Management of Cancer of the Head and Neck
Chemotherapy: General Guidelines

Chemotherapy has been used in head and neck cancer in a variety of settings. It has been used as initial "neo-adjuvant" therapy prior to radiation therapy when organ preservation is a goal. It has been used concurrently with radiation therapy in locally advanced tumors where it has been shown to improve local control and decrease the risk of distant recurrence. It has been used after definitive surgery and radiation as an "adjuvant" therapy in patients felt to be at high risk for recurrence, and it has been used as palliative therapy in patients with advanced unresectable or metastatic disease.

Most chemotherapeutic agents have been investigated in head and neck cancers. To date, the agents found to be most effective include cisplatinum, carboplatinum, taxanes, 5-fluorouracil, methotrexate, and ifosphamide. These agents have been used alone or in combination in a variety or regimens. The agents vary in their single agent response rate and toxicity.

Initial evaluation of the patient by the medical oncologist requires a detailed history and physical examination, as well as consultation with the head and neck surgeon and radiation oncologist to optimize care for the individual patient. In addition to assessing the stage and extent of the cancer via physical exam and appropriate radiographic studies, the medical oncologist must evaluate the overall health of the patient with attention to performance status, organ function and co-morbid conditions which might affect the ability to use some chemotherapeutic agents. Careful nutritional assessment prior to therapy is essential.

Once the patient has been assessed by the multidisciplinary team, a treatment plan is outlined. If organ preservation is one of the goals of treatment, chemotherapy given prior to radiation therapy has been shown to be useful in selecting those patients who are more likely to benefit from radiation and, thus, achieve organ preservation. More recently it has been shown that chemotherapy given with radiation can improve the chances for local control of cancer and decrease the risk of distant metastases. The optimal chemotherapy combination for either of these situations has not yet been defined and this is an area of very active clinical investigation. In general, patients who have resectable cancers but desire organ preservation should be enrolled in clinical trials if they are available.

In the setting of advanced, unresectable cancers, recurrent or metastatic cancer, chemotherapy is often used for palliation. Most single agents produce objective tumor response rates of 15-35%. Combination chemotherapy regimens have produced higher response rates but no clear benefit in terms of patient survival. The medical oncologist must assess the performance status of the patient, and his or her previous treatment prior to recommending a specific agent or combination.

Side effects from chemotherapy may be acute or long term. Common side effects include fatigue, myelosuppression with risk of infection, nausea and hair loss. Cisplatinum can cause renal failure and ototoxicity. The platinum analogs and taxanes can have neurotoxicity including paresthesias and painful peripheral neuropathy. Some agents have mucosal toxicity, which can be worse when they are given with or after radiation therapy. Mucosal toxicity is common with 5-fluorouracil and methotrexate and can also be seen with taxanes. Medical oncologist must be aware of these and other less common problems when evaluating and treating patients with head and neck cancers.

Due to the location of their tumors and the mucosal effects of therapy, many patients with head and neck cancer are nutritionally compromised. If highly toxic therapy is planned, placement of a PEG tube prior to starting therapy enables patients to maintain nutrition during therapy and recover more quickly. Whether or not a PEG is in place, the patient's intake and nutritional status should be assessed on a regular basis during therapy with appropriate intervention in a timely fashion.