Yes. Novel agent. Starting dose very low - Leo reminded us of that in recent pr - perhaps because he has read some misinformation on the boards about the starting dose being high. It is higher than average for a chemo drug - but still low. Has to be - novel agent - unknown response in humans. Your contention could be true - but they must have pristine protocol in their trials - even if they think it's the safest drug in the world they MUST follow protocol and novel agent protocol is conservative. Also - something I keep forgetting is that novel drug starting dose based on lowest dose that first caused DLT in animals studied - so ctix is actuallt a little hamstrung by the dogs who had the poorest tolerance at lower doses. Here is example but I no longer have link:
If the agent is new to clinical testing, this must be based on animal studies. It has been determined that the dose (defined in mg per meters squared of body surface area) associated with 10% lethality in mice (MELD10) can be predicted to be roughly equivalent to the human MTD 18. This approach is derived from the concept of “allometric scaling” 15, 25. Toxicity as a function of body weight or surface area is assumed to be roughly constant across species. The initial dose for the phase I trial is taken to be 1/10 the MELD10 or, if smaller, 1/3 the LD10 (associated with 10% lethality) in the beagle dog 23. The use of a second species has been shown to be necessary, since in approximately 20% of approximately 90 reviewed drugs, mouse data alone was insufficient to safely predict the human MTD 2. American investigators generally use the dog as the second species, while European investigators generally use the rat, with equivalent safety 2. The next problem is to define dose increments for the subsequent dose levels, and it is here that the various phase I trial designs part company.
