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Chemotherapy Procedures for Advanced HNSCC

Insights From: Ezra Cohen, MD, UC San Diego Moores Cancer Center; Robert L. Ferris, MD, PhD, FACS, University of Pittsburgh Cancer Institute; Jared Weiss, MD, University of North Carolina School of Medicine
Published: Wednesday, Jun 01, 2016


Transcript:

Ezra Cohen, MD:
With respect to the use of chemotherapy in squamous cell carcinoma of the head and neck, we really think about it in terms of two major applications. The first is concomitant with radiation and the second is as neoadjuvant or induction chemotherapy. Let’s talk about concomitant chemotherapy first. Here we have a number of options, with probably the most standard option, or certainly the most investigated option, being high-dose cisplatin; so 100 mg/m2 given every 3 weeks. And what we know from that is that it improves survival by about 8%, an absolute improvement of 8% in survival when added to radiation therapy. It’s a modest improvement in survival, but it’s a real improvement in survival.

Along those lines, we also have data with cetuximab when added to radiation therapy alone. And, again, that appears to deliver about the same difference of about 8% to 10% improvement in overall survival at 3 and 5 years when we add cetuximab to radiation. So, from level 1 data, phase III studies, we have two validated options: high-dose cisplatin, 100 mg every 3 weeks, or cetuximab started 1 week prior to radiation and carried through the entire radiation therapy course. But, of course, there are other options that have been studied. In phase II studies, for instance, there’s a lower dose of cisplatin that has been looked at given weekly. That’s often a dose of 40 mg/m2 or sometimes 30 mg/m2, depending on the patient. And from what we can tell, that appears to be effective. It appears to be tolerable. But the reality is that it’s never been tested head-to-head against the 100 mg/m2 regimen in locally advanced head and neck cancer. I would exercise some caution when using the weekly regimen, with the realization that there isn’t level 1 evidence to support that. Other regimens include the use of carboplatin, or carboplatin and paclitaxel given on a weekly basis, cisplatin/5-FU, and some other regimens that are used at different centers. There are different options, with probably the most commonly used options being the cisplatin or the cetuximab.

In terms of induction or neoadjuvant chemotherapy, we do know a few things from phase III studies. We know that TPF—so the combination of docetaxel, platinum, and 5-FU—is superior to platinum/5-FU with respect to overall survival when we look at patients with locally advanced head and neck cancer. What we haven’t seen, for the most part, when TPF is added to chemotherapy radiation, is an improvement in survival compared to chemotherapy radiation alone. So, now we have a couple of randomized trials that have addressed this issue, with chemotherapy radiation being the control arm and the experimental arm being induction chemotherapy followed by chemotherapy RT, and those trials have not shown a difference in overall survival.

More recently, a study coming out of Italy attempted the same thing and did show an improvement in overall survival. Again, induction chemotherapy followed by chemotherapy radiation improved progression-free survival and overall survival in that patient population. So, there still is some controversy around the use of induction chemotherapy. When we looked at our data, especially from the phase III trial called DeCIDE, we began to see that there may be some patients that benefit from induction chemotherapy. And those are patients with T4 disease, N2c, or N3, so still locally advanced, but very advanced squamous cell carcinoma of the head and neck. And those are the patients, at least in our practice, that we continue to use induction chemotherapy for.

The use of induction chemotherapy is definitely controversial. I think it still has to be individualized. It’s hard to make general statements that every patient benefits. In fact, I don’t think that statement is true, but I do believe that there are some patients, especially high-risk patients, that can continue to benefit from induction chemotherapy.

Jared Weiss, MD: We’ve only had one positive phase III study ever in the history of palliative head and neck oncology, and this is the EXTREME study. EXTREME randomized patients to the cisplatin/5-FU chemotherapy backbone alone or the same backbone plus the addition of cetuximab. Survival was improved from 7.4 to 10.1 months, although toxicity was rather extreme in both arms of the study, mostly related to the cytotoxic chemotherapy.

In my opinion, a palliative regimen cannot have extreme toxicity. That’s unacceptable. But I do take from the EXTREME study the lesson that cetuximab adds to cytotoxic therapy. And so in my practice, I tend to graft cetuximab on to carboplatin and paclitaxel. I like the weekly schedule, although there are many other reasonable ones. Many other practitioners will graft it on to carboplatin with 5-FU, and I think that’s also rather reasonable. I would say that for the patient with low-bulk disease that’s not imminently threatening their well-being, I also do consider single-agent therapy as opposed to three-drug therapy as a reasonable option. And, for these patients, Xeloda alone or 5-FU alone can be a good option. Telemedicine and Telesurgery in Cancer Care (TTCC) has published on this. I’ve published on this. A taxane alone can be a good option. Or for patients with truly low-bulk disease—where nothing is scaring you that it’s going to hurt the patient or take their life—cetuximab alone can be an excellent option.

