beta-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.
OBJECTIVE
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 [betaT-2], and HER2 neu) was evaluated by immunohistochemistry.


RESULTS
For patients with low betaT-II expression, median overall survival (OS) was 58.6 months (95% CI, not reached [NR]), compared with 18.2 months for patients with high betaT-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 betaT-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 betaT-II expression, with a HR of 1.9 (95% CI, 1.43 to 2.77; P < .0001). The predictive value of betaT-II expression was greater in the TPF versus PF arm than in the PF arm.


CONCLUSIONS
Increased tumor expression of betaT-II is strongly associated with adverse outcome in LASCCHN patients treated with IC, and our data suggest low expression of betaT-II may predict patients most likely to benefit from induction TPF therapy. Further, simple models which combine expression of betaT-II with a carefully defined set of additional immunohistochemical markers may have significant prognostic impact for patients with LASCCHN.
Cullen
Kevin J
KJ
University of Maryland Marlene and Stewart Greenebaum Cancer Center, 22 S. Greene St, Room N9E17, Baltimore, MD 21201, USA. kcullen@umm.edu
Schumaker
Lisa
L
Nikitakis
Nikolaos
N
Goloubeva
Olga
O
Tan
Ming
M
Sarlis
Nicholas J
NJ
Haddad
Robert I
RI
Posner
Marshall R
MR
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000096:biosynthesis; D016190:Carboplatin / Q000008:administration & dosage; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D000077143:Docetaxel; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism* / Q000532:radiotherapy; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D043823:Taxoids / Q000008:administration & dosage; D016896:Treatment Outcome; D014404:Tubulin / Q000096:biosynthesis*
D014408:Biomarkers, Tumor; D043823:Taxoids; D014404:Tubulin; D000077143:Docetaxel; D016190:Carboplatin; D002945:Cisplatin; D005472:Fluorouracil