Chemotherapy - Head and neck cancer

Overview
The role of chemotherapy in the primary treatment of locally advanced head and neck cancer has become established in certain clinical settings. These include the definitive treatment of nasopharyngeal carcinoma and in organ preservation protocols for laryngeal and hypopharyngeal tumors. It also plays a role in the palliation of recurrent disease.

Research into breast, lung, prostate, and colon cancers benefits from large, relatively homogeneous study groups. HNSCC research, on the other hand, suffers from great disease heterogeneity and a relatively low incidence in the United States, factors contributing to confusion and conflicting reports regarding chemotherapy outcome (response and survival) and underscoring the importance of large multicenter randomized chemotherapy trials. Large-scale studies of laryngeal and nasopharyngeal cancers are demonstrating the importance of multicenter studies of specific HNSCC sites.

Prognostic Factors
Prognostic factors for chemotherapy response generally accepted as standard include performance status, nutritional status, degree of tumor differentiation, tumor burden (size of primary tumor, resectability, and extent of regional nodal metastases), disease stage, and primary cancer site. In head and neck cancer, however, correlative results are conflicting, and it is difficult in most cases to say which of these standard factors has significant effects on response. One clear exception relates to site; undifferentiated nasopharyngeal cancer is the most responsive and adenoid cystic salivary gland cancer the least responsive to chemotherapy. Recent work looking for additional prognostic factors in HNSCC has focused on immunologic studies, tumor DNA content, p53, thymidylate synthase, glutathione S-transferase, and GADD 153.

Chemotherapy Response
Comparing the results of HNSCC chemotherapy trials can be difficult because of inconsistent standards for response determination. Confusion regarding tumor measurements can arise as a result of superinfection from ulcerative lesions or, in studies in recurrent disease, from scarring after local therapy. The timing of response determination also varies. Clinical response determinations 4 to 6 weeks after therapy often describe persistent nonmalignant abnormalities (eg, fibrosis, edema) that resolve after longer follow-up. This is a problem with bulky tumors treated with chemoradiotherapy.

Complete response to chemotherapy is of overwhelming importance to a patient's survival outlook. Response reporting in primary HNSCC trials differentiate between responses at primary sites and those at regional sites. Pathologic documentation of primary-site clinical complete response is critical, and the number and depth of biopsies must be rigorously defined. There is disagreement, however, as to the comparative importance of histologic and clinical complete responses. Much of the discrepancy in this area of research may relate to a lack of thoroughness in clinical staging and a lack of uniform specifications for the number and depth of postchemotherapy biopsies. Although critical in screening for new drug activity, partial responses generally do not increase survival in primary or recurrent disease.