I just read the definition shown: "About Maximum Tolerated Dose
The highest dose of a biologically active agent given during a chronic study that will not reduce longevity from effects other than carcinogenicity. (from Lewis Dictionary of Toxicology, 1st ed)"
And I feel it enhances my position that something is off-track about this dose concept. After all, when administering in a clinical trial, how can the PI be at all sure that it will NOT reduce longevity? I don't think they can.
I feel this is an old-style way to use drugs based on less regard for Human Subjects. We are much more aware that long-term HARMS are being done with all drugs. We were not when this standard was adopted.
I write as a Cancer Patient Advocate, founder of Annie Appleseed Project.
Dear Ann Fonfa,
In animal studies especially, terms such as LD50- lethal dose at which 50% of test animals will die. Or LC50- lethal concentration etc help us in forming the basis for selecting the doses of particular chemicals/compounds for carrying out various experiments. Yeah, i agree with you this are a bit old-fashioned. Now, a days NOAEL or no observed adverse effect level is gaining popularity.
Regards,
Samrat Das
Hello,
You may find the following abstract to be of interest.
Chevret, S. 2008. Maximum Tolerable Dose (MTD). Wiley Encyclopedia of Clinical Trials. 1–5. http://onlinelibrary.wiley.com/doi/10.1002/9780471462422.eoct627/abstract
Hopefully the reference list to the full article will include some of the earlier studies you are looking for. The abstract also refers to other methods that are alternatives to MTD, which may help support your efforts.
See also.
Takimoto CH. Maximum tolerated dose: clinical endpoint for a bygone era?
Target Oncol. 2009 Apr;4(2):143-7. http://www.ncbi.nlm.nih.gov/pubmed/19377851
Regards
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