Transcript Edited for Clarity
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Transcript:

Ezra Cohen, MD:
With respect to the use of chemotherapy in squamous cell carcinoma of the head and neck, we really think about it in terms of two major applications. The first is concomitant with radiation and the second is as neoadjuvant or induction chemotherapy. Let’s talk about concomitant chemotherapy first. Here we have a number of options, with probably the most standard option, or certainly the most investigated option, being high-dose cisplatin; so 100 mg/m2 given every 3 weeks. And what we know from that is that it improves survival by about 8%, an absolute improvement of 8% in survival when added to radiation therapy. It’s a modest improvement in survival, but it’s a real improvement in survival.

Along those lines, we also have data with cetuximab when added to radiation therapy alone. And, again, that appears to deliver about the same difference of about 8% to 10% improvement in overall survival at 3 and 5 years when we add cetuximab to radiation. So, from level 1 data, phase III studies, we have two validated options: high-dose cisplatin, 100 mg every 3 weeks, or cetuximab started 1 week prior to radiation and carried through the entire radiation therapy course. But, of course, there are other options that have been studied. In phase II studies, for instance, there’s a lower dose of cisplatin that has been looked at given weekly. That’s often a dose of 40 mg/m2 or sometimes 30 mg/m2, depending on the patient. And from what we can tell, that appears to be effective. It appears to be tolerable. But the reality is that it’s never been tested head-to-head against the 100 mg/m2 regimen in locally advanced head and neck cancer. I would exercise some caution when using the weekly regimen, with the realization that there isn’t level 1 evidence to support that. Other regimens include the use of carboplatin, or carboplatin and paclitaxel given on a weekly basis, cisplatin/5-FU, and some other regimens that are used at different centers. There are different options, with probably the most commonly used options being the cisplatin or the cetuximab.

In terms of induction or neoadjuvant chemotherapy, we do know a few things from phase III studies. We know that TPF—so the combination of docetaxel, platinum, and 5-FU—is superior to platinum/5-FU with respect to overall survival when we look at patients with locally advanced head and neck cancer. What we haven’t seen, for the most part, when TPF is added to chemotherapy radiation, is an improvement in survival compared to chemotherapy radiation alone. So, now we have a couple of randomized trials that have addressed this issue, with chemotherapy radiation being the control arm and the experimental arm being induction chemotherapy followed by chemotherapy RT, and those trials have not shown a difference in overall survival.

More recently, a study coming out of Italy attempted the same thing and did show an improvement in overall survival. Again, induction chemotherapy followed by chemotherapy radiation improved progression-free survival and overall survival in that patient population. So, there still is some controversy around the use of induction chemotherapy. When we looked at our data, especially from the phase III trial called DeCIDE, we began to see that there may be some patients that benefit from induction chemotherapy. And those are patients with T4 disease, N2c, or N3, so still locally advanced, but very advanced squamous cell carcinoma of the head and neck. And those are the patients, at least in our practice, that we continue to use induction chemotherapy for.

The use of induction chemotherapy is definitely controversial. I think it still has to be individualized. It’s hard to make general statements that every patient benefits. In fact, I don’t think that statement is true, but I do believe that there are some patients, especially high-risk patients, that can continue to benefit from induction chemotherapy.

Jared Weiss, MD: We’ve only had one positive phase III study ever in the history of palliative head and neck oncology, and this is the EXTREME study. EXTREME randomized patients to the cisplatin/5-FU chemotherapy backbone alone or the same backbone plus the addition of cetuximab. Survival was improved from 7.4 to 10.1 months, although toxicity was rather extreme in both arms of the study, mostly related to the cytotoxic chemotherapy.

In my opinion, a palliative regimen cannot have extreme toxicity. That’s unacceptable. But I do take from the EXTREME study the lesson that cetuximab adds to cytotoxic therapy. And so in my practice, I tend to graft cetuximab on to carboplatin and paclitaxel. I like the weekly schedule, although there are many other reasonable ones. Many other practitioners will graft it on to carboplatin with 5-FU, and I think that’s also rather reasonable. I would say that for the patient with low-bulk disease that’s not imminently threatening their well-being, I also do consider single-agent therapy as opposed to three-drug therapy as a reasonable option. And, for these patients, Xeloda alone or 5-FU alone can be a good option. Telemedicine and Telesurgery in Cancer Care (TTCC) has published on this. I’ve published on this. A taxane alone can be a good option. Or for patients with truly low-bulk disease—where nothing is scaring you that it’s going to hurt the patient or take their life—cetuximab alone can be an excellent option.

Transcript Edited for Clarity
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