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
ABSTRACT 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.
- [Show abstract] [Hide abstract]
ABSTRACT: Neoadjuvant chemotherapy for locally advanced gastric cancer leads to major histopathological response in less than 30 % of patients. Data on interim endoscopic response assessment do not exist. This exploratory prospective study evaluates early endoscopy after 50 % of the chemotherapy as predictor for later response and prognosis. Forty-seven consecutive patients were included (45 resected; 33 R0 resections). All patients received baseline endoscopy and CT scans, after 50 % of their chemotherapy (EGD-1, CT-1) and after completion of chemotherapy (EGD-2, CT-2). Interim endoscopic response (EGD-1) was assessed after having received 50 % (6 weeks) of the planned 12 weeks of neoadjuvant chemotherapy. Post-chemotherapy response was clinically assessed by a combination of CT scan (CT-2) and endoscopy (EGD-2). Histopathological response was determined by a standardized scoring system (Becker criteria). Endoscopic response was defined as a reduction of >75 % of the tumor mass. Twelve patients were responders at EGD-1 and 13 at EGD-2. Nine patients (19.1 %) were clinical responders and 7 patients (15.6 %) were histopathological responders after chemotherapy. Specificity, accuracy, and negative predictive value of the interim EGD-1 for subsequent histopathological response were 31/38 (82 %), 36/47 (76 %), and 31/33 (93 %); and for recurrence or death, 28/30 (93.3 %), 38/47 (80.9 %), and 28/35 (80.0 %). Response at EGD-1 was significantly associated with histopathological response (p = 0.010), survival (p < 0.001), and recurrence-free survival (p = 0.009). Interim endoscopy after 6 weeks predicts response and prognosis. Therefore, tailoring treatment according to interim endoscopic assessment could be feasible, but the findings of this study should be validated in a larger patient cohort.Gastric Cancer 09/2013; DOI:10.1007/s10120-013-0296-0 · 4.83 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The aim of the study reported here was to identify whether a stem cell biomarker, Lin28, may predict the pathologic tumor response to neoadjuvant chemotherapy for patients with locally advanced gastric cancer. The study enrolled 47 patients with gastric cancer who underwent neoadjuvant chemotherapy followed by surgery between July 2004 and March 2012. Cancer tissue was biopsied by gastroscopy and Lin28 expression in the tissue was measured by immunohistochemistry. Statistical analyses were performed to identify the relationship between Lin28 expression and tumor regression grade. Of the 47 cases, pathologic nonresponse was observed in 29 (61.7%) and pathologic response in 18 (38.3%). Receiver-operating characteristic curve analysis showed that the histoscore of Lin28 expression with 0.325 as a cutoff value could differentiate between pathologic response and nonresponse. Multivariable analysis showed that Lin28 expression was an independent predictive factor for pathologic response to neoadjuvant chemotherapy (P = 0.006). Lin28 expression was associated with pathologic tumor response in locally advanced gastric cancer patients undergoing neoadjuvant chemotherapy. This may suggest that Lin28 can serve as a predictive biomarker for neoadjuvant chemotherapy in patients with gastric cancer.OncoTargets and Therapy 09/2013; 6:1341-1345. DOI:10.2147/OTT.S45705 · 2.31 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: The combination of docetaxel and S-1 (DS) therapy is effective in patients with unrespectable gastric cancer and is expected to be a regimen in neoadjuvant setting for advanced gastric cancer. This study was held to evaluate the efficacy and safety of DS followed by surgery. Patients with resectable gastric cancer received 2 courses of docetaxel 40 mg/m(2) on days 1, 15 and S-1 40 mg/m(2) bid orally on days 1-7, 15-21 every 4 weeks, followed by standard radical gastrectomy. Primary end point was the pathological response rate: rate of tumors in which one-third or more parts were affected. Fourteen patients were enrolled. Thirteen (92.8 %) patients completed two courses of chemotherapy. Grade 3 adverse events were neutropenia in 3 (21.4 %) patients, anemia in 1 (6.2 %) patient and diarrhea in 1 (6.2 %) patient. There were no grade 4 adverse event and febrile neutropenia. All patients underwent R0 resection, and pathological response was found in 50.0 % of patients. There were no major surgical complications and no treatment-related mortality. The neoadjuvant chemotherapy with DS was effective for patients with locally advanced gastric cancer with manageable toxicities. Further study to confirm the usefulness of this regimen is needed.Cancer Chemotherapy and Pharmacology 11/2013; DOI:10.1007/s00280-013-2350-3 · 2.57 Impact Factor