Monoclonal Antibody
The only monoclonal antibody drug that is FDA approved is Cetuximab. This antibody targets the epidermal growth factor receptor on the cell surface of cancer cells. A number of studies have shown that using this drug in certain advanced cancers improves local control and survival. Currently, cetuximab can be combined with either chemotherapy for recurrent and/or metastatic squamous cell carcinoma or combined with radiation in the initial treatment of advanced squamous cell cancer.
Immunotherapy
Immunotherapy is another type of treatment for head and neck cancer. The body’s immune system plays a critical role in eradicating cancer from the body. Immunotherapy includes a group of targeted drugs that enhance the immune system’s ability to fight cancer. Examples of immunotherapy drugs used for the treatment of head and neck cancers include Pembrolizumab and Nivolumab. These are both FDA approved for patients with advanced or metastatic squamous cell carcinoma who are not candidates for curative radiation or surgery. There are ongoing investigations to determine if these drugs can be used for other treatments.
Cemiplimab is another example of immunotherapy used for treatment of head and neck cancers. It was approved by the FDA in 2018 for patients with advanced or metastatic cutaneous squamous cell carcinoma who are not good candidates for curative radiation or surgery. Other targeted therapies include drugs such as vandetanib, trametinib, bevacizumab, as well as, several other immunotherapy drugs that are currently under investigation.
Chemotherapy
Chemotherapy is the use of medications to destroy cancer cells. There are multiple types of chemotherapy that work by a variety of mechanisms; however, in general, chemotherapy works by targeting cells that are dividing and growing quickly. Cancer cells definitely fit into that category. Some normal cells are also constantly dividing, including cells in the bone marrow, cells that line the mouth, throat and digestive tract, and cells responsible for hair growth. While surgery and radiation are directed at the specific site where cancer cells are known to exist, chemotherapy is delivered through the blood to the entire body and thereby can impact the growth and destruction of cancer cells anywhere that they exist. The death of normal cells is one of the side effects of chemotherapy.
The role of chemotherapy for head and neck cancer has changed quite a bit as new medications are discovered and clinical trials are conducted comparing different types of treatment plans. In the past, chemotherapy for head and neck cancers was most commonly used for palliation (relief) of symptoms in cancers that recurred after other treatment methods failed and/or to slow the progression of cancer, rather than with the intent to cure the cancer.
Currently, chemotherapy is used for advanced-stage cancers (stages III and IV), in combination with another treatment approach with the goal of cure. It is also sometimes given to shrink the cancer prior to curative treatment. Chemotherapy still plays an important role in palliation and treatment of cancer that has spread outside the head and neck.
Types of Chemotherapy
There are many different types of chemotherapy medications. They differ in how they kill the cancer cells. The choice of medication(s) is based on the trials that have shown which ones are effective. In some cases, different types of chemotherapy drugs might be used together. While this might worsen side effects, it has been shown to be better at treating particular types of cancer. Doctors will discuss the details of a specific treatment plan with their patient.
Cisplatin is the most common type of cytotoxic chemotherapy drug used in head and neck cancer. It has been used for some time, and a number of studies have shown the benefits it can provide in certain scenarios.
Other Chemotherapy Agents That Treat Head & Neck Cancer
- Carboplatin
- 5-fluorouracil (5-FU)
- Paclitaxel and docetaxel
- Gemcitabine
- Methotrexate
Administration of Chemotherapy
Chemotherapy is administered by a medical oncologist. The medical oncologist will develop a treatment plan with the rest of the patient’s cancer care team, including a radiation oncologist and head and neck surgeon. This decision might be made during “tumor board,” a meeting in which a team of doctors who specialize in the management of head and neck cancers collaborate and discuss their most difficult cases. Tumor board meetings allow for specialists across all fields of cancer care to contribute their own expertise, which provides a patient’s doctor with a well-rounded and clearly defined treatment plan for their patient.
In determining a treatment plan, a medical oncologist and cancer care team will decide at what point in a patient’s treatment chemotherapy will be administered.
Important Terms
Induction / Neoadjuvant Chemotherapy
In this plan, the chemotherapy is used before another form of treatment such as surgery or radiation. The goal is to shrink the tumor and/or see the response of the tumor to the chemotherapy and then to complete the treatment. In most circumstances, induction chemotherapy is administered prior to a definitive course of chemotherapy and radiation, but there are different scenarios in which induction chemotherapy can be combined with both surgery and radiation.
