Introduction
The incidence of head and neck cancer in the United States was more than 37000 in the year 2003. It is estimated that 11000 deaths occur annually due to head and neck cancer. The recovery rates for severe cases of head and neck cancer are poor. The emerging new treatment technique emphasizes using radiotherapy with concurrent chemotherapy called combined therapy. Combined therapy focuses on preserving the organ resulting in overall survival that ensures prolonged life. Previously cisplatin combined with 5-Fluorouracil was used to treat head and neck cancer. Later studies showed that Cisplatin chemotherapy is associated with neurological toxicity. Therefore, advancement in combination regimens introduced new agents such as Docetaxel and Paclitaxel.
What Is Docetaxel?
Docetaxel belongs to the group of taxanes. Taxane is derived from plants of the genus Taxus. Docetaxel treats breast, lung, stomach, prostate, head, and neck cancer. Docetaxel is semi synthesized taxane that promotes cell division. Docetaxel shows anti-tumor activity in head and neck cancer. The maximum dose of Docetaxel administered is 100mg/m2 every 21 days (The dose of Docetaxel is typically given in milligrams per square meter of body surface area. A body surface area of 1 square meter is equivalent to a person's body weight of approximately 70 kg and a height of 1.7 meters). Docetaxel can be given weekly at a dose of 30 to 35 mg/m2. This drug has shown an excellent response to antitumor activity with reduced toxicity. Therefore, studies have shown Docetaxel effectively treats head and neck cancer.
Docetaxel has shown a response of 20 to 40 percent in cases of head and neck cancer when administered as a single therapy. Docetaxel is combined with several drugs, such as Cisplatin and 5-Fluorouracil. The multidrug regimen incorporating Docetaxel improves the response rate to 90 percent. Few clinical trials show high response rates when Docetaxel is administered intravenously at 100mg/m2 for one hour, followed by Cisplatin at 75mg/m2. Neutropenia is the major toxicity of this regimen.
What Is the Role of Docetaxel for Concurrent Chemoradiation?
The combination of radiation therapy with chemotherapy has shown disease-free survival with decreased reoccurrence. Chemoradiation improves tumor response through a radiosensitizing mechanism which enhances radiation effects. Docetaxel is a radiosenstizing agent. Radiosenstitizing agent makes cancer cells more vulnerable to radiation therapy, thereby help in shrinking tumor size. Docetaxel induces a change in apoptosis (programmed cell death) and enhances tissue oxygenation contributing to radiosensitizing properties. Docetaxel blocks the cell cycle of cancerous cells, and radiation therapy uses high energy to destroy the tumor. A three-week administration schedule for this regimen is recommended. However, both weekly and three-week administration is effective. In clinical trials, those patients with head and neck cancer who have a poor prognosis receive chemoradiation. The response rate for this combined therapy was excellent. Studies have shown the maximum tolerated weekly dose of Docetaxel in combination with radiation was 25 mg/m2. A higher dose is associated with certain toxicities, such as mucositis and dermatitis. Therefore, the optimal dose of Docetaxel ranges from 20 to 25 mg/m2 when combined with radiation therapy.
What Are the Side Effects of Chemoradiation?
The introduction of chemoradiation shows an excellent response in anti-tumor activities but at the expense of toxicities such as dermatitis, mucositis, and neutropenia. The administration of low doses of Docetaxel combined with radiation can also treat the tumor with fewer toxicities. Docetaxel, when given subcutaneously, has few toxic reactions over the intravenous route, such as the late onset of rashes on the skin or episodes of nausea accompanied by headache.
-
Neutropenia - Neutropenia is the condition in which decreased number of neutrophils (white blood cells) are found in the blood. Neutropenia is characterized by the increased risk of infection as white blood cells function as a defense system in our body to fight against infection. Neutropenia is the hematological side effect of Docetaxel combined with radiotherapy.
-
Alopecia - It refers to a condition associated with complete hair loss from the head or other body parts. Alopecia can cause complete or partial baldness.
-
Mucositis - The mucus membrane is the lining that covers our visceral organs and body parts. The condition in which inflammation occurs in the mucus membrane causing painful ulceration (ulcer), is called mucositis. Mucositis can occur anywhere, including the gastrointestinal tract, mouth, and skin. It is an adverse effect of chemotherapy in cancer patients. Mucositis is an important acute side effect of chemoradiotherapy. Mucositis is treated by aggressive pain management along with intravenous fluid administration.
-
Dermatitis - The condition characterized by red and itchy skin.
-
Fatigue - Patients feel lethargy, and they get tired easily. This condition affects daily chores resulting in diminished quality of life.
-
Sensory Neuropathy - A disease in which demyelination (a condition in which the protective sheath of a neuron gets damaged) of neurons (unit of the nervous system) occurs, causing immobilization of the limbs.
-
Fluid Retention Syndrome - It is a symptom of an underlying disease causing abdominal pain, headache, diarrhea, and blurred vision.
-
Asthenia - A condition in which loss of muscle strength occurs.
-
Esophagitis - A condition in which inflammation of the food pipe occurs, causing difficulty in ingesting food. Sometimes in severe esophagitis, the administration of gastrotomy food tubes helps the patient to feed.
-
Pneumonitis - It is a lung infection characterized by shortness of breath, cough, and fatigue.
How Can Toxicity of Chemoradiation Be Prevented?
The use of Amifostine can prevent the toxicity of chemoradiation without compromising the response rate for anti-tumor activities. Amifostine is administered and well tolerated by subcutaneous route. Patients with advanced head and neck cancer can be treated by chemotherapy, including Cisplatin and Docetaxel, given every 21 days, followed by radiation therapy weekly. Amifostine can be given subcutaneously 30 minutes to one hour before radiation to prevent combined therapy's toxicity.
Conclusion
Docetaxel has radiosensitizing properties. Docetaxel has shown excellent response as an anti-tumor activity when combined with other regimens without toxicities. Current studies recommend that Docetaxel can be administered at a dose of 20 to 30 mg/m2 weekly, followed by radiation therapy which is highly effective. The subcutaneous route is well tolerated. The modulation in chemoradiation introduces a radioprotective agent to prevent the toxicities of combined therapy. Patients with head and neck cancer, when administered with Docetaxel followed by radiation, show excellent prognosis. Chemoradiation helps to achieve disease-free survival with the preservation of the organ.
