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Chemotherapy, Biologics, and Other Medications

drop in intravenous (IV) drip.

Chemotherapy is the use of medications to destroy cancer cells.

Chemotherapy works by targeting cells that are dividing and growing quickly; cancer cells definitely fit into that category. However, 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. The death of normal cells is responsible for many 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 as clinical trials are conducted comparing different types of treatment plans. In the past, chemotherapy for head and neck cancers was really for palliation (relief) of symptoms in cancers that recurred after other treatment methods failed and/or to slow the progression of cancer; it was not used with the intent to cure the cancer.

Currently, chemotherapy is used in a number of different ways. For advanced stage cancers (stages III and IV), chemotherapy can be combined with another treatment approach with the goal of cure. However, it still plays an important role in palliation and treatment of head and neck cancer that has spread outside the head and neck.

Types of chemotherapy

There are a number of different chemotherapy agents. Cytotoxic medications are those that kill cells. These medications kill cells as they are dividing. Since cancer cells are dividing more quickly than other cells in the body, the chemotherapy can target cancer cells. However, many other cells in the body are constantly dividing (though not necessarily as quickly as cancer cells), so the side effects of chemotherapy are related to damage to normal cells. An example of this is hair loss (also called alopecia); these cells are constantly dividing as hair continues to grow, so the cytotoxic chemotherapy can kill hair cells along with the cancer cells.

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 might be better at treating particular types of cancer. Your doctor will discuss the details of your specific case with you.

Cisplatin is the most common type of cytotoxic chemotherapy drug used in head and neck cancer. It has been around for some time, and a number of studies have shown the benefits it can provide. Other chemotherapy agents used to treat head and neck cancer include:

  • Carboplatin
  • 5-fluorouracil
  • Hydroxyurea
  • Paclitaxel and docetaxel
  • Epirubicin

Other chemotherapies less commonly used in head and neck cancer include:

  • Gemcitabine, vinorelbine and irinotecan
  • Methotrexate and edatrexate
  • Ifosfamide

There are also other types of medications that can be used in the treatment of head and neck cancer. These are not grouped together with chemotherapy because they are more targeted drugs and are actually proteins as opposed to chemicals that take aim at other proteins found on cancer cells.

One of the newer such drugs is called cetuximab. This protein targets a specific receptor molecule that is found on some head and neck cancer cells. A number of studies have shown that using this drug in selected advanced cancers might improve 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. Other targeted therapies include drugs such as vandetanib, trametinib and bevacizumab.

Synthetic thyroid hormone is an example of another type of protein-based medication that is not a chemotherapy drug, strictly speaking, but it is used to decrease the chance of recurrence of some thyroid cancers. By taking a certain dosage of thyroid hormone by mouth every day, the brain can decrease the production of another protein in the blood called thyroid-stimulating hormone (TSH). By decreasing TSH levels in the blood, the chance of thyroid cancer returning might be decreased in certain cases. Like any medication, a doctor will need to help balance the risks of using high doses of this medication with the benefits.

You can see some general guidelines for choosing a particular chemotherapy medication below.

Administration of chemotherapy

The administration of chemotherapy is determined by a medical oncologist. The treatment plan will be made along with the rest of your cancer team, including a radiation oncologist and head and neck surgeon.

In determining your treatment plan, your medical oncologist and your cancer team will decide at what point in your treatment chemotherapy will be administered. There are a few terms of which you should be aware:

  • Induction / neoadjuvant chemotherapy: In this plan, the chemotherapy is used before another form of treatment such as surgery or radiation. The idea is to shrink the tumor and/or see the response of the tumor to the chemotherapy and then complete the treatment.
  • Adjuvant chemotherapy (with or without radiation): In this plan, the chemotherapy will be used soon after the initial treatment plan, such as surgery. In some cases of advanced cancer, chemotherapy and radiation may be given together (concurrently) after the surgery. Sometimes the decision to give chemotherapy in addition to radiation (following surgery) is only determined AFTER the pathology results from the surgery are available.
  • Definitive chemotherapy (and radiation): In this approach, chemotherapy is given along with radiation with the hope of eliminating the cancer without surgery. “Definitive chemotherapy” refers to the use of chemotherapy alone to try to cure the cancer, but this is not used in head and neck cancer (except perhaps in lymphoma). When this is used, if there is evidence that cancer is not completely gone (persistent disease), or if it comes back in the initiation area (local recurrence), you will probably require surgery as the next step.
  • Surgery after a failure of chemotherapy and/or radiation is called salvage surgery. As compared with surgery up front, salvage surgery is more difficult, may be more radical, and may involve more complications than if surgery were used initially. However, definitive chemotherapy/radiation can be just as effective and offers the possibility of avoiding surgery and keeping certain organs (organ preservation).
  • Palliative chemotherapy: In this approach, chemotherapy is given either alone or with some other form of treatment, not to cure the cancer, but to perhaps slow its growth, prevent major complications and try to improve quality of life.

