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

• Published in: Cancer chemotherapy and pharmacology 2013-03, Vol.71 (3), p.789-797
• Main Authors: Hirakawa, Masahiro, Sato, Yasushi, Ohnuma, Hiroyuki, Takayama, Tetsuji, Sagawa, Tamotsu, Nobuoka, Takayuki, Harada, Keisuke, Miyamoto, Hiroshi, Sato, Yasuhiro, Takahashi, Yasuo, Katsuki, Shinich, Hirayama, Michiaki, Takahashi, Minoru, Ono, Michihiro, Maeda, Masahiro, Takada, Kohichi, Hayashi, Tsuyoshi, Sato, Tsutomu, Miyanishi, Koji, Takimoto, Rishu, Kobune, Masayoshi, Hirata, Koichi, Kato, Junji
• Format: Article
• Language: English
• Subjects: Adult; Aged; anorexia; Antimetabolites, Antineoplastic - administration & dosage; Antineoplastic agents; Antineoplastic Agents - administration & dosage; Antineoplastic Agents, Phytogenic - administration & dosage; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Biological and medical sciences; Biomarkers; Cancer Research; Chemoresistance; Chemotherapy; Cisplatin; Cisplatin - administration & dosage; Combined Modality Therapy; Dendritic cells; Diarrhea; Disease control; DNA damage; DNA Repair - drug effects; DNA-binding protein; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Drug Administration Schedule; Drug Combinations; Drug Resistance, Neoplasm - genetics; Endonucleases - genetics; Endonucleases - metabolism; Endosonography; ERCC1 protein; Female; Follow-Up Studies; Gastric cancer; Gastroenterology. Liver. Pancreas. Abdomen; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Medical sciences; Medicine; Medicine & Public Health; Middle Aged; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Nausea; Neoadjuvant Therapy - methods; Neutropenia; Nucleotide excision repair; Oncology; Original Article; Oxonic Acid - administration & dosage; Pharmacology. Drug treatments; Pharmacology/Toxicology; Stomach Neoplasms - drug therapy; Stomach Neoplasms - surgery; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Surgery; Survival Analysis; Taxoids - administration & dosage; Tegafur - administration & dosage; Tomography, X-Ray Computed; Toxicity; Treatment Outcome; Tumors
• ISSN: 0344-5704; 1432-0843
• DOI: 10.1007/s00280-013-2073-5

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.