Transcript:Jared Weiss, MD: Adjuvant therapy is indicated for high-risk surgical cancer. So, certainly, if there are positive or close surgical margins or an extracapsular extension, it’s absolutely mandatory to give adjuvant radiotherapy. In my practice, we look to T3, T4 tumors, as well, for an indication, certainly at least N2a tumors. In my opinion, any node-positive tumor, high depth of invasion is an important risk factor that I think standardly we add radiation for. And, then there are other risk factors that you can strongly consider it for, such as lymphovascular space invasion.
Once a decision is made to use adjuvant radiotherapy, for almost any patient, the addition of systemic therapy can improve local control. What’s more controversial is for which patients this translates into an improved survival. So, this comes down to the question of when to add chemotherapy, and what to add. The most standard answer here is for extracapsular extension or for positive margins, we need to add systemic therapy to our adjuvant radiation. However, I think in practice, for a young, healthy, motivated patient, it’s quite reasonable to add chemotherapy under other high-risk situations, so very, very high-bulk disease, lymphovascular space invasion, and other risk factors. In terms of what to add, there’s only one truly, well validated regimen and that’s high-dose cisplatin 100 mg/m2 given every 3 weeks for 3 total doses. This is a very rough regimen to get through with high rates of emetogenicity, nephrotoxicity, and autotoxicity, including both high-frequency hearing loss and tinnitus, as well as neuropathy. And, there are supportive care maneuvers that we’ll discuss that can help to get a patient through that.
The vast majority of incurable head and neck cancers gets there through multiple failed attempts at cure. The majority of presentation is locally advanced disease. That patient may get induction chemotherapy, chemotherapy radiation, a salvage surgery or sometimes even re-irradiation. And, at the time of reaching incurable, the disease may still only be locally advanced and not metastatic. So, very often, radiation, at least to the primary site, is not available to us anymore as part of palliative therapy. Where I think it’s very applicable is that several percent of incurable cancer that starts as metastatic disease. And, here, local control at that primary site still matters a lot. The primary site can be a major source of pain and suffering, a major source of morbidity for the patient, and controlling it matters. That’s when palliative radiotherapy can have its greatest use. There are a variety of ways to do this one regimen—that I find particularly helpful—the so-called, Quad-shot regimen, which is BID radiation for 2 days. And, if you follow that with your systemic therapy, you often never need to repeat it, although you can.
Chemotherapy can be added to definitive radiotherapy to improve local regional control and cure it. In standard practice, we do this for locally advanced T stage. In my practice, this is T3 or T4, occasionally for a very big T2 with other dangerous factors—and for node-positive disease. When chemotherapy is added, the most standard regimen to add is cisplatin at a dose of 100 mg/m2 given every 3 weeks. This is a very rough regimen. There’s high rates of emetogenicity. You can ameliorate that somewhat through the use of aggressive antiemetic strategies. So, in my practice, fosaprepitant, steroids, we tend to use dexamethasone, a 5-HT3 antagonist. Perhaps, now there’s new data that a low-dose antipsychotic, as well, can help. And, then we use dexamethasone several days after in a taper to help control nausea. Ginger can also help a little bit, and we give patients as-needed medicines at home, typically, ondansetron and prochlorperazine. This regimen is also very nephrotoxic. You can ameliorate that with IV fluid before and after. We give it 2 subsequent days in the week. You ask patients to remain well hydrated. There are data that the drug, Mannitol, can also be nephroprotective. Cisplatin is also very neurotoxic, causing peripheral neuropathies and other weird neuropathies. There’s not a lot you can do to protect against these. You mostly treat them after they happen. I wish I were done. It’s also a very autopathic drug causing high-frequency hearing loss and tinnitus, as well.
There are alternatives. The best validated alternative is probably, cetuximab. There’s a large phase III study, the Bonner trial that randomized patients to receive radiation alone, or radiation plus this EGFR monoclonal antibody, cetuximab. Survival was improved with the addition of cetuximab to radiation therapy. Its most common side effects are a papular, pustular rash; it looks like acne. And uniquely, in the southeast of the United States, there is a roughly 20% anaphylaxis rate with the first infusion. This can be dealt with by giving Benadryl and steroids before. Further, there’s a cancer paper in press showing that there’s an Alpha-Gal assay that has negative predictive value against these anaphylactic reactions.
If neither of these drugs are possible, there are a variety of regimens used in clinical practice, but with very low levels of validation. Weekly cisplatin at a dose of 30 or 40 mg/m2 is commonly used in the United States. And bolus carboplatin, while it has very little data behind it, is certainly reasonable if there isn’t another alternative.
Transcript Edited for Clarity