|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.|
|PMID: 23338051 Owner: NLM Status: MEDLINE|
|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.
|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|
|Type: Clinical Trial, Phase II; Journal Article; Multicenter Study Date: 2013-01-22|
|Title: Cancer chemotherapy and pharmacology Volume: 71 ISSN: 1432-0843 ISO Abbreviation: Cancer Chemother. Pharmacol. Publication Date: 2013 Mar|
|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|
|Languages: eng Pagination: 789-97 Citation Subset: IM|
|Fourth Department of Internal Medicine, Sapporo Medical University School of Medicine, South 1 West 16, Chuo-ku, Sapporo 060-8543, Japan.|
|APA/MLA Format Download EndNote Download BibTex|
Antimetabolites, Antineoplastic / administration & dosage
Antineoplastic Agents / administration & dosage
Antineoplastic Agents, Phytogenic / administration & dosage
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Cisplatin / administration & dosage
Combined Modality Therapy
DNA Repair / drug effects
DNA-Binding Proteins / genetics, metabolism
Drug Administration Schedule
Drug Resistance, Neoplasm / genetics
Endonucleases / genetics, metabolism
Neoadjuvant Therapy / methods*
Oxonic Acid / administration & dosage
Stomach Neoplasms / drug therapy*, surgery*
Taxoids / administration & dosage
Tegafur / administration & dosage
Tomography, X-Ray Computed
|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|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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