Document Detail


A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker.
MedLine Citation:
PMID:  23338051     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
PURPOSE: The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer.
METHODS: Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry.
RESULTS: A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4%, and disease control ratio was 100%. Grade 4 neutropenia developed in 53.5% of patients and febrile neutropenia in 16.3%. Non-hematological grade 3/4 adverse events were anorexia (23.3%), nausea (14.0%), and diarrhea (23.3%), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7%, and a pathological response was found in 65.9% of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5%.
CONCLUSIONS: Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.
Authors:
Masahiro Hirakawa; Yasushi Sato; Hiroyuki Ohnuma; Tetsuji Takayama; Tamotsu Sagawa; Takayuki Nobuoka; Keisuke Harada; Hiroshi Miyamoto; Yasuhiro Sato; Yasuo Takahashi; Shinich Katsuki; Michiaki Hirayama; Minoru Takahashi; Michihiro Ono; Masahiro Maeda; Kohichi Takada; Tsuyoshi Hayashi; Tsutomu Sato; Koji Miyanishi; Rishu Takimoto; Masayoshi Kobune; Koichi Hirata; Junji Kato
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study     Date:  2013-01-22
Journal Detail:
Title:  Cancer chemotherapy and pharmacology     Volume:  71     ISSN:  1432-0843     ISO Abbreviation:  Cancer Chemother. Pharmacol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-04-08     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  7806519     Medline TA:  Cancer Chemother Pharmacol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  789-97     Citation Subset:  IM    
Affiliation:
Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Antimetabolites, Antineoplastic / administration & dosage
Antineoplastic Agents / administration & dosage
Antineoplastic Agents, Phytogenic / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Biological Markers
Cisplatin / administration & dosage
Combined Modality Therapy
DNA Repair / drug effects
DNA-Binding Proteins / genetics,  metabolism
Drug Administration Schedule
Drug Combinations
Drug Resistance, Neoplasm / genetics
Endonucleases / genetics,  metabolism
Endosonography
Female
Follow-Up Studies
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Neoadjuvant Therapy / methods*
Oxonic Acid / administration & dosage
Stomach Neoplasms / drug therapy*,  surgery*
Survival Analysis
Taxoids / administration & dosage
Tegafur / administration & dosage
Tomography, X-Ray Computed
Treatment Outcome
Chemical
Reg. No./Substance:
0/Antimetabolites, Antineoplastic; 0/Antineoplastic Agents; 0/Antineoplastic Agents, Phytogenic; 0/Biological Markers; 0/DDB2 protein, human; 0/DNA-Binding Proteins; 0/Drug Combinations; 0/Taxoids; 150863-82-4/S 1 (combination); 15663-27-1/Cisplatin; 15H5577CQD/docetaxel; 17902-23-7/Tegafur; 937-13-3/Oxonic Acid; EC 3.1.-/ERCC1 protein, human; EC 3.1.-/Endonucleases

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