Update on Treatment of Advanced Liver Cancer - Episode 9
Transcript:Ghassan K. Abou-Alfa, MD: Let’s go back to sorafenib a little bit. I have to say, sometimes boredom can come into the thoughts of an oncologist, and sometimes we hear, ‘Oh, it’s not effective, or it has side effects.’ Richard, tell us the truth. What does sorafenib do? What can it do to benefit the patients? How difficult or how easy is it to handle?
Richard Finn, MD: I think probably this will come up repeatedly because the data from the SHARP study, that initially got the drug approved, has stood the test of time. All these phase III studies have been equivalent or inferior to sorafenib, and we’ve also seen in other studies that there’s more to it than this 3-month survival. There are some groups that are living 14 months or longer. To talk in the practical sense—given I’m from a center where I’ve had a lot of experience with the compound—the drug is manageable. You know, 400 mg twice a day is the FDA-approved dose. Everybody will say that no one can tolerate that. That’s not necessarily true, there are patients who can tolerate it. Do we all start our patients at 400 twice a day the day we see them? No. I think there have been data, as well as clinical experience, that say starting 200 mg twice a day, and then dose titrating quickly within 2 to 3 weeks helps patients stay on therapy, and also teases out the patients who might have a super hypersensitivity, or get bad hand-foot syndrome.
I think the most common toxicities we see are unique across the globe; GI toxicity—whether that’s just anorexia or diarrhea—the dermatologic toxicity, the hand-foot syndrome, and fatigue. Hand-foot-skin syndrome can be managed with education about trying to avoid pressure on the hands and feet, as well as using urea-based creams. There was a phase III study published in JCO (Journal of Clinical Oncology), I think in this past year that was presented at ASCO that showed that prophylactic use of these urea-based creams actually helps patients stay on the drug and decreases the risk of hand-foot-skin reaction. And then, diarrhea; all of us are comfortable in medical oncology managing that in the context of irinotecan, capecitabine, and other chemotherapy agents. And with this drug, it’s not much different. Imodium, and being in contact with the patients, I think is critical. Just because it’s an oral drug doesn’t mean you give it to them and you see them 3 months later; they need to come back. Typically, I’ll see them within 10 to 14 days of starting, and probably every 2 weeks for the first month-and-a-half, 2 months. And then patients can go monthly once they’re on a stable dose and having stable toxicities.
Ghassan K. Abou-Alfa, MD: Fair enough. This is really very important information. Let’s look at the population because, as we just heard, transplant, surgery, local therapy, ultimately, they don’t serve except for a certain number in the population with HCC. And, unfortunately, a lot of those patients ultimately will recur with some metastatic disease and, thus, the very critical need we’re always having is systemic therapy that will be of help for patients with metastatic disease. And, that’s why sorafenib came into play since 2007 and has helped, no doubt, many people. The challenge always comes, and no question, I agree with Richard. Actually, jokingly, we talk about the comparative arm of those studies that came out as SHARP-2, SHARP-3, and SHARP-4 because literally, it just always reproduces that 10.7-month median overall survival amount, or close to it. Yes, there has been a lot of data questioning the dosing and the tolerance, but I would probably agree, 400 mg twice a day would be the appropriate dose to start with and, of course, adjusted as deemed necessary. But don’t give up because it seems that the leeway that you can have in regard to biologic activity and what you can do in that regard is pretty wide, and definitely you have a lot of maneuvering you can apply to the patients.
Important though, as Richard mentioned, this is not a pill that you just hand out to the patient and say, ‘Call me in a month, or I will check you in 2 months.’ This is something that you have to follow very closely. I’ll give you just an example that we use at Sloan Kettering—and other centers are doing the same—some form of telemedicine, if you want to call it that way, where after starting sorafenib, in a few days we might very well call the patient and understand what kind of symptoms they might have. And if there’s any question about any form of hand-foot syndrome, which is a drug-limiting toxicity of the drug, we’ll ask to have some pictures sent to us through our portal—which is a secure system which all hospitals have nowadays. We look at the pictures and decide accordingly how to adjust the drug. And you will be amazed how much you can really reduce on the chance of having what we call grade 3—where there’s peeling of the skin which can be very hurtful, very painful—simply by a close follow-up with the patient. So, very, very important to have that close follow-up, as Richard said as well.
Transcript Edited for Clarity