Dr. Ascensão. At the Washington DC VAMC in our first cycle it is day 1, 4, 8, and 11 with bortezomib, but after that we go pretty much to weekly bortezomib. We also tend to use what I would call lower dose 20 mg dexamethasone in patients over the age of 70 years. And we feel that it is a lot less toxic. We use subcutaneous bortezomib for pretty much everybody else.
Managing Adverse Effects
Dr. Chauncey. I think we’re all using subcutaneous bortezomib at this point. Dexamethasone doesn’t get a lot of independent attention, but there’s no question that, as Dr. Mehta mentioned, the older regimen that we used, the dose-dense dexamethasone of the VAD regimen, was
quite disabling. In addition to obvious hyperglycemia, there were psychiatric problems and, ultimately, profound steroid myopathy that seemed to affect patients in variable fashion. Different patients seem to be more or less susceptible, but after a couple of cycles, it starts to kick in and is progressive.
So we’ve since abandoned those massive doses. But when you look at the ECOG study (E4A03) that really defined the lower dose (40 mg weekly), there’s no question the higher dose was more toxic but also more effective in terms of disease response. While there are many older patients that I would start with a lower dose of dexamethasone, whether it’s with lenalidomide or bortezomib, I keep in mind there can be a steep dose response curve for dexamethasone. If you’re giving 20 mg and you’re not getting the response you need, then you increase the dose. There is definitely a dose response, but the higher doses are just not as well tolerated.
Dr. Cosgriff. I don’t know if other institutions are doing it, but instead of doing 40 mg as a single dose because of patient performance status, providers in Portland will prescribe 20 mg on days 1, 2, 8, 9, 15, and 16. They’ll break up that 40 mg dose and give it that way.
Dr. Chauncey. I don’t know if that strategy is biologically equivalent in terms of antimyeloma activity or less toxic in terms of myopathy. There’s almost always some disease marker to track, so that whether you’re using the serum free-light chain assay or serum protein electrophoresis, you can see if the strategy you’re using is working in real time.
Dr. Cosgriff. I’ve never known whether it’s been shown to be more efficacious or if it’s just a way of getting around some of the adverse effects. However, it does pose some alternate challenges. With higher doses of steroids, you’re looking at 2 days where the patient can become hyperglycemic, if not, a little bit longer.
The other thing with it is that adding on that extra day of dexamethasone can interfere with some other drugs and some other therapies. In individuals who have had a deep vein thrombosis for whatever reason and they’re on warfarin, now we have an agent that really screws up our warfarin monitoring. We would have to consider switching them to another agent.