Customized Adjuvant Chemotherapy Based on Biomarker Examination May Improve Survival of Patients Completely Resected for Non-small-cell Lung Cancer.

Abstract

AIM:

Adjuvant platinum-based chemotherapy is recommended for patients with completely resected stage II (N1) or III (N2) non-small cell lung cancer (NSCLC). However, the optimal chemotherapy regimen is difficult to predict for individual patients. Our previous prospective study on individualized treatment according to biomarker status, such as excision repair cross-complementing 1 (ERCC1), class III β-tubulin (tubulin), thymidylate synthase (TYMS) and ribonucleotide reductase M1 (RRM1), achieved encouraging results in patients with advanced NSCLC. The present study further examined the effect of biomarker-based adjuvant chemotherapy in patients with completely resected NSCLC.

PATIENTS AND METHODS:

Between January 2006 and December 2014, 66 patients with localized (stage I-IIIA) NSCLC who underwent R0 operation received 2-4 cycles of platinum doublet adjuvant chemotherapy: Platinum plus docetaxel, platinum plus pemetrexed for adenocarcinoma, and platinum plus tegafur/gimeracil/oteracil combination (TS-1) for squamous cell carcinoma (SCC) were selected according to the registered protocol at each period. Immunohistochemistry was used to evaluate the biomarkers: ERCC1 status for platinum, tubulin for docetaxel, and TYMS for pemetrexed and TS-1. A matched chemotherapy regimen meant that platinum plus docetaxel was administered in patients negative for ERCC1 and negative for tubulin, platinum plus pemetrexed in patients with adenocarcinoma positive for tubulin, negative for ERCC1 and negative for TYMS, and platinum plus TS-1 in those with SCC positive for tubulin, negative for ERCC1 and negative for TYMS.

RESULTS:

The 5-year survival rate was 77.5% considering all 66 patients, and 85.7%, 71.8%, and 78.8% for those with p-stage I, II, and III, respectively. Patients who received a matched chemotherapy regimen (n=13; platinum plus docetaxel in eight, platinum plus pemetrexed in five) had significantly better 5-year survival than patients with unmatched biomarker status (n=53) (100% vs. 71.0%, p=0.0011).

CONCLUSION:

Customized adjuvant chemotherapy based on biomarker examination significantly improved the survival of patients with NSCLC, regardless of p-stage.

• Authors: Dage Liu, Nariyasu Nakashima, Jun Nakano, Shintaro Tarumi, Natsumi Matsuura, Takayuki Nakano, Kazuhito Nii, Yoshimasa Tokunaga, Tetsuhiko Go, Hiroyasu Yokomise
• Journal: Anticancer research (Anticancer Res) Vol. 37 Issue 5 Pg. 2501-2507 (05 2017) ISSN: 1791-7530 [Electronic] Greece
• PMID: 28476819 (Publication Type: Journal Article)
• Copyright: Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Chemical References

• Antineoplastic Agents
• Biomarkers, Tumor
• DNA-Binding Proteins
• Drug Combinations
• Pyridines
• Taxoids
• Tubulin
• Tumor Suppressor Proteins
• tegafur-gimeracil-oteracil
• Pemetrexed
• Tegafur
• Docetaxel
• Oxonic Acid
• Carboplatin
• RRM1 protein, human
• Ribonucleoside Diphosphate Reductase
• TYMS protein, human
• Thymidylate Synthase
• ERCC1 protein, human
• Endonucleases

Topics

• Adult
• Aged
• Antineoplastic Agents (therapeutic use)
• Biomarkers, Tumor (metabolism)
• Carboplatin (therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism, surgery)
• Chemotherapy, Adjuvant
• DNA-Binding Proteins (metabolism)
• Disease-Free Survival
• Docetaxel
• Drug Combinations
• Endonucleases (metabolism)
• Female
• Humans
• Lung Neoplasms (drug therapy, metabolism, surgery)
• Male
• Middle Aged
• Oxonic Acid (therapeutic use)
• Pemetrexed (therapeutic use)
• Pyridines (therapeutic use)
• Ribonucleoside Diphosphate Reductase
• Taxoids (therapeutic use)
• Tegafur (therapeutic use)
• Thymidylate Synthase (metabolism)
• Tubulin (metabolism)
• Tumor Suppressor Proteins (metabolism)