Before any human studies in gerontology are done, I’d suggest very careful evaluation of the risk and etiology of the primary pulmonary hypertension (PPH) seen in a significant number of patients receiving 140 mg QD dose for cancer. I want more time and all the help I can get running that one to the ground. PPH is a uniformly fatal and very unpleasant way to die that is curable only by lung transplant, should you be lucky enough to get one and to live through the surgery and anti-rejection regimen. The myelodepressive and pleural effusion effects of dasatinib appear dose and time course related, and while of concern, are of less concern at such a low dose and (presumably) short duration of Tx.
However, PPH is strange animal – a very strange animal. It is associated with a number of medications, as well as the chronic intermittent hypoxia of sleep apnea. Most cases are idiopathic, meaning the etiology is not known. The concern here is that it may result from alterations in receptor morphology, biochemistry, or from changes to the biochemistry of the pulmonary vascular endothelium, or even to central regulatory mechanisms that control lung capillary tone. As such, in cases of drug induced PPH, this adverse effect can sometimes occur over a wide range of doses. Thus, the incidence of PPH may not be a function of dose above a relatively small amount, and the same may be true of duration of Tx. I also suspect this only happens in humans.
What we really need is the Phase 1 and Phase 2 clinical trials data wherein they were doing dosage escalation studies. These trials are all about safety (especially Phase 1), rather than efficacy. Thus, I suspect the doses used in these initial studies were likely to have been in the range of 50 to 75 mg QD. The incidence of myleotoxicity and of PPH, if any, would thus be very indicative.
If you, or anyone else knows how to get this data, well then you should get it, LOL, and post it here or send to me, or both.
PS, if there is going to be a trial involving 20-30 people, it would be worthwhile to try and get the drug purchased in India and shipped to the U.S. via courier, such as Blue Dot. The current price in India is approximately $55 per 50 mg tablet and $104 per 100 mg tablet, or about $1.00 milligram. This is the OTC pharmacy price where you walk in the door and Kay your money on the counter: no RX is required in India. With those savings, you could afford to fly someone to Mumbai, just to make the purchase! I’ll check with my friends in India and see if any would be willing to make the purchase and do the shipping, presumably for a small “hassle fee”, though this unlikely. The biggest risk is theft en route, which the Indian pharmacies that supply the U.S. get round by paying generous bribes.
PPS, the intrinsic cost of producing this molecule is almost nil. Cipla offered to produce dasatinib for $4.00 per adult dose, however U.S. pressure on the Indian government was successful in preventing this.