RTP On Demand — Head & Neck/Thyroid | Research To PracticeCase: A 52-year-old man with medullary thyroid cancer who experienced disease progression on vandetanib and underwent subsequent treatment with cabozantinib
6:10 minutes.
TRANSCRIPTION:
DR LOVE: So let’s talk about medullary thyroid cancer. And why don’t we begin with one of your cases? DR COHEN: Ah. So we saw a patient, this was a gentleman who was a podiatrist and actually lived in Texas but was well read about his disease and unfortunately was diagnosed with metastatic medullary thyroid cancer. He presented with metastatic disease to both lymph nodes and to bone. DR LOVE: How did he come to present? What happened? DR COHEN: He had bone pain. DR LOVE: Hmm. Wow! DR COHEN: And it was not typical — he was a very active gentleman, in fact, ran long-distance races. And, at first, it was thought to be just a soft-tissue overuse injury. And then eventually somebody did a radiograph and saw that, in fact, there was a lytic lesion and he was eventually was diagnosed with medullary thyroid cancer. He was actually diagnosed from a biopsy of a supraclavicular lymph node, which eventually manifested after the bone pain. DR LOVE: What did he have on physical exam in the thyroid and neck when he presented? DR COHEN: I didn’t see him when he presented, but as far as I know when he presented, he did not have a thyroid mass. In fact, that was only discovered after the biopsy of the supraclavicular lymph node showed medullary thyroid cancer. And so actually it showed neuroendocrine, and then a workup began. And, in fact, they eventually saw a mass in the thyroid gland. DR LOVE: What about his calcitonin levels? DR COHEN: And his calcitonin was very high. I don’t remember what they were at diagnosis, but when we saw him, his calcitonin level was about 10,000. DR LOVE: And so how was he managed initially? DR COHEN: Initially he had actually a thyroidectomy. DR LOVE: How often do you see local control problems in thyroid, differentiated thyroid cancer as well as medullary? DR COHEN: Local control problems are more common in medullary thyroid cancer than it is with differentiated. And that’s because of not only the biology but also the treatments that we have. But I would say overall in differentiated thyroid cancer, probably somewhere in the range of about 20% of patients, and then for medullary, probably a little bit higher than that. About a third of patients will run into local-regional problems. DR LOVE: What kinds of local-regional problems do you see? DR COHEN: Primarily it’s neck nodes. And as you can imagine, the anatomy and impinging on different structures. We can sometimes see vocal cord changes or secondary paralysis of recurrent laryngeal nerve. We can see impingement on the esophagus. DR LOVE: So he gets the surgery. Then what? DR COHEN: He gets the surgery. He gets radiation therapy to the bone lesion. This was a femoral lesion that was causing pain. And then, truly, his treating physicians didn’t really have any options for him. And this is, I think, when he began to really research it himself. He’s in the medical field, and he began to take a look. And he saw that there were clinical trials and things happening with medullary thyroid cancer and then came to our institution. DR LOVE: And what were your thoughts when you saw him? DR COHEN: At that point when we saw him, vandetanib had just been approved. And this was a patient who was clearly a candidate for systemic therapy. He had actually at that point developed new metastatic lesions, new bony lesions and new soft tissue lesions. So clearly, he had progressing disease and was a candidate for systemic therapy. DR LOVE: So what happened? DR COHEN: So this patient initiated therapy with vandetanib. And now remember, he lived in Texas. So we had to warn him about the photosensitivity, because that’s a definite side effect. He did have a little bit of the EGFR-related rash, but that was fairly easy to manage. Eventually, he actually developed QT prolongation, not symptomatic at all, but we saw that on the electrocardiograms that we would get on a regular basis. I think this was about 4 weeks or 6 weeks, he developed QT prolongation. So that actually required a dose reduction. We took him down to 200 mg and he was able to stay on that until, unfortunately, his disease began to progress at about 6 months. DR LOVE: And then what? DR COHEN: At that point, cabozantinib was available to us, fortunately, fortunately for him. And we switched him over to cabozantinib. DR LOVE: What happened then? DR COHEN: He didn’t have a response, but he did well on cabozantinib. His calcitonin came down. He had developed a new supraclavicular lesion and that actually shrunk a little bit. Not enough to define a RECIST response, but it shrunk. And he did fairly well on cabozantinib for about a year. DR LOVE: How did he tolerate it? DR COHEN: He did fairly well. This was a gentleman who could put up with a fair bit of side effects. So I think he definitely had side effects from the drug, but he didn’t complain too much. But he did have the fatigue. He had diarrhea. He ended up being able to stay on the full dose of cabozantinib for about 6 months. And then we eventually did have to dose reduce him, primarily because of abdominal discomfort and diarrhea. DR LOVE: So he’s still on cabozantinib now? DR COHEN: And he remains on cabozantinib. DR LOVE: What would you be thinking if he had progression at this point? DR COHEN: That’s a real problem for these patients, because after the 2 available drugs, we really don’t know what to do for these patients. And as we’re beginning to use these agents more and more in medullary thyroid cancer, we’re beginning to see, unfortunately, patients who have become refractory to both the available drugs. And we really don’t know what to use. There are some data looking at mTOR inhibitors, or the rapalogs, especially in combination with one of these drugs. And sometimes we’ll go to that. Of course we do look for a clinical trial if it’s available. But the reality is that that’s an unanswered question. |