Evidence-based recommendations against neoadjuvant chemotherapy for routine management of patients with squamous cell head and neck cancer.

The objective of this study was to determine appropriate recommendations for neoadjuvant chemotherapy in the treatment of head and neck cancer (HNC). Published reports of randomized trials of neoadjuvant versus standard therapy in patients with stage III and stage IV HNC were identified by literature search. The overall trial results were analyzed using three pooling techniques: vote count, weighted median survival, and meta-analysis of published survival data. Excluded from analysis were articles on intra-arterial therapy, studies without a standard treatment control arm, studies that included adjuvant therapy, and abstracts. Twelve studies were evaluable for vote count, 11 for weighted median survival analysis, and 10 for quantitative meta-analysis. By vote count there was no observed survival difference in 7 trials, a trend favoring control in 3, a statistically significant difference favoring control in 1, and a trend favoring neoadjuvant therapy in 1. The weighted median survival was 20.9 months for control versus 20.0 months for neoadjuvant chemotherapy, with consistent trends for resectable and nonresectable disease and for chemotherapy combinations versus single agents. The common odds ratios for deaths at 12, 24, and 36 months were 1.12, 1.27, and 1.11, respectively, all in favor of control treatment. Data generated using rigorous methodological standards indicate that neoadjuvant chemotherapy should not be offered to patients with locally advanced HNC if improved survival is the outcome of interest. It is premature to recommend neoadjuvant chemotherapy to preserve organ function, although patients should be aware of this option and the limitations of the current data.