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Appropriate Use of Chemotherapy in HNSCC

Panelists: Ezra Cohen, MD, UC San Diego Moores Cancer Center; Viktor Grünwald, MD, Medical School Hannover; Kevin Harrington, MD, PhD, The Royal Marsden NHS Foundation; Tanguy Y. Seiwert, MD, The University of Chicago Medical Center
Published: Wednesday, Dec 28, 2016


Transcript:

Ezra Cohen, MD:
Let’s now turn the discussion to talking about the use of systemic therapy in patients with locally-advanced disease up front. Kevin, what are some of the triggers to add chemotherapy to radiation?

Kevin Harrington, MD, PhD: Well, the guidance is very clear in this regard. It should be patients with stage III or IV disease. It should not be used in earlier-stage disease. We would consider patients who are younger than 70 years of age to be eligible for this treatment. We know, as I’ve already mentioned, that the meta-analysis doesn’t support the use of concomitant chemotherapy in older age groups. And although that may be controversial and there may be some who maintain that you can define biological age even in an older age group, I would contest that view. And so, we would tend to use cisplatin as a monotherapy. The practice in Europe, and Viktor may have some comments on this, includes, perhaps, carboplatin and 5-FU. And in the NCCN guidelines, that’s also included as one of the options in this regard.

We would use cisplatin conventionally at a dose of 100 mg/m2 every 3 weeks. And, again, that’s in line with guidance. There is a tendency in many of the centers and, indeed, some of the lower-volume centers—maybe some of the less experienced centers or more community-based centers within the UK and elsewhere—to use a regimen that’s perceived as being a little gentler, which is 40 mg/m2 every week. I think, in fact, that’s not correct. I think the data support the fact that that is just as toxic as thrice-weekly chemotherapy. It isn’t, in fact, kinder to patients. And I think there is now a real concern that it’s less efficacious as well. So, the gold standard is clearly 100 mg/m2 of cisplatin delivered every 3 weeks during a standard course of radiotherapy.

Ezra Cohen, MD: And for advanced-stage patients primarily, Viktor, let me turn to you. You talked about the postoperative setting earlier. When do you use chemotherapy in the postoperative setting?

Viktor Grünwald, MD: So, I actually would like to comment on what Kevin said.

Ezra Cohen, MD: Please.

Viktor Grünwald, MD: Because I think the 100-mg/m2 doses are really controversial, aren’t they? Because, it’s for guidance. It’s what you should do. This is where we have clear evidence for. The question will be, if you’re not doing the full, you consider the patient not able to go through the whole course of full-dose cisplatin. What do you with these patients? What would be your alternative approach? You go down to weekly dosing? You switch to cetuximab? How do you manage this? Because I think these are the concerns that the doctors have that go for weekly dosing, aren’t they?

Kevin Harrington, MD, PhD: They are indeed. And, in fact, we very infrequently use cetuximab as an alternative. We would tend to use, actually quite often, carboplatin instead of cisplatin. And, indeed, we conducted a matched-pair analysis to show that there was no significant detriment to patients. I know that doesn’t carry the same weight as a meta-analysis or a randomized trial, but it gave us the reassurance that giving carboplatin instead of cisplatin was a reasonable approach in this group of patients.

Ezra Cohen, MD: And Viktor, so we don’t leave that postoperative question hanging, what are the parameters they use post operatively to add chemotherapy?

Viktor Grünwald, MD: For adding chemotherapy? So, basically, this is when it comes down to a lymph node invasion and if it’s, as Kevin said, stage III and IV and if you have spread within the lymph node beyond the capsular, for instance, that would be a trigger for us to radiate on chemotherapy. When we consider radiotherapy, it is not perceived as enough to deliver to that patient as postoperative treatment.

Kevin Harrington, MD, PhD: There’s also the other cost consideration at the primary tumor site as well. And there is, of course, some controversy around that as to whether or not it is the so-called R2 resection with less than a 1 mm margin or the R1 resection 1 mm to 5 mm. And I think the unified guidelines are clear on this: that they are tumors where there is an involved margin of less than 1 mm. The addition of platinum-based postoperative chemoradiation yields a benefit in terms of locoregional control and survival, in the European study, at least.