The most common regimen used in induction chemotherapy for head and neck cancers is a three drug regimen called TPF (Docetaxel, Carboplatin and Fluorouracil induction).
Primary Chemotherapy & Radiation (Chemoradiation)
In this approach, chemotherapy is given along with radiation as the primary treatment with the goal of eliminating the cancer without needing surgery.
Adjuvant Chemotherapy (with Radiation)
In this plan, the chemoradiation will be initiated after surgery for patients who are considered to have a higher risk of recurrence following surgery. A patient’s risk of recurrence depends on a number of pathologic variables including positive margins and extranodal extension. The decision to administer chemoradiation is only determined AFTER the pathology results for the surgery are available.
Palliative Chemotherapy
In this approach, chemotherapy is given either alone or with some other form of treatment. The goals of palliative chemotherapy are to slow tumor growth, minimize symptoms, improve quality of life, and ultimately prolong the patient’s life.
Chemotherapy is usually delivered in multiple doses over defined periods of time and with recovery periods in between; this is because each administration of chemotherapy kills a certain percentage (or fraction) of cancer cells. By giving more doses of chemotherapy, more of the cancer cells are destroyed. Giving too much chemotherapy increases the side effects, so the right balance needs to be reached.
Ways to Administer Chemotherapy
Orally (By Mouth)
Some chemotherapy drugs can be taken at home in a pill form.
Intravenous
Most often chemotherapy is administered directly into the veins. When given intravenously, there are several options for getting the medications into the veins. Most commonly, when a patient arrives for their chemotherapy infusion appointment, a nurse will place an intravenous line (usually into the hand or arm) and this will be removed after the infusion is complete. However, longer-lasting lines might be suggested depending on the chemotherapy plan.
- Intravenous line
This type of line provides short-term access to a vein for administration of medications. Typically, it is inserted by a nurse on the day the patient arrives for chemotherapy and is removed at the end of the session. No anesthesia is required for insertion or removal. This line should not stay in for more than a few days before being changed, and a patient typically will not go home with an intravenous line. - Port
A port is another type of central venous line. There are many brand names. One advantage of a port is that the device is buried completely under the skin, with no lines coming out. So, once the scars are healed after the insertion, the patient can get the area wet. This device is inserted by a surgeon or an interventional radiologist with some local anesthesia and sedation or with general anesthesia. It can stay in safely for several weeks to many months.
Infrequent complications of these lines might include infection, bleeding and thrombosis (blood clot).
Side Effects
A patient will almost certainly experience side effects from chemotherapy. While chemotherapeutic agents target cancer cells, these medications can also cause damage to normal cells.
Finding the right balance can be difficult, and a medical oncologist will speak to the patient about those issues. Also, while some side effects are common to most chemotherapies, other side effects are specific to certain drugs.
Common Side Effects
- Mucositis
This is inflammation and ulceration of the lining of the mouth and throat. Mucositis can cause pain and difficulty with eating and drinking. This can happen with any chemotherapy medication, especially when combined with radiation for head and neck cancer. - Hearing Loss
This is a special risk factor for platinum-based chemotherapy drugs, such as the commonly used cisplatin. Associated symptoms might include ringing in the ears (tinnitus). Patients should consider getting a hearing test before starting treatment, followed by repeated hearing tests throughout their treatment. - Kidney Problems
This is a problem with multiple chemotherapy drugs, including cisplatin. Carboplatin is less toxic to the kidneys than cisplatin. A doctor will monitor a patient’s kidney function throughout their treatment course. - Nausea & Vomiting
This is another common problem with many chemotherapy drugs. Patients often will receive medications prior to administration of chemotherapy to decrease risk of experiencing nausea and vomiting. - Rash
Rashes can occur with a variety of drugs, including 5-FU. However, cetuximab therapy is particularly known for this problem. With cetuximab, the rash looks similar to acne. Fortunately, the rash goes away after stopping treatment, and there is no significant pain or problems related to rashes in most cases of cetuximab. - Neuropathy
This is a nerve problem that usually starts as a feeling of numbness or tingling in the fingers or toes. For some people, chemotherapy-induced peripheral neuropathy (CIPN) is only mildly bothersome; however, in others, it can be severe enough to lead to stopping or reducing the dose of chemotherapy. This can also be a long-term problem that can be managed with certain medications, physical therapy, or even acupuncture and massage.
