Class III beta-tubulin expression and benefit from adjuvant cisplatin/vinorelbine chemotherapy in operable non-small cell lung cancer: analysis of NCIC JBR.10.
OBJECTIVE
High class III beta-tubulin (bTubIII) expression in advanced non-small cell lung cancer is known to correlate with reduced response rates and inferior survival with anti-microtubule agents. JBR.10 showed a 12% and 15% improvement in 5-year recurrence-free survival (RFS) and overall survival (OS), respectively, with the addition of cisplatin and vinorelbine following resection of stage IB-II non-small cell lung cancer. We sought to determine the effect of bTubIII on patient outcome and benefit from adjuvant chemotherapy in the JBR.10 trial.


METHODS
We did a semiquantitative immunohistochemical assay for bTubIII on primary tumor tissue available from 265 of the 482 patients in JBR.10. Tumors were classified as bTubIII "low" or "high" using a validated method. We examined the prognostic effect of bTubIII in patients treated with or without chemotherapy and the survival benefit from chemotherapy in low versus high bTubIII subgroups.


RESULTS
High bTubIII expression was associated with poorer RFS and OS in patients treated with surgery alone but not in patients treated with adjuvant chemotherapy. The RFS and OS benefits of adjuvant chemotherapy were greater in high versus low tubulin expressors. However, with Cox regression, the interaction between bTubIII status and chemotherapy treatment in predicting RFS or OS did not reach statistical significance.


CONCLUSIONS
Chemotherapy seemed to overcome the negative prognostic effect of high bTubIII expression. Greater benefit from adjuvant chemotherapy was seen in patients with high bTubIII expression. This is contrary to what has been seen in the setting of advanced disease; possible reasons for this difference are being explored.
Sève
Pascal
P
Cross Cancer Institute, University of Alberta, Edmonton, Alberta, Canada.
Lai
Raymond
R
Ding
Keyue
K
Winton
Timothy
T
Butts
Charles
C
Mackey
John
J
Dumontet
Charles
C
Dabbagh
Laith
L
Aviel-Ronen
Sarit
S
Seymour
Lesley
L
Whitehead
Marlo
M
Tsao
Ming-Sound
MS
Shepherd
Frances A
FA
Reiman
Tony
T
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D017024:Chemotherapy, Adjuvant; D002945:Cisplatin / Q000008:administration & dosage*; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013997:Time Factors; D016896:Treatment Outcome; D014404:Tubulin / Q000096:biosynthesis*; D014747:Vinblastine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000077235:Vinorelbine
C498585:TUBB3 protein, human; D014404:Tubulin; D014747:Vinblastine; D002945:Cisplatin; D000077235:Vinorelbine