Ezra Cohen, MD: Yes. I think most of us would approach it exactly as you said.

Transcript Edited for Clarity
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Transcript:

Ezra Cohen, MD:
Let’s now turn the discussion to talking about the use of systemic therapy in patients with locally-advanced disease up front. Kevin, what are some of the triggers to add chemotherapy to radiation?

Kevin Harrington, MD, PhD: Well, the guidance is very clear in this regard. It should be patients with stage III or IV disease. It should not be used in earlier-stage disease. We would consider patients who are younger than 70 years of age to be eligible for this treatment. We know, as I’ve already mentioned, that the meta-analysis doesn’t support the use of concomitant chemotherapy in older age groups. And although that may be controversial and there may be some who maintain that you can define biological age even in an older age group, I would contest that view. And so, we would tend to use cisplatin as a monotherapy. The practice in Europe, and Viktor may have some comments on this, includes, perhaps, carboplatin and 5-FU. And in the NCCN guidelines, that’s also included as one of the options in this regard.

We would use cisplatin conventionally at a dose of 100 mg/m2 every 3 weeks. And, again, that’s in line with guidance. There is a tendency in many of the centers and, indeed, some of the lower-volume centers—maybe some of the less experienced centers or more community-based centers within the UK and elsewhere—to use a regimen that’s perceived as being a little gentler, which is 40 mg/m2 every week. I think, in fact, that’s not correct. I think the data support the fact that that is just as toxic as thrice-weekly chemotherapy. It isn’t, in fact, kinder to patients. And I think there is now a real concern that it’s less efficacious as well. So, the gold standard is clearly 100 mg/m2 of cisplatin delivered every 3 weeks during a standard course of radiotherapy.

Ezra Cohen, MD: And for advanced-stage patients primarily, Viktor, let me turn to you. You talked about the postoperative setting earlier. When do you use chemotherapy in the postoperative setting?

Viktor Grünwald, MD: So, I actually would like to comment on what Kevin said.

Ezra Cohen, MD: Please.

Viktor Grünwald, MD: Because I think the 100-mg/m2 doses are really controversial, aren’t they? Because, it’s for guidance. It’s what you should do. This is where we have clear evidence for. The question will be, if you’re not doing the full, you consider the patient not able to go through the whole course of full-dose cisplatin. What do you with these patients? What would be your alternative approach? You go down to weekly dosing? You switch to cetuximab? How do you manage this? Because I think these are the concerns that the doctors have that go for weekly dosing, aren’t they?

Kevin Harrington, MD, PhD: They are indeed. And, in fact, we very infrequently use cetuximab as an alternative. We would tend to use, actually quite often, carboplatin instead of cisplatin. And, indeed, we conducted a matched-pair analysis to show that there was no significant detriment to patients. I know that doesn’t carry the same weight as a meta-analysis or a randomized trial, but it gave us the reassurance that giving carboplatin instead of cisplatin was a reasonable approach in this group of patients.

Ezra Cohen, MD: And Viktor, so we don’t leave that postoperative question hanging, what are the parameters they use post operatively to add chemotherapy?

Viktor Grünwald, MD: For adding chemotherapy? So, basically, this is when it comes down to a lymph node invasion and if it’s, as Kevin said, stage III and IV and if you have spread within the lymph node beyond the capsular, for instance, that would be a trigger for us to radiate on chemotherapy. When we consider radiotherapy, it is not perceived as enough to deliver to that patient as postoperative treatment.

Kevin Harrington, MD, PhD: There’s also the other cost consideration at the primary tumor site as well. And there is, of course, some controversy around that as to whether or not it is the so-called R2 resection with less than a 1 mm margin or the R1 resection 1 mm to 5 mm. And I think the unified guidelines are clear on this: that they are tumors where there is an involved margin of less than 1 mm. The addition of platinum-based postoperative chemoradiation yields a benefit in terms of locoregional control and survival, in the European study, at least.

Ezra Cohen, MD: Yes. I think most of us would approach it exactly as you said.

Transcript Edited for Clarity
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