Cetuximab, Fluorouracil, and Cisplatin, with/without Docetaxel, in Recurrent or Metastatic Head and Neck Cancer
The AIO 1108 study was an open-label, randomized, multicenter trial that evaluated the efficacy and tolerability of cetuximab, fluorouracil, cisplatin (PFC) plus docetaxel (PFCD) versus a standard PFC regimen in patients with recurrent or metastatic head and neck squamous-cell carcinoma (SCC). The final analysis of this trial was reported at the 2014 ESMO meeting (Knoedler M, et al. AIO trial 1108. ESMO 2014: Abstract 987O).
In this trial, 180 patients were randomized to receive either the PFCD regimen (cisplatin 40 mg/m2, docetaxel 40 mg/m2, and fluorouracil 2000 mg/m2 on days 1 and 8, and cetuximab 400/250 mg/m2 on days 1, 8, and 15 every 3 weeks), or PFC (cisplatin 100 mg/m2 on day 1, fluorouracil 1000 mg/m2 on days 1 to 4, and cetuximab 400/250 mg/m2 on days 1, 8, and 15 every 3 weeks) for 6 cycles, followed by cetuximab maintenance (500 mg/m2 every 2 weeks). Because of excessive toxicities in the experimental arm, cisplatin was reduced to 30 mg/m2 and fluorouracil was reduced to 1000 mg/m2 after the enrollment of 20 patients in each arm.
At a median follow-up of 2 years, the toxicity rates were similar in both arms. The incidences of grade 4 toxicities were 21.3% in the PFCD arm and 30.8% in the standard arm. Potential treatment-related deaths occurred in 11.2% in the PFCD arm and 6.6% in the standard arm. There were no significant improvements in median progression-free survival (5.4 vs 5 months; hazard ratio [HR], 0.79; P = .375) and overall survival (9.8 vs 9.7 months; HR, 1.39; P = .993). The response rates were numerically higher in the 4-drug combination (38.2% vs 31.9%), but were not statistically significant.
Overall, these results indicate that the 4-drug regimen was not associated with improved survival outcomes and did not support the addition of docetaxel to the standard regimen in patients with recurrent or metastatic head and neck SCC.