Once the treatment plan is decided, you will probably have some questions about the logistics. In brief, chemotherapy is usually delivered in multiple doses; 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. But giving too much chemotherapy increases the side effects, so the right balance needs to be reached.

There are several ways to administer chemotherapy:

  • Intravenous: Most chemotherapy is administered directly into the veins (see below for techniques of intravenous administration).
  • Intra-muscular: In this technique, the chemotherapy is administered as a shot into one of the muscles in the body.
  • By mouth: Some chemotherapy drugs can be taken at home in a pill form.
  • Intra-arterial: Though not used often in head and neck cancer outside of clinical trials, chemotherapy for certain cancers can be delivered directly into an artery that feeds the cancer and delivers the chemotherapy directly to the targeted cells.
  • Transcutaneous: For some skin cancers, a patient might receive a cream to apply as a form of treatment.

When given intravenously, there are several options for getting the medications into the veins. Most commonly, when you arrive for your chemotherapy infusion appointment, a nurse will place an intravenous line (usually into your hand or arm) and this will be removed after the infusion is complete. However, longer-lasting lines might be suggested depending on your chemotherapy plan.

 

Intravenous line

 

PICC line

 

 

Hickman line

 

Port

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 you arrive 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 you typically will not go home with one of these. PICC stands for “Peripherally Inserted Central Catheter.”In this type of long-term intravenous access, the line is inserted in a small vein in the arm (just as with a normal intravenous line) without any sort of general anesthesia. The line is then guided all the way back to the superior vena cava as it empties into the heart. After the procedure, a chest X-ray may be done to confirm that the tip is in the correct place.This line can stay in for weeks. This type of long-term intravenous line is inserted by a surgeon or an interventional radiologist while you are sedated with varying amounts of anesthesia. Two skin incisions are made; one just over the vein above your collarbone, and the other in the chest. The tip of the catheter is placed into the vein at the first incision site. The other end of the catheter is tunneled under your skin and exits at the second incision site in your chest. All of the ports are hooked up to the exit end of the catheter to administer chemotherapy.This line can stay in for weeks. 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, you 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 anesthesiaThis line can stay in for weeks to many months.
Removal of an IV line is quick, simple, and painless. Removal of a PICC line takes only a minute and can be done anywhere by a nurse or someone trained to remove one. It is carefully pulled out, pressure is held for a few minutes and you are observed for a short period of time to check for any signs of bleeding. Removal of this line is done by removing the stitches securing the base to the skin and then pulling it out. Pressure is held for a few minutes, and you are observed for a short period of time to check for any signs of bleeding. Removal of this line is done by making an incision in the skin over the port. This can be done in the operating room under anesthesia or sometimes in the office.
Complications of these lines might include infection, bleeding and thrombosis (blood clot). Rarely, a pneumothorax (air in the space around the lungs) could also be a complication. Infected lines must be removed.

Frequently asked questions

  • Will I need to be admitted to a hospital to receive chemotherapy?

In many cases, chemotherapy can 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 maybe even watch television.

There are also some home infusion companies. In this case, a nurse is sent to your house, and you receive the medication at home.

Another regimen requires you to be admitted to the hospital. A nurse administers chemotherapy under the supervision of a doctor. In a hospital, the staff can monitor you more closely and manage your side effects. Sometimes the first part of treatment might be done as an outpatient, but you may require admission to a hospital to finish the later part.

  • How frequently will I need to receive the 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. In some cases, the chemotherapy might be administered once per week for three weeks. In other cases, it might be delivered three days in a row and then every week for a few weeks. It could also be administered continuously for three days. 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 continually wash your hands and have people you live with do the same.

Even if the treatment is administered to you as an outpatient, you might require temporary admission into a hospital to help you manage some of the side effects. This is particularly true if you are receiving radiation at the same time.

Side effects

You will almost certainly experience side effects from chemotherapy. While chemotherapy targets cancer cells, these medications can also cause damage to normal cells. Finding the right balance can be difficult, and your medical oncologist will speak to you about those issues.

