RADIOTHERAPY-CHEMOTHERAPY COMBINATIONS IN HEAD AND NECK SQUAMOUS-CELLCARCINOMA - OVERVIEW OF RANDOMIZED TRIALS

Over the past 30 years, numerous randomized phase III trials have been conducted for head and neck squamous cell carcinomas (HNSCC) to evalu ate the tolerance and efficacy of radiotherapy-chemotherapy (RT-CT) co mbinations. The majority of these trials covered locally advanced, oft en inoperable carcinomas, for which conventional RT offers mediocre re sults in terms of loco-regional control. The adjunction of CT was supp osed to enhance the ''antitumor'' cytotoxic effect of RT and preclude or delay the emergence of distant metastases. CT was mainly used befor e RT (neoadjuvant) or concomitantly (1). Although phase II results hav e often been promising, few randomized trials have demonstrated the st atistically significant benefit of combining RT-CT compared to RT alon e in terms of loco-regional control, rate of distant metastasis, and o verall survival. However the few studies which demonstrated a statisti cally difference generally exhibited a difference in favor of the CT a rm (Tables I to V). The benefit linked to the use of CT is therefore l ow enough to be undetectable in the majority of trials, and it can be estimated that the overall gain in terms of survival is probably in th e range of 4-8% (1,2). It is noteworthy that the majority of randomize d trials do not have the statistical power capable of demonstrating su ch a difference. This article presents the main randomized trials cond ucted for HNSCC, for which patient inclusion occurred between 1965 and 1993, comparing RT alone vs RT combined with CT. This review does not include randomized trials in which the loco-regional treatment was ma inly surgery (+/- RT). However we have retained those trials in which CT was used concomitantly with post-operative RT as well as the so-cal led ''organ preservation'' trials.