Randomized trial of radiation therapy versus concomitant chemotherapy and radiation therapy for advanced-stage oropharynx carcinoma

Background: We designed a randomized clinical trial to test whether the add ition of three cycles of chemotherapy during standard radiation therapy wou ld improve disease-free survival in patients with stages III and IV (i.e., advanced oropharynx carcinoma). Methods: A total of 226 patients have been entered in a phase III multicenter, randomized trial comparing radiotherapy alone (arm A) with radiotherapy with concomitant chemotherapy (arm B), Rad iotherapy was identical in the two arms, delivering, with conventional frac tionation, 70 Gy in 35 fractions. In arm B, patients received during the pe riod of radiotherapy three cycles of a 4-day regimen containing carboplatin (70 mg/m(2) per day) and 5-fluorouracil (600 mg/m(2) per day) by continuou s infusion. The two arms were equally balanced with regard to age, sex, sta ge, performance status, histology, and primary tumor site, Results: Radioth erapy compliance was similar in the two arms with respect to total dose, tr eatment duration, and treatment interruption, The rate of grades 3 and 4 mu cositis was statistically significantly higher in arm B (71%; 95% confidenc e interval [CI] = 54%-85%) than in arm A (39%; 95% CI = 29%-56%), Skin toxi city was not different between the two arms. Hematologic toxicity was highe r in arm B as measured by neutrophil count and hemoglobin level. Three-year overall actuarial survival and disease-free survival rates were, respectiv ely, 51% (95% CI = 39%-68%) versus 31% (95% CI = 18%-49%) and 42% (95% CI = 30%-57%) versus 20% (95% CI = 10%-33%) for patients treated with combined modality versus radiation therapy alone (P =.02 and .04, respectively), The locoregional control rate was improved in arm B (66%; 95% CI = 51%-78%) ve rsus arm A (42%; 95% CI = 31%-56%), Conclusion: The statistically significa nt improvement in overall survival that was obtained supports the use of co ncomitant chemotherapy as an adjunct to radiotherapy in the management of c arcinoma of the oropharynx.