Phase II study of laparoscopy-assisted distal gastrectomy with nodal dissection for clinical stage I gastric cancer: Japan Clinical Oncology Group Study JCOG0703

A phase II trial was started in Japan to evaluate the safety of laparoscopy-assisted distal gastrectomy (LADG) for clinical stage I gastric cancer. A total of 170 patients will be enrolled in this study by expert surgeons for laparoscopy from 16 institutions over 1 year. The primary endpoint is incidence of anastomotic leak and pancreatic fistula. The secondary endpoints are overall survival, relapse-free survival, proportion of completion of LADG, proportion of conversion from LADG to open gastrectomy, surgical morbidity and short-term clinical outcomes.     

A phase II study of biweekly mitomycin C and irinotecan combination therapy in patients with fluoropyrimidine-resistant advanced gastric cancer: a report from the Gastrointestinal Oncology Group of the Japan Clinical Oncology Group (JCOG0109-DI Trial)

Background

Preclinical studies have shown that mitomycin C (MMC) acts synergistically with irinotecan (CPT-11). In this phase II study, we evaluated the efficacy and toxicity of MMC/CPT-11 therapy as second-line chemotherapy for patients with fluoropyrimidine-resistant advanced gastric cancer.

Methods

Eligible patients had evidence of tumor progression despite prior treatment with fluoropyrimidine-based regimens or had relapsed within 6?months after completion of therapy with adjuvant fluoropyrimidines. Treatment consisted of MMC (5?mg/m²) and CPT-11 (150?mg/m²) administered i.v. every 2?weeks. The primary endpoint was the response rate (RR). Our hypothesis was that this combination therapy was efficacious when the lower boundary of the 95% confidence interval (CI) of the RR exceeded 20% of the threshold RR.

Results

Between April 2002 and July 2003, 45 eligible patients were registered and analyzed. Among the 45 patients, 40 (89%) had previously received chemotherapy for metastasis and 24 (53%) had a performance status (PS) of 0. Thirteen partial responses were obtained among the 45 patients, resulting in an overall RR of 29% (95% CI, 16?C42%). The median time to progression was 4.1?months, and the median survival time was 10?months, with a 1-year survival rate of 36%. Grade 4 neutropenia was observed in 29% of the patients, whereas febrile neutropenia occurred in 9%. The incidence rates of grade 3 nausea and diarrhea were 13 and 2%, respectively.

Conclusions

Although this study did not achieve the per-protocol definition of activity, the progression-free survival and overall survival appeared to be promising, with acceptable tolerability. Thus, MMC/CPT-11 therapy as second-line chemotherapy for fluoropyrimidine-resistant advanced gastric cancer presents a potential treatment option in patients with a good PS.     

First-line bolus 5-fluorouracil plus leucovorin for peritoneally disseminated gastric cancer with massive ascites or inadequate oral intake

Background

There are few chemotherapeutic options for advanced gastric cancer with severe disseminated peritoneal metastases, which are usually accompanied by ascites. Bolus 5-fluorouracil (5-FU) plus leucovorin therapy has been widely used against gastrointestinal malignancies, with resulting mild toxicities.

Methods

We retrospectively analyzed the efficacy and safety of first-line chemotherapy with bolus 5-FU plus l-leucovorin in 30 advanced gastric cancer patients who had massive ascites and/or inadequate oral intake. This therapy consisted of 5-FU (600 mg/m² IV bolus) plus l-leucovorin (250 mg/m² 2-h IV infusion) administered on a 6 weeks on/2 weeks off schedule.

Results

Among all the patients, 26 (87%) were unable to eat and 12 (40%) had massive ascites. Major grade 3 or 4 adverse events were neutropenia (17%), nausea (7%), fatigue (7%), and diarrhea (3%); no treatment-related deaths were observed. The median progression-free survival and overall survival (OS) were 2.4 months [95% confidence interval (CI), 0.6–4.1] and 6.0 months (95% CI, 2.1–9.9), respectively. Objective improvement in oral intake was seen in 7 patients (27%). Improvement in ascites occurred in 9 (39%) of 23 patients. In multivariate analyses, the presence of both massive ascites and inadequate oral intake was significantly associated with worse OS (hazard ratio, 5.25; 95% CI, 1.61–17.1). The median OS for patients (n = 22) without this factor was 7.2 months (95% CI, 4.2–10.3).

