Retrospective analysis of second-line chemotherapy outcomes with paclitaxel or docetaxel in correlation with STMN1 polymorphism in advanced non-small cell lung cancer patients

• Published in: Clinical & translational oncology 2016-01, Vol.18 (1), p.33-39
• Main Authors: Powrózek, T., Mlak, R., Krawczyk, P., Bartoń, S., Biernacka, B., Małecka-Massalska, T., Milanowski, J.
• Format: Article
• Language: English
• Subjects: Aged; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Carcinoma, Non-Small-Cell Lung - drug therapy; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - pathology; Chemotherapy, Adjuvant; Disease Progression; Female; Humans; Lung Neoplasms - drug therapy; Lung Neoplasms - genetics; Lung Neoplasms - mortality; Lung Neoplasms - pathology; Male; Medicine; Medicine & Public Health; Middle Aged; Oncology; Paclitaxel - therapeutic use; Polymorphism, Single Nucleotide; Research Article; Retrospective Studies; Stathmin - genetics; Taxoids - administration & dosage; Taxoids - therapeutic use; Treatment Outcome
• ISSN: 1699-048X; 1699-3055
• DOI: 10.1007/s12094-015-1333-8

Purpose Second-line chemotherapy of advanced non-small cell lung cancer (NSCLC) with docetaxel or pemetrexed allows to achieve objective response rate only in 5–10 % of patients. Recent studies have shown that single nucleotide polymorphisms (SNPs) in genes encoding proteins which regulate dynamics of microtubules may be considered as predictive factors of response to taxane-based chemotherapy. STMN1 gene encodes stathmin 1, which plays role in cell division by regulation of microtubules depolarisation, and this process may be associated with taxanes’ effectiveness. Materials and methods Using HRM-PCR technique, we evaluated the −2166C>T SNP of STMN1 gene in DNA from peripheral blood leucocytes of 54 advanced NSCLC patients treated in second-line monotherapy with docetaxel or paclitaxel. Results Patients with TT genotype of STMN1 gene demonstrated significantly longer progression-free survival (PFS) and the lower risk of early disease progression after second-line treatment compared to patients with other STMN1 genotypes (median PFS: 7 and 2 months; p  = 0.0154; HR = 0.371; 95 % CI 0.184–0.743). Early disease progression during second-line chemotherapy was significantly more frequently observed in patients with CC genotype of STMN1 in contrast to patients with presence of T allele (median PFS: 2 and 4 months; p  = 0.0385; HR = 1.776; 95 % CI 0.905–3.445). Conclusion Only selected NSCLC patients could benefit from second-line chemotherapy. Therefore, investigations of novel predictive molecular factors for proper qualification of patients to second-line taxane-based chemotherapy are justified. Studied SNP of STMN1 gene may have potential predictive role in such therapy.