Linked Life Data

11129167

Source:http://linkedlifedata.com/resource/pubmed/id/11129167

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2000-12-20
pubmed:abstractText
There have been extraordinary advances in anticancer therapy over the last few decades, particularly for patients with relatively uncommon malignancies, largely because of the advent of nonspecific cytotoxic chemotherapeutics. Although these agents have also brought improved outcomes for patients with many of the more common solid cancers, it is clear that the point of 'diminishing return' has been reached. The recent development of a plethora of rationally designed target-based anticancer agents has opened up new opportunities and extraordinary therapeutic challenges. Since these agents appear primarily to target malignant cells, they can be expected to be less toxic at clinically effective doses than the cytotoxic agents. Among the various types of rationally designed target-based agents are those that target strategic facets of cell growth signal transduction, angiogenesis, metastasis and cell cycle regulation. While the primary therapeutic benefit of these agents is expected to be decreased tumour growth, evidence suggests that objective tumour responses may also be achieved. However, because of their potentially cytostatic properties, the clinical efficacy of such biologically based agents may not be readily demonstrable with traditional phase I and II study methodologies. Additionally, their dose-toxicity relationships are likely to be less steep than those of the nonspecific cytotoxic agents, thereby rendering such concepts as the maximum tolerated dose less meaningful than alternatives such as the optimal biological dose or the biologically effective dose. Those end-points generally considered, both from a regulatory and clinical viewpoint, to be of secondary importance in trials of cytotoxic agents, such as time to disease progression, disease-related symptoms and quality of life, may evolve into primary end-points. Present findings from preclinical studies suggest that the development, evaluation and general clinical use of rationally designed target-based anticancer agents will require a radical departure from the traditional paradigms if the full potential of these new therapies is to be exploited.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0012-6667
pubmed:author
pubmed:issnType
Print
pubmed:volume
60 Suppl 1
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1-14; discussion 41-2
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
The pursuit of optimal outcomes in cancer therapy in a new age of rationally designed target-based anticancer agents.
pubmed:affiliation
Institute for Drug Development, Cancer Therapy and Research Center, San Antonio, Texas 78229, USA. erowinsk@saci.org
pubmed:publicationType
Journal Article, Review