RTP On Demand — Head & Neck/Thyroid | Research To PracticeSide-effect profiles of TKIs in thyroid cancer
4:53 minutes.
TRANSCRIPTION:
DR COHEN: I tell patients that there are side effects with these drugs that you’re going to feel and then there are side effects of these drugs that we’re going to monitor. First of all to organize in my mind, and then also to give them a sense that there are side effects that they may not be aware of but that are important. So I start with the ones that they’re going to feel. And for lenvatinib, it’s abdominal pain, diarrhea, fatigue for sure. Some patients do get hand-foot syndrome, although that’s relatively less common with lenvatinib. And then some patients will lose weight. In fact, it’s not a minor issue because patients will notice this and they’ll begin to get worried. And some patients will lose muscle mass and so they’re not able to be as vigorous as before. And so this is something that we really do need to warn patients about. In that respect, I tell them to maintain activity as much as possible. In fact, if they don’t have a regular exercise program, to start an exercise program, within reason, as much as they can tolerate. To really begin to introduce more protein into their diet, so to try to stem that weight loss as much as possible. And to try to eat as much as possible because anorexia is another side effect that they may notice. Of course, we advise them on the diarrhea and how to manage that with antidiarrheals. Everyone has a side effect. So there isn’t a patient I’ve treated that doesn’t come back with some sort of side effect. But I would say about a quarter or a third really do very well with the side effects. Very few complaints. And you don’t have to adjust the dose. Even in the long-term don’t have to adjust the dose. Maybe about a quarter of patients. The rest, we have to either adjust the dose eventually — lower the dose. For some patients, we have to discontinue. But I would say the discontinuations are also uncommon. I would — even though on the clinical trials it was a little bit higher — but, of course, you have to subscribe to a certain set of rules on a clinical trial and take a patient off if they fulfill those rules. I would say it’s less than 10% of patients who I have to discontinue the drug completely because of adverse events. There is one important side effect that I didn’t mention with lenvatinib, and that is hypertension. It is an important side effect to let patients know about and be aware of. In fact, I ask patients to get a blood pressure monitor at home and take their blood pressure. If somebody comes in normotensive, I tell them to call us if the systolic gets above 140 or the diastolic gets above 90, especially if that’s consistent. And then I ask them to come back to the office in 2 weeks, primarily to measure their blood pressure. And every 2 weeks for the first 2 months. Because about two thirds of patients will have an elevation in their blood pressure, and if we don’t get that under control, that can lead to some serious consequences. So that’s something that I do spend some time telling patients about. DR LOVE: And I think that’s a really good point because I think we are getting used to the whole concept, bevacizumab’s out there with hypertension, ramucirumab. But it kind of sounds like with this agent, and maybe the other TKIs in this setting, hypertension is actually more of a problem? DR COHEN: With lenvatinib, as I said, it occurs in about two thirds of patients, maybe even a little bit more than that. DR LOVE: That’s pretty high. DR COHEN: And so the incidence of hypertension is very high, much higher than other TKIs. Probably because it’s such a potent anti-angiogenic with VEGF receptor and FGF receptor inhibition. It’s an issue with the other TKIs but more common with lenvatinib. DR LOVE: And again, thinking about sorafenib in this setting, and the other 2 TKIs, what are your primary concerns other than the VEGF stuff? DR COHEN: Yes. Then the other concern with sorafenib a little bit more than others is the hand-foot. A bit more common with sorafenib. And I tell patients, “Look. This is not a life-threatening toxicity.” Tell us when you’re experiencing it or when you begin to experience it, because that’s the time to try to do something about it.” And then what we try to do is mostly topical therapies. Sometimes patients need mild analgesics. Often, the best way to deal with it or eventual way to deal with it is we need to dose reduce the drug. That’s the main difference in the conversation between lenvatinib and, let’s say, sorafenib. All the other side effects, as well, we discuss. The side-effect profile, if you have a list, is very similar between the TKIs. It’s just the frequencies that change. |