Posted 04 February 2011 - 03:17 AM
Ponatinib: The Real Deal for Refractory CML?
Dr. Cortes: Yes. They're very interesting results, and as you said, it's the next generation of these tyrosine kinase inhibitors (TKI). Ponatinib is a third-generation TKI, which has the distinct characteristic, as opposed to the other TKIs, of affecting the mutation -- the T315I -- a mutation that is not very common, but we know it's very resistant. None of the drugs that we have now really works in patients who have these mutations. This drug not only can inhibit cells that have this mutation, but it also appears (from preclinical data, anyway) to prevent the emergence of these or any other mutations.
That preclinical work made a very exciting drug for the clinic, so that is what led to this study. This study is a phase 1 study. All of these patients have failed previous therapy with TKIs. Two thirds of these patients have actually failed at least 3 TKIs; these are patients who have gone through one, then another, and then another drug, and they have not responded. The results with ponatinib are very impressive. At least two thirds of patients achieve a major cytogenetic response, and more than half of the patients actually get a complete cytogenetic response. In patients with the T359 mutation, of which only 9 were in chronic phase, all 9 patients responded. These are really unprecedented responses, considering the kind of patients who were included, so it looks like a real drug.
For the benefit of yourself and others please add your CML history into your Signature
02/2010 Gleevec 400mg
2011 Two weakly positives, PCRU, weakly positive
2012 PCRU, PCRU, PCRU, PCRU
2013 PCRU, PCRU, PCRU, weakly positive
2014 PCRU, PCRU, PCRU, PCRU (12/07 began dose reduction w/each continuing PCRU)
2015 300, 250, 200, 150
2016 100, 50/100, 100, 10/17 TFR
2017 01/17 TFR, 04/18 TFR, 07/18 TFR 0.0012, 08/29 TFR 0.001, 10/17 TFR 0.000
2018 01/16 TFR 0.0004 ... next quarterly PCR 04/17
At the earliest opportunity, and whenever possible, lower your TKI dosage; TKIs are toxic drugs and the less we take longterm the better off we are going to be ... this is especially true for older adults.
In hindsight I should have started my dosage reduction two years earlier; it might have helped minimize some of the longterm cumulative toxic effects of TKIs that I am beset with.
longterm side-effects Peripheral Artery Disease - legs (it's a bitch); continuing shoulder problems, right elbow inflammation. GFR and creatinine vastly improved after stopping Gleevec.
Cumulative Gleevec dosage estimated at 830 grams
Taking Gleevec 400mg an hour after my largest meal of the day helped eliminate the nausea that Gleevec is notorious for.
Trey's CML Blog - Stopping - The Odds - Stop Studies - Discussion Forum Cessation Study
Big PhRMA - Medicare Status - Social Security Status - Deficit/Debt