Conversion therapy for inoperable advanced gastric cancer patients by docetaxel, cisplatin, and S-1 (DCS) chemotherapy: a multi-institutional retrospective study.

BACKGROUND: Conversion therapy is an option for unresectable metastatic gastric cancer when distant metastases are controlled by chemotherapy; however, the feasibility and efficacy remain unclear. This study aimed to assess the feasibility and efficacy of conversion therapy in patients with initially unresectable gastric cancer treated with docetaxel, cisplatin, and S-1 (DCS) chemotherapy by evaluating clinical outcomes. METHODS: One hundred unresectable metastatic gastric cancer patients, enrolled in three DCS chemotherapy clinical trials, were retrospectively evaluated. The patients received oral S-1 (40 mg/m2 b.i.d.) on days 1-14 and intravenous cisplatin (60 mg/m2) and docetaxel (50-60 mg/m2) on day 8 every 3 weeks. Conversion therapy was defined when the patients could undergo R0 resection post-DCS chemotherapy and were able to tolerate curative surgery. RESULTS: Conversion therapy was achieved in 33/100 patients, with no perioperative mortality. Twenty-eight of the 33 patients (84.8 %) achieved R0 resection, and 78.8 % were defined as histological chemotherapeutic responders. The median overall survival (OS) of patients who underwent conversion therapy was 47.8 months (95 % CI 28.0-88.5 months). Patients who underwent R0 resection had significantly longer OS than those who underwent R1 and R2 resections (P = 0.0002). Of the patients with primarily unresectable metastases, 10 % lived >5 years. Among patients who underwent conversion therapy, multivariate analysis showed that the pathological response was a significant independent predictor for OS. CONCLUSIONS: DCS safely induced a high conversion rate, with very high R0 and pathological response rates, and was associated with a good prognosis; these findings warrant further prospective investigations.

Trastuzumab in combination with docetaxel/cisplatin/S-1 (DCS) for patients with HER2-positive metastatic gastric cancer: feasibility and preliminary efficacy.

PURPOSE: We previously reported that a triplet combination of docetaxel, cisplatin, and S-1 (DCS) is active against metastatic gastric cancer with a very high response rate of 87.1 % in a phase II study. Recently, the efficacy of trastuzumab (T-mab) for the treatment of HER2-positive gastric cancer has been reported. Therefore, we investigated the feasibility and preliminary efficacy of DCS + T-mab (DCS-T) for unresectable HER2-positive metastatic gastric cancer. METHODS: Patients received oral S-1 (40 mg/m(2) b.i.d.) on days 1-14, intravenous cisplatin (60 mg/m(2)), docetaxel (50 mg/m(2)), and T-mab (8 mg/kg in the first cycle and 6 mg/kg in the second cycle and thereafter) on day 8 every 3 weeks. RESULTS: The study included 16 patients: median age, 60 (34-76) years; males/females, 11:5; intestinal-type/diffuse-type histology, 11:5; and HER2 3+/2+(FISH+), 13:3. The completion rate until the third cycle was 87.5 % (14/16) (95 %CI 71.3-103.7 %). Adverse events of grade 3/4 severity during the first 3 cycles were: leukopenia/neutropenia, 50.0:75.0 %; febrile neutropenia, 12.5 %; diarrhea, 12.5 %; and stomatitis, 12.5 %. All of these side effects were manageable and well controlled. There were no treatment-related deaths. The overall response rate was 93.8 % (15/16), and the response rate in patients with measurable lesions was 100 % (15/15). The median cycle to response was only 1 (1-3 cycles). Non-curative factors disappeared in 56.3 % (9/16) of patients, and conversion surgery (R0 resection) was performed in all these cases. Pathological response rates in primary and metastatic lesions were 88.9 % (8/9) and 100 % (9/9), respectively. The median PFS and OS were not reached during the median follow-up time of 18.3 months ranged from 11.0 to 34.3 months. CONCLUSIONS: DCS-T was feasible in patients with unresectable HER2-positive metastatic gastric cancer. The observed response was very promising and warrants further investigation. CLINICAL TRIAL REGISTRATION NUMBER: UMIN000005603.

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.

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.