Additional Side Effects
- Diarrhea / constipation
- Low blood counts
- Fatigue
- Loss of appetite
- Bleeding problems
- Sexual and fertility changes
- Infection
Treatment Plan
The choice of chemotherapy should be individualized based on patient characteristics. This means that the exact drugs given and the route by which they are given vary depending on the goals of the treatment as well as how sick/healthy the patient is.
Also, there are always clinical trials going on to try new combinations and sequences of treatments to improve the chance of cure, prolong life, prevent distant metastases and/or improve quality of life.
Concurrent Chemoradiation
If chemotherapy is a primary (initial) treatment option for a patient’s type of cancer, then the standard first line treatment is often cisplatin along with radiation. This is called concurrent chemoradiation.
Induction Chemotherapy
If induction chemotherapy is recommended, then the next treatment steps after chemotherapy could be radiation alone, cetuximab with radiation or carboplatin with radiation. It is generally not recommended to give high-dose cisplatin along with radiation after giving induction cisplatin-based therapy.
These guidelines are put together by a group of experts in the field. Remember, these guidelines only fit if doctors have agreed that chemotherapy should be part of their patient’s treatment plan, which is not always the case for head and neck cancers.
Treatment Plan by Cancer Site
Oropharynx & Hypopharynx; Glottic & Supraglottic Larynx; Ethmoid & Maxillary Sinus; Lip & Oral Cavity*; Cancer with an Unknown Primary Site
Primary Chemoradiation
- High-dose cisplatin
- Weekly cisplatin
- Weekly carboplatin
- Cetuximab
- Cisplatin/paclitaxel
- Carboplatin/paclitaxel
Induction Chemotherapy
Docetaxel/cisplatin/5-FU –or– Paclitaxel/cisplatin/infusional 5-FU
- Followed by surgery or radiation.
- Followed by weekly carboplatin or cetuximab with concurrent radiation.
*Lip and oral cavity cancers are very rarely treated with primary chemotherapy. Primary chemotherapy is only used for these cancers when the tumors are unresectable.
Nasopharynx
Chemoradiation
Cisplatin + radiation followed by either cisplatin/5-FU or carboplatin/5-FU
- May then be followed by adjuvant chemotherapy.
Any Site with Recurrent, Unresectable or Metastatic Disease; Palliative (incurable)
Combination Therapy
- Cisplatin or carboplatin + 5-FU + cetuximab (non-nasopharyngeal)
- Cisplatin or carboplatin + docetaxel or paclitaxel
- Cisplatin/cetuximab (non-nasopharyngeal)
- Cisplatin/5-FU
- Cisplatin/docetaxel/cetuximab (non-nasopharyngeal)
- Cisplatin/paclitaxel/cetuximab (non-nasopharyngeal)
- Cisplatin/gemcitabine (nasopharyngeal)
Single Agent Therapy
- Cisplatin
- Carboplatin
- Paclitaxel
- Docetaxel
- 5-FU
- Methotrexate
- Cetuximab (non-nasopharyngeal)
- Gemcitabine (nasopharyngeal)
Frequently Asked Questions
Will I need to be admitted to a hospital to receive chemotherapy?
In most cases, chemotherapy will be delivered on an outpatient basis. This means you go to a special chemotherapy infusion center for the day, a nurse places an intravenous line and you sit and receive the medication. You can read, listen to music and/or watch television.
How frequently will I need to receive chemotherapy and for how long?
The exact treatment regimen will be determined by your doctor and may change from the original plan depending on what type of side effects you have and how the tumor responds. Most often chemotherapy is given weekly or every three weeks. Your doctor will talk to you about the regimen that is best for you.
What other changes in routine should I expect?
Depending on the location of your cancer, additional treatment and the side effects you experience, your doctors might recommend you receive a feeding tube. This is to help you maintain your nutrition as you go through treatment. Also, while you are receiving chemotherapy, you might be at an increased risk of getting an infection. You should make sure to wash your hands frequently and have people you live with do the same.