Also, while some side effects are common to most chemotherapies, other side effects are specific to certain drugs. The most common side effects that you may experience include:

  • Mucositis: This is inflammation and ulceration of the lining of your mouth and throat. Mucositis can cause severe pain and difficulty with eating and drinking. This can happen with any chemotherapy medication, but it is more common with 5-FU. Also, when combined with radiation for head and neck cancer, this can be especially problematic.
  • 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). You should consider getting a hearing test before starting treatment with a platinum-based chemotherapy, followed by repeated hearing tests throughout your treatment.
  • Kidney problems: This is a problem with all chemotherapy drugs, including cisplatin. Carboplatin is less toxic to the kidneys than cisplatin. Your doctor will monitor your kidney function throughout your treatment course.
  • Nausea and vomiting: This is another common problem with all drugs, cisplatin more than carboplatin. You might require additional medications to help decrease nausea.
  • 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. It can also feel like an electric bolt that shoots down an arm or a leg. For some people, cancer-induced peripheral neuropathy (CIPN) is just a little bothersome and they learn to deal with it. In others, however, it can be so severe that it can lead to stoppages or reduced dosages of chemotherapy. This can be a long-term problem that can be managed with certain medications, physical therapy or even acupuncture and massage. Read more about this on the National Cancer Institute’s web site on the topic.

Other side effects might include:

  • Diarrhea / constipation
  • Low blood counts
  • Tiredness
  • Loss of appetite
  • Bleeding problems
  • Sexual and fertility changes
  • Infection
  • Urination changes
  • Swelling
  • Memory changes

Choosing the right treatment plan

According to the NCCN Guidelines®, the choice of chemotherapy should be individualized based on patient characteristics.1Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers V.1.2015. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Accessed June 18, 2015. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.  This means that the exact drugs given and how they are given might vary depending on the goals of the treatment as well as how sick/healthy you might be. 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.

Some of the recommendations provided by the NCCN Guidelines include the following:

  • If chemotherapy is a primary (initial) treatment option for your type of cancer, then the standard first line treatment is cisplatin along with radiation. This is called concurrent chemoradiation. The use of chemotherapy followed by radiation (sequential chemoradiation) is currently under study.
  • 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 not recommended to give high-dose cisplatin along with radiation after giving induction cisplatin-based therapy.

When looking at treatment recommendations by site, the NCCN Guidelines give your doctor the following guidelines.1Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers V.1.2015. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Accessed June 18, 2015. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.  These guidelines are put together by a group of experts in the field. Remember, these guidelines only fit if your cancer doctors have agreed that chemotherapy should be part of your treatment plan (which is not always the case for head and neck cancers):1Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers V.1.2015. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Accessed June 18, 2015. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.

Site of cancer

Chemotherapy Options


(If your head and neck cancer team has recommended chemotherapy as part of your treatment)

Lip
Oral cavity
Oropharynx
Hypopharynx
Glottic larynx
Supraglottic larynx
Ethmoid sinus
Maxillary sinus
Cancer with an unknown primary 
Primary chemotherapy + radiationHigh-dose cisplatin (preferred)
Cetuximab
Carboplatin/Infusional 5-FU
5-FU/hydroxyurea
Cisplatin/paclitaxel
Cisplatin/infusional 5-FU
Carboplatin/paclitaxel
Weekly cisplatin
Induction chemotherapy
(followed by surgery and/or radiation):Docetaxel/cisplatin/5-FU
Paclitaxel/cisplatin/infusional 5-FU
Induction chemotherapy
(followed by concurrent chemotherapy with radiation)Same options as above for induction, then weekly carboplatin or cetuximab for concurrent component of treatment with radiation
Nasopharynx Chemotherapy + radiation
(may be followed by adjuvant chemotherapy)Cisplatin + radiation, then cisplatin/5-FU or carboplatin/5-FU
Induction chemotherapy
(followed by radiation)Docetaxel/cisplatin/5-FU
Docetaxel/cisplatin
Cisplatin/5-FU
Cisplatin/epirubicin/paclitaxel
Induction chemotherapy (followed by concurrent chemotherapy with radiation)Same options as above for induction, then weekly cisplatin or carboplatin for concurrent component of treatment with radiation
Any Site
Recurrent, Unresectable, or Metastatic
Palliative (incurable)
Combination therapyCisplatin 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)
Carboplatin/cetuximab (nasopharyngeal)
Cisplatin/gemcitabine (nasopharyngeal) Gemcitabine/vinorelbine (nasopharyngeal)

Single agent therapy

Cisplatin
Carboplatin
Paclitaxel
Docetaxel
5-FU
Methotrexate
Cetuximab (non-nasopharyngeal)
Gemcitabine (nasopharyngeal)
Capecitabine
Vinorelbine (non-nasopharyngeal)


References

1 Referenced with permission from The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Head and Neck Cancers V.1.2015. © National Comprehensive Cancer Network, Inc 2015. All rights reserved. Accessed June 18, 2015. To view the most recent and complete version of the guideline, go online to www.nccn.org. NATIONAL COMPREHENSIVE CANCER NETWORK®, NCCN®, NCCN GUIDELINES®, and all other NCCN Content are trademarks owned by the National Comprehensive Cancer Network, Inc.