitor, would it not be possible to measure inhibition of the enzyme in the tumor or some surrogate tissue, and to define activity in terms of enzyme inhibition rather than the incidence of life-threatening toxicities? |
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The future of cancer treatment is inextricably linked with the drug development process. We must find ways of getting the best out of the massive efforts in this area. |
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3. K. D. Paull, R. H. Shoemaker, L. Hodes, et al. Display and analysis of patterns of differential activity of drugs against human tumour cell lines: Development of mean graph and COMPARE algorithm. J. Natl. Cancer Inst. 81: 10881092, 1989. |
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5. R. Sykes. Innovations on the Pharmaceutical Industry. BMJ 309: 422423, 1994. |
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7. EORTC New Drug Development Committee: EORTC guidelines for phase I trials with single agents in adults. European Journal of Cancer and Clinical Oncology 21: 10051007, 1985. |
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8. J. M. Collins, C. K. Grieshaber, and B. A. Chabner. Pharmacologically guided phase I clinical trials based upon preclinical drug development. J. Natl. Cancer Inst. 82: 1321, 1990. |
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9. A. L. Jackman, G. A. Taylor, A. H. Calvert, et al. Modulation of antimetabolite effects. Effects of thymidine on the efficacy of the quinazoline-based thymidylate synthetase inhibitor CB3717. Biochem. Pharmacol. 33: 3269, 1984. |
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10. J. Cassidy, C. Lewis, A. Setanoians, L. Adams, D. J. Kerr, A. H. Calvert, G. W. Brown, A. J. Pateman, E. M. Rankin, and S. B. Kaye. Phase I trial of GR 63718A. Br. J. Cancer 60: 457, 1989. |
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11. J. S. Penta, G. L. Rosner, and D. L. Trump. Choice of starting dose and escalation for phase I studies of antitumour agents. Cancer Chemother. Pharmacol. 31: 247250, 1992. |
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