Randomised phase-III-trial of concurrent chemoradiation (CRT) for locally advanced head and neck cancer (stage III-IVB): Comparing dose reduced radiotherapy (63,6 Gy) with paclitaxel/cisplatinum to standard radiotherapy (70,6 Gy) with fluorouracil/cisplatinum.

6016 Background: Concurrent CRT with 70.6 Gy is the standard treatment for locally advanced head and neck cancer (LA-SCCHN). There exist no prospective data on safety and efficacy of a reduced radiation (RT) dose. Methods: Pts with stage III-IVB LA-SCCHN were randomized 1:1 to receive 70.6 Gy with concurrent cisplatinum (20mg/m²/d IV on days 1-5 and 29-33) and fluorouracil (600 mg/m²/d CIV on days 1-5 and 29-33) (standard arm A) versus 63,6 Gy with intensified chemotherapy using concurrent cisplatinum (20mg/m²/d IV on days 1-4 and 29-32) and paclitaxel (20mg/m²/d IV on days 2, 5, 8, 11 and 25, 30, 33, 36) (experimental arm B). After a planned interim analysis recruitment was stopped due to statistical reasons. Results: Between 06/2010 and 02/2015 a total of 221 pts were randomized with 105 pts receiving treatment in arm A and 112 in arm B (4 pts dropped out). Median follow-up was 38 months. Pts’ characteristics: Oral cavity (15%), oropharynx (54%), hypopharynx (28%), larynx (14%); 17 pts had more than one primary site; tumor stage: III (14%), IV (86%); HPV-status (p16) was positive in 20%, negative in 38%, currently pending in 42%. A total of 96 PFS-related events occurred. 3-year PFS (ITT) was 58% in the standard arm A and 48% in experimental arm B (p = 0.454). 3-year OS (ITT) was 64% in arm A and 59% in arm B (p = 0.688). 3-year rates of distant metastases, loco-regional recurrences and death were 10% vs 12%, 17% vs 21% and 15% vs 19% for pts in arm A and B, respectively. As for the p16-positive subgroup, 3-year PFS/OS were 77%/76% in arm A (n = 21) and 69%/80% in arm B (n = 22), respectively. Grade 3+ hematologic adverse events during therapy (arm A/arm B): Anemia 11%/4% (p = 0.038); neutropenia 40%/16% (p < 0.001); thrombocytopenia 8%/3% (p = 0.130). Conclusions: These preliminary results indicate that pts receiving concurrent CRT for LA-SCCHN did not benefit from a lower total RT dose of 63.6Gy despite intensified chemotherapy. However, in the subgroup of p16-positive pts a reduced RT dose may be sufficiently effective. Clinical trial information: NCT01126216.