NILOTINIB

[CHALAPATIRAO]

I Plan to start Nilotinib next week. I am from India and like to know how safe is it.

currently any body is using in this group ?

If yes what dose at what intervals ? please update with any improvements and feed back on the side effects if any.

[MBAnderson]

You plan to take Nilotinib next week, but are asking how safe it is, what dose and what the interval of the dosing should be tells me that you absolutely, positively are not ready.

I've posted a lot of blather on this forum, but make it a point of never recommending people take or not take drugs, but in this case I'll make an exception. I take Nilotinib and I strongly recommend against it. Nilotinib IS a dangerous drug. If you're not extremely careful, you will kill yourself.

I've been in communication with 2 other people who were taking it. One was taken 150 mg a day for 18 months and the other was taking 200 mg day for 14 months. Both recently quit saying they could not determine there was any benefit. I've been taken 95 mg twice a day for 10 months (although I titrated up from much lower dose beginning 5 months earlier) and cannot say I see any benefit. I am progressing slowly, but I take a lot of supplements and compounds, so there's no way to know. We believe Pagan and Moussa exaggerated the results.

If you do research, you'll find there's alternative ways to up regulate autophagy.

If your are firmly committed to taking it, read everything that has been published about it before you start and then read it's all again. Nilotinib prolongs the QT interval in some people. That's the interval between heartbeats which is measured in milliseconds. Average is around 400 ms and 500 ms is heartattack zone, i.e., you have less than 1/10 of a second margin. 1 of the Georgetown 12 patients died of a heart attack. My QTc interval went to 464 ms which I learned only because I had frequent EKGs - 15 in the 1st year. I was 1/30 of a second away from killing myself.

The following paragraph does not give enough explicit, precise instructions about the frequency of EKGs, but otherwise, makes the point.

"While approved, nilotinib carries two black box warnings for heart arrhythmia. Electrocardiograms are recommended to monitor the QT interval at baseline, seven days after initiation of nilotinib treatment and periodically thereafter. Additional monitoring is recommended following any dose adjustments. Because of the cardiac issues with nilotinib, pharmacokinetic drug-drug interactions that result in increased nilotinib concentration are of concern. There were five sudden deaths reported in patients receiving nilotinib in an on-going study (n=867; 0.6%). A similar incidence was reported in the expanded access program (20). The relative early occurrence of some of these deaths relative to the initiation of nilotinib suggests the possibility that ventricular repolarization abnormalities may have contributed to their occurrence. Thrombocytopenia, neutropenia and anemia, additional to the underlying leukemia, can usually be treated by decreasing dose or treatment interruption. Elevated hepatic enzymes (grade 3 or 4) are seen in approximately 10–15% of patients but rarely progress to hepatitis (20)."

ncbi.nlm.nih.gov/pmc/articl...

You must have an EKG on the 7th day after changing dose. Also, liver function must be closely monitored.

The Georgetown patients took either 150 mg once a day or 300 mg once a day, but there is little basis for choosing that the dose. If you can get an EKG whenever you want, consider starting at 50 mg a day. I did.

You cannot take this drug with any other drug OR FOOD which is extensively metabolized by the CYP3A4 enzyme or a substrate, otherwise N will not be cleared from your body in sufficient amounts and will accumulate to lethal levels. You must do a contraindications search for every single thing you ingest. Being as you are in India, for example, you might not expect it, but you cannot also take curcumin because it too might prolong the QT interval.

In conclusion, please don't enter into this decision casually.

[park_bear in reply to MBAnderson]

Well done, MBA!

>We believe Pagan and Moussa exaggerated the results.

Yes, and minimized the downside. Something like 40% of patients taking nilotinib experience skin reactions yet none were reported in their trial. It is also apparent that the MJFF was skeptical of their results as well and there was a falling out over jointly running a phase 2 trial. MJFF caught bad press over this. They were caught between a rock and a hard place because to defend themselves they would have had to go public with their concerns over Moussa's work.

[parkie13 in reply to MBAnderson]

Thank you for educating Mary

[CHALAPATIRAO in reply to MBAnderson]

Thanks a lot for educating me about the pitfalls

[JMDean]

I wanted to chime in with MB Anderson. This is a chemotherapy drug with all of the concomitant side effects and toxicity . I would be very cautious about undertaking as protocol on your own. There's a phase 2 study underway right now in the states. I think it would be prudent to wait to see what those results show. As others have alluded to, that initial study was problematic and even reported on findings that didn't use any standardized assessments to document what they were seeing. That kind of anecdotal report is particularly troubling because the study was open label (and funded by one of the participants :-/). This next study is more properly designed and I would wait to see if it replicates the findings from the previous study before subjecting my body to a toxic and potentially lethal drug

If you want to take action right now to impact the progression of your disease, start working with a physiotherapist on an exercise program that you can do as much as you can tolerate (the minimum recommendations is five days a week, 30 minutes a day). Not only Will this impact the disease long-term, you will realize more immediate benefits in quality of life and health, extending all the way to sleep quality and emotional state and even perhaps cognition.