Does DeCIDE give a decisive answer against induction chemotherapy in head and neck cancers?

Abstract

conductingavitalstudythatanswerssomeimportantquestionsinthe managementoflocallyadvancedheadandneckcancers.Thenegative resultsoftheDeCIDE(DocetaxelBasedChemotherapyPlusorMinus InductionChemotherapytoDecreaseEventsinHeadandNeckCancer) and the PARADIGM (Induction Chemotherapy Followed by Concurrent Chemoradiotherapy [sequential chemoradiotherapy] Versus Concurrent Chemoradiotherapy Alone in Locally Advanced Head and Neck Cancer) studies have undoubtedly tempered the initial enthusiasm for induction chemotherapy that was generated after the results of the TAX studies (which showed improved outcomes with triplet induction chemotherapy over the traditional cisplatinflurouracil doublet) were published. 2-4 Although the negative results of the Cohen et al 1 study may be related to the potential confounding influence of human papillomavirus‐positive oropharyngeal cancer, some further methodologic issues may also explain the results. The study was performed on the premise that induction chemotherapy before concurrent chemoradiotherapy (CRT) may improve survival by reducing the distant metastasis rate in a subgroup of patients felt to be at a higher risk of distant metastasis. However, the risk ofmetastasismaynotbethesameinallpatientswithN2nodaldisease. AmajorityofthepatientsintheCohenetal 1 studyhadN2bandstage IVA disease. The patient population with the greatest risk of distant metastasis (ie, those with N3 disease) was under-represented and accounted for just over 10% of the patient population. In an interesting study, Garden et al 5 demonstrated that in patientswithearlyT-stageoropharyngealcancerswhoareconsideredto have advanced disease because of the presence of lymphadenopathy, little is gained from adding chemotherapy to radiation alone in terms of locoregional control. In that study, approximately 50% of the patients had T1 and T2 primaries. This is probably not the population that should be subjected to more intensified treatment in the form of induction chemotherapy followed by CRT. Another reason for the lack of effect as seen in this study may havebeenpoorcompliancewithtreatment.Approximately94%of the patients randomly assigned to the CRT arm completed their treatment as compared with only 85% of the patients randomly assigned to the induction chemotherapy arm. This difference of nearly 9% was probably enough to eliminate any gains made by induction chemotherapy. Furthermore, the manuscript provides no data regarding the delay in starting CRT in patients receiving neoadjuvant chemotherapy (NACT). Only 79% of patients received the intended two doses of NACT. The dual factors of delay