Dose Adjusting Therapy for Patients With Metastatic Renal Cell Carcinoma

A brief review of dose hold or adjustment strategies in the setting of metastatic renal cell carcinoma and when it is appropriate to consider these options.


Chung-Han Lee, MD, PhD: Speaking a little bit more about our patient in the ED [emergency department], the patient was started on a combination of Lenvatinib [Lenvima] plus pembrolizumab [Keytruda]. Lenvatinib was given at the FDA-approved dose of 20 milligrams by mouth on a daily basis and pembrolizumab was started at the 200 milligram by IV every 3 week dose. Certainly, the every 6 week dose is another option for these patients. About 3 weeks since starting treatment, he ends up developing a little bit of hypertension, really a grade 1 so far, and then grade 2 diarrhea. Not uncommon side effects with these types of medications. It’s really one of those things in which even though low-grade diarrhea, or grade 2 diarrhea is considered low grade, but at the same time pretty unpleasant for the patients and probably really debilitating. Then the patient comes into clinic and says, “I have a family reunion in a few weeks” and he just wants to get a better sense of how he wants to handle some of these side effects. Christine, what would you recommend for this patient?

Christine Anderson, NP: We do obviously see this quite a bit. The diarrhea, as you said, can be most impacting on patients and their quality of life and doing things. Certainly, there are times if maybe there is a specific kind of event coming up, sometimes we can hold it for a couple days just to give them a little relief and enjoy their time with family, obviously. We could see how the diarrhea improves even while they’re holding the medication. Then, at that point, if things get better and he’s done with the reunion, we could talk about restarting possibly at a lower dose just to see if he tolerates that a little bit better. Things like that.

Chung-Han Lee, MD, PhD: So whenever we talk about these dose holds or modifications, this is always distressing [to] the patients. I think that sometimes patients try to minimize some of the communication of those side effects because they’re worried that we’re going to snatch the drugs away from them. I think that trying to educate them in advance about these dose modifications are incredibly important. And I think that whenever we talk about these medications that do have potential side effects that they know in advance that dose modifications are common. Lenvatinib is designed with those types of dose modifications in mind. Going from 20 milligrams to 14 milligrams to 10 milligrams, and down to even 8 milligrams is a very common thing that is seen within the regimen. Because when you think about those clinical trial results, those are with dose modifications being mandated. It’s important for them to know that even when we require people to go down, we can still see quite robust efficacy numbers.

Christine Anderson, NP: I think educating them right at the beginning of treatment with the mindset that this is where we’re starting, the highest dose, but we are able to go down and everybody tolerates things differently and just reassure them is important.

Chung-Han Lee, MD, PhD: How long do you normally think before the time of dose modification really is occurring?

Christine Anderson, NP: I think, for the most part, sometimes even the side effects can be quite immediate with these drugs. Within the week of starting, sometimes a diarrhea can start. But I think it’s communicating with them, grading them, and things like that before we dose reduce them.

Chung-Han Lee, MD, PhD: Of course. And then of course, the other thing that we try to do before we dose modify or dose hold is try to maximize the supportive meds that we can offer them. With blood pressure often you want to max out all those potential blood pressure medications. Certainly, we may have to hold the drugs to make sure that we can allow the blood pressure to be controlled and be safe before we resume the drug. For diarrhea, maximizing all of the Imodiums [loperamide] and the Lomotils [diphenoxylate/atropine] before we decide that it’s time to reduce that dose.

Christine Anderson, NP: Yes. Exactly.

Transcript edited for clarity.

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