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Unfortunately, the treatment of most common solid tumors in adults has not reproduced the encouraging improvements in response and survival demonstrated with chemotherapeutic intervention in the hematological cancers over the last 2030 years. Many reasons can be cited for this disappointing state of affairs, but it is clear that for the common solid cancers (lung, colorectal, breast), in their advanced stages, chemotherapy is (at best) only palliative. |
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In view of the prevalence, mortality, social, and economic impact of cancer in the developed countries of the world, the importance of drug development in this area of medicine is self-evident. This is reflected in the level of activity and resource that is dedicated to anticancer drug development, both within the pharmaceutical industry and by governmental agencies. In spite of this expenditure of effort and money only a handful of new anticancer drugs have been marketed in the last 10 years. This is particularly true if one excludes derivative compounds, such as carboplatin, or those said to reduce particular toxicities of the parent, e.g., epirubicin. It is even more disappointing to note that, in terms of producing real impact on survival for a common solid tumor, cisplatin is unique (though Taxol may change this) over the last 20 years. |
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This has to be viewed as a failure of the drug development process. In this chapter I will attempt to highlight some of the unique problems of anticancer drug development (as opposed to other drugs). I will also address areas in which my personal view is that changes will be required to remedy this situation. |
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It is also worth stressing that our current armamentarium of drugs could be utilised more efficiently [1], with worthwhile improvements in our ability to palliate or even cure malignancies and I will highlight those areas where early development processes could be modified to optimise the eventual clinical utility of an anticancer drug. |
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A further level of complexity is given to anticancer drug development because of the widespread clinical use of combinations of cytotoxics. This is often not (never ?) addressed in the early development of cytotoxic agents. The complexities of this issue are beyond the scope of this contribution, but considerations of the therapeutic place of a compound have clear and important implications in strategic planning decisions within the pharmaceutical industry. |
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A cytotoxic drug of proven clinical utility may be chemically modified to produce a series of derivatised molecules that are then tested for anticancer activity or toxicity profile relative to the parent compound. This approach may |
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