Expert perspectives on the most common adverse events seen while managing advanced renal cell carcinoma, followed by advice on how best to manage these and counsel patients.
Matthew T. Campbell, MD, MS: I know when we had the meeting earlier, we had discussed a bit about toxicity management with TKIs [tyrosine kinase inhibitors] and the decision on dose reduction vs potentially treatment breaks. How do you counsel patients who are having some toxicity early about staying on treatment and making adjustments so that they maybe are understanding what to anticipate and how they can best maintain quality of life on these therapies?
Brian I. Rini, MD: I tend to tell them that they’re going to need to give us a couple of months to settle into the right dose and maybe even the right schedule of the drug. The line I often use is, “We’re giving everybody the same amount of drug, and there’s just no way that’s going to be the right amount for everybody. It’s impossible.” In fact, it’s probably the wrong amount for most patients. So, education up front that they need to be patient is important, they need to communicate their adverse effects to us. They’re not bothering us, they need to tell us what’s going on because we don’t want them showing up 3 weeks later with such terrible adverse effects that they either need to be admitted or they want to give up on the TKI forever, which I don’t think is the right approach as well.
Then it’s just that iterative process of figuring out their dose and what’s too much. If somebody has significant toxicity really early, then I will dose reduce them. I do think there’s a dose effect of TKIs broadly speaking across kidney cancer and in many patients. So, I do believe in higher doses, but those are going to get you more tumor shrinkage, and that may or may not be important in a particular patient depending on their volume and location of the disease.
I tend to be a dose interrupter more than a dose reducer. I’d rather have patients take higher doses with frequent breaks. I think the pharmacokinetics and dynamics and such of these agents support that. But that takes a lot of effort I think for the average community oncologist in practice. That’s probably a level of effort and expertise that’s unrealistic. I’ve been thinking about TKI dose titration for at least a decade now, and we still don’t know how to give them. That’s the remarkable part, that here we are almost 20 years later, and we’re still talking about what’s the right starting dose and how do we give them. It seems almost unbelievable that we haven’t figured it out by now.
Matthew T. Campbell, MD, MS: Sure. I agree, and it is fascinating how you can get people who are extremely tiny, and you would anticipate they would have struggles, and they do extremely well. And you have a big burly guy for whom a TKI can be extremely hard on them. It is challenging to predict in advance. But I share with you the idea that you have to counsel patients that it’s going to be a trial-and-error period for several months to figure out what exactly is going to be the best dose for them to maximize response to therapy and quality of life.
Brian I. Rini, MD: I will say most of my patients on a long-term TKI, be it monotherapy or combo, will take breaks. I have to tell them that it’s OK to take breaks, that all my patients do, and it’s not going to suddenly cause their disease to go haywire. The first day that they feel like they might need a break from that cumulative fatigue, anorexia, or just being worn down from diarrhea, they should go ahead and take a nice 3- or 4-day break. And schedule those breaks around life events, be they holidays or weddings, or whatever their life events are. It’s hard to measure that quality-of-life improvement, and I don’t think—separate discussion—we do a good job of measuring the quality of life. But just from cumulative years of having patients take breaks, I think it does recharge their batteries, and also gives them some control. If they have an event coming up, I’m going to stop on Thursday, I’ll resume on Monday, and they’ve maybe had a better time of it for that life event. I think that makes a big difference.
Matthew T. Campbell, MD, MS: I agree. I think it definitely helps as well with the patient-physician relationship and with empowering patients to have some control over their cancer treatment.
Transcript edited for clarity.