Long-term results of conventional radiotherapy versus accelerated hyperfractionated radiotherapy versus concomitant radiotherapy and chemotherapy in locoregionally advanced carcinoma of the oropharynx

• Published in: Tumori 2006-01, Vol.92 (1), p.41-54
• Main Authors: Fallai, Carlo, Bolner, Andrea, Signor, Marco, Gava, Alessandro, Franchin, Giovanni, Ponticelli, Pietro, Taino, Raffaella, Rossi, Francesca, Ardizzoia, Alessandro, Oggionni, Maria, Crispino, Sergio, Olmi, Patrizia
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biomarkers, Tumor - analysis; Carboplatin - administration & dosage; Carcinoma, Squamous Cell - drug therapy; Carcinoma, Squamous Cell - pathology; Carcinoma, Squamous Cell - radiotherapy; Chemotherapy, Adjuvant - adverse effects; Dose Fractionation; Female; Fluorouracil - administration & dosage; Humans; Male; Middle Aged; Neoplasm Staging; Neoplasms, Second Primary - drug therapy; Neoplasms, Second Primary - radiotherapy; Oropharyngeal Neoplasms - drug therapy; Oropharyngeal Neoplasms - pathology; Oropharyngeal Neoplasms - radiotherapy; Radiotherapy, Adjuvant - adverse effects; Radiotherapy, Adjuvant - methods; Risk Factors; Salvage Therapy; Survival Analysis; Time Factors; Treatment Failure; Treatment Outcome
• ISSN: 0300-8916; 2038-2529
• DOI: 10.1177/030089160609200108

To compare conventional fractionation (CF) radiation therapy (RT), arm A, versus a split-course accelerated hyperfractionated schedule (S-AHF), arm B, versus CFRT plus concomitant chemotherapy (CT), arm C, in terms of five-year survival and toxicity for squamous cell tumors of the oropharynx. Between January 1993 and June 1998, 192 previously untreated patients with stage III and IV oropharyngeal carcinoma (excluding T1N1 and T2N1) were enrolled in a multicenter randomized phase III trial (ORO 93-01). In arms A and C, 66 to 70 Gy in 33 to 35 fractions was administered five days a week for six and a half to seven weeks. In arm B, the dose delivered was 64 to 67.2 Gy in two fractions of 1.6 Gy every day, five days a week, with a planned two-week split at 38.4 Gy. In arm C the CT regimen consisted of three cycles of carboplatin and 5-fluorouracil (CBDCA 75 mg/m2 on days 1 to 4 and 5-FU 1000 mg/m2 i.v. on days 1 to 4 every 28 days). No statistically significant difference was found in five-year overall survival (P = 0.39): 21% for arm A, 21% for arm B, and 40% for arm C. Similarly, there was no statistically significant difference in terms of five-year relapse-free survival: 15% for arm A, 17% for arm B, and 36% for arm C. There was a slight trend towards better five-year locoregional control (P = 0.07) for the combined arm: patients without locoregional relapse were 48% in arm C, 21% in arm A and 18% in arm B. Locoregional control was significantly better when arm C was compared with arms A and B combined (P = 0.02; arm A+B 20%; arm C 48%). Distant metastases were fairly balanced in the three arms (A: 14; B: 9; C: 11), with a tendency towards more frequent isolated distant metastasis development in arm C (8 of 11 [72%] versus 7 of 23 [30%] in arms A+B). Five-year second-tumor-free survival was 85%. The 13 second tumors were equally distributed and were mainly correlated with tobacco and alcohol consumption (five lung, two esophagus, two oral cavity, one larynx, one pancreas, one hepatocarcinoma, one myeloma). Arm C showed slightly more G3+ late side effects involving subcutaneous tissues and mucosa, although significant late sequelae were relatively uncommon and the mucosal side effects were mostly transient. The occurrence of persistent G3 xerostomia was comparable in the three treatment arms. The results obtained with the combination of CT and RT compared with RT alone did not reach statistical significance, but combined treatment almost doubled the five-ye