Treatment of Locally Advanced Head and Neck Cancer: Historical and Critical Review

Muhyi Al-Sarraf, MD, FRCPC, FACP


Cancer Control. 2002;9(5) 

In This Article

Abstract and Introduction

Background: Advanced squamous cell cancers of the head and neck have traditionally been associated with high rates of morbidity and mortality. Advances in management have improved outcomes for most of these patients.
Methods: The author reviews the historical progress in management of these difficult tumors and adds his own wide experience to describe and evaluate newer approaches to management.
Results: Over the last 10 years, overall survival rates for patients with head and neck cancers have improved as has quality of life. New standards of care have been defined for patients with nasopharyngeal cancer and for those with advanced unresectable disease. Organ preservation is more commonly achieved.
Conclusions: Newer targeted therapies are likely to add to the progress that has already been achieved in the multimodality management of patients with head and neck cancers.

The mode of treatment of patients with squamous cell carcinoma of the head and neck depends on the site and stage of the disease and on the overall health status of the patient. In most cases of stage I or II cancers, the single modality therapy of surgery or radiotherapy is the initial treatment of choice. Before 1980, the initial treatment of patients with locally advanced stage III or IV (M0) also would have been surgery and/or radiation therapy, a choice that also depended on the site of the disease, the resectability of the cancers, and the performance status and comorbidities of the patient. However, because of the poor results obtained with "traditional" therapy in this latter group, especially those with stage IV disease or unresectable cancers, systemic chemotherapy was introduced in the mid 1970s as part of combined modality treatment.[1,2] Later, chemotherapy was used in patients with earlier disease stages and with resectable disease for organ preservation and better cure rates. Systemic chemotherapy was usually administered with palliative intent to patients with advanced stage IV disease, M1 cancers, or recurrent disease beyond salvage local treatment.

The treatment of patients with locally advanced head and neck cancers has evolved since the introduction of combined modality treatment for these patients. Initially, a single chemotherapeutic agent such as methotrexate or cisplatin was prescribed before local definitive treatment. After that, the combination of cisplatin and bleomycin was introduced, administered as a single course before local therapy.[1,2] Later, two or three courses of cisplatin plus bleomycin were given as part of combined modality treatment. Methotrexate alone and/or vinca alkaloids (vincristine or vinblastine) were then added to the combination of cisplatin plus bleomycin.[1,2] In 1980, the combination of cisplatin and continuous infusion (96-120 hours) of 5-fluorouracil (5FU) was introduced,[1,2] which has become a widely used combination chemotherapy in patients with squamous cell carcinoma of the head and neck. Also, at approximately the same time, the concept of concurrent chemotherapy with radiation therapy was revisited, with the introduction of cisplatin given concurrently with radiation therapy as the primary treatment for patients with inoperable and/or unresectable head and neck cancers.[2]

During the last quarter of a century, clinical trials for patients with squamous cell carcinoma of the head and neck have demonstrated progress in treatment outcomes, including better local control, lower incidence of systemic recurrences, improved disease-free survival and, most importantly, improved overall survival. The quality of life has improved for many of these patients, especially when the larynx and voice function is preserved in cancers of the larynx or hypopharynx. The improvement in overall survival was demonstrated by prospective randomized phase III studies and metaanalyses and,more significantly,by population-wide statistics. The Surveillance, Epidemiology, and End Results (SEER) program at the National Cancer Institute evaluates change in cancer mortality rates in the United States. It is not generally recognized that the greatest decline in mortality rates in the period 1990 to 1997 has occurred in patients with head and neck cancers. This decline was noted for patients both above and below 65 years of age, for both men and women, and for both blacks and whites ( Table 1 ).[3]

With the introduction of new active chemotherapeutic agents and combinations,new agents given with radiation therapy, targeted treatments, and better sequencing of treatment options, it is expected that further improvements in treatment outcomes will follow.


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