β-Tubulin-II Expression Strongly Predicts Outcome in Patients Receiving Induction Chemotherapy for Locally Advanced Squamous Carcinoma of the Head and Neck: A Companion Analysis of the TAX 324 Trial

Purpose TAX 324 was a phase III trial comparing induction chemotherapy (IC) with docetaxel, cisplatin, and fluorouracil (TPF) with cisplatin and fluorouracil (PF) followed by concomitant chemoradiotherapy in locally advanced squamous cell cancer of the head and neck (LASCCHN). This study evaluates a series of tumor markers in pretreatment biopsies from that trial TAX 324 and correlates expression with survival. Methods Pretherapy biopsy specimens were available for 265 of 501 participants. Expression of a series of six markers (p53, thymidylate synthase, glutathione s-transferase pi [GST-pi], Bcl 2, beta tubulin II [beta T-2], and HER2 neu) was evaluated by immunohistochemistry. Results For patients with low beta T-II expression, median overall survival (OS) was 58.6 months (95% CI, not reached [NR]), compared with 18.2 months for patients with high beta T-II expression (95% CI, 13.11 to 30.06: hazard ratio [HR], 2.39; 95% CI, 1.67 to 3.72; P < .0001). Progression-free survival in patients with low beta T-II expression was 43.2 months (95% CI, 24.4 to NR) versus 9.8 months (95% CI, 7.06 to 18.53) for high beta T-II expression, with a HR of 1.9 (95% CI, 1.43 to 2.77; P < .0001). The predictive value of beta T-II expression was greater in the TPF versus PF arm than in the PF arm. Conclusion Increased tumor expression of beta T-II is strongly associated with adverse outcome in LASCCHN patients treated with IC, and our data suggest low expression of beta T-II may predict patients most likely to benefit from induction TPF therapy. Further, simple models which combine expression of beta T-II with a carefully defined set of additional immunohistochemical markers may have significant prognostic impact for patients with LASCCHN.