Familial Nasopharyngeal Carcinoma 6

The Intergroup 0099 Trial for Nasopharyngeal 12Cancer: History, Perceptions, and TransitionsJay S. Cooper“Because the nasopharynx is immediately adjacent tothe base of the skull, surgical resection of the neoplasmwith an acceptable margin is impossible; hence, radiationtherapy has been the sole treatment for carcinoma of thenasopharynxCarlos Perez (1997) Principles and Practice of RadiationOncology, 3rd edn, p 909”CONTENTS12.1 Introduction 16112.2 Traditional Therapy 16112.3 Radiotherapy Evolution: From 2½D to 3Dto IMRT 16212.3.1 Target Localization Limitations 16212.3.2 State of the Art Circa 1980 16212.4 Chemotherapy: A Potential Ally 16312.4.1 Suggestive Evidence of ChemotherapyEffect 16312.5 Intergroup 0099: The Details 16412.5.1 Intergroup 0099: The Good News 16412.5.2 Intergroup 0099: The Limitations 165References 165Jay S. Cooper, MD, FACR, FACRO, FASTRODepartment of Radiation Oncology, Maimonides Cancer Center,6300 Eighth Avenue, Brooklyn, NY 11220, USA12.1IntroductionIn recent years, the management of locoregionallyadvanced nasopharyngeal cancer has evolved quickly.Radiation therapy, delivered alone, was generallyconsidered to be the only potentially curative therapyfor this tumor only a brief time ago. How times havechanged! The volume of data that demonstratespotential contributions of chemotherapy to the managementof nasopharyngeal cancer is now substantial;however, many questions about the precise roleof chemotherapy remain unanswered. The purposeof this chapter is to look back briefly at the state ofclinical practice one to two decades ago, survey thebenefits and limitations of radiation therapy as it wasadministered then, review the essential details of theIntergroup 0099 landmark trial (which providedprospective randomized data supporting the use ofchemotherapy), and evaluate critically what welearned and did not learn from that trial.12.2Traditional TherapyLess than two decades ago, following radiation therapyalone, patients who had stage III or IV nasopharyngealcancer generally had a substantial incidence(50%–80%) of local recurrence (Hoppe et al. 1976;Mesic et al. 1981; Perez et al. 1969; Scanlon et al.1967; Cooper et al. 1983; Ahmad and Stefani 1986;Dimery et al. 1979) and a relatively high (approximately30%) risk of distant dissemination of disease.To some degree, the failure of radiation therapy couldbe attributed to late diagnosis resulting in the discoveryof some tumors that were so large or so resistantto radiation that any attempt would fail and to some