Conclusion

Our study suggests that bolus 5-FU plus l-leucovorin therapy is feasible and has clinical activity as palliative therapy in patients with severe peritoneal metastases from gastric cancer.

     

Phase II study of cisplatin and 5-fluorouracil with concurrent radiotherapy in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group trial (JCOG9516)

BACKGROUND: In Japan, concurrent chemoradiotherapy is the standard treatment for unresectable esophageal cancer. The optimal combination of chemotherapeutic agents and radiotherapy dose remains controversial. The present study consists of a phase II trial of a cisplatin (CDDP)/5-fluorouracil (5-FU) infusion with concurrent radiotherapy in patients with unresectable, advanced esophageal cancer. METHODS: Between March 13, 1996, and April 28, 1998, 60 patients with advanced squamous cell carcinoma of the thoracic esophagus having either T4 tumor or distant lymph node metastasis (M1 Lym) were enrolled in this study. CDDP 70 mg/m(2) was administered on days 1 and 29, and 5-FU 700 mg/m(2)/day was administered on days 1-4 and 29-32. Fractionated radiotherapy was performed on days 1-21 and 29-49; a total dose of 60 Gy was delivered at the rate of 2 Gy per fraction. RESULTS: The overall response rate of all the 60 registered patients was 68.3% (41/60), and the complete response rate was 15% (9/60). The median survival time was 305.5 days, and the 2-year survival rate was 31.5%. One toxicity-related death occurred. The major form of toxicity exceeding grade 2 was found to be myelosuppression; grade 4 toxicity was observed in five patients. CONCLUSION: Based on the overall response rate, the results obtained from the present trial do not appear to be promising. However, it is currently suitable for the treatment of patients with unresectable, advanced esophageal cancer because of certain clinical advantages, a higher CR rate and a lower incidence of fistula formation. A phase II/III trial will be started in order to compare low-dose continual CDDP/5-FU infusion and concurrent radiotherapy with the results obtained in this study.     

Phase II study of Adriamycin with sequential methotrexate and 5-fluorouracil (AMF) in gastric carcinoma

Summary The purpose of this study was to evaluate the response rate, methotrexate plasma levels, and toxicity of a three-drug regimen in patients with gastric carcinoma. A total of 37 patients with advanced measurable adenocarcinoma of the stomach were treated with Adriamycin, methotrexate, and 5-fluorouracil (AMF). Adriamycin and methotrexate were given as i.v. infusions on day 1; 24 h following methotrexate administration, patients received an i.v. infusion of 5-fluorouracil concomitantly with oral leukovorin factor (given over 48 h). Methotrexate levels were monitored regularly in all patients, and courses were repeated every 3 weeks. The median dose levels per course were 50 mg/m² (range, 40–60 mg/m²) for Adriamycin, 1,000 mg/m² (range, 650–1,250 mg/m²) for 5-fluorouracil, and 500 mg/m² (range, 160–625 mg/m²) for methotrexate. Of 36 evaluable patients, 8 (22%) achieved an objective response, including 1 complete remission. Stable disease was noted in 11 patients and a minor tumor regression occurred in 1. The median survival duration of all patients was 6 months (range, 2–31 + months). AMF was well tolerated; toxicities were mild to moderate, most frequently involving nausea and vomiting, mucositis, and neutropenia with or without fever. There was no death directly attributable to chemotherapy. Although the AMF regimen used a well-documented preclinical concept of synergism between methotrexate and 5-fluorouracil, response and survival results suggest a modest activity of this combination in patients with gastric cancer. Better preclinical models are necessary for the development of effective combination chemotherapy.     

Long-term results for patients with unresectable gastric cancer who received chemotherapy in the Japan Clinical Oncology Group (JCOG) trials

Background. Despite recent developments in chemotherapeutic trials, the long-term results of chemotherapy remain to be clarified. We evaluated the impact of chemotherapy on long-term survival in patients with unresectable gastric cancer. Methods. Between 1985 and 1991, a total of 363 patients with gastric cancer were enrolled into a single randomized phase II study and into three series of phase II studies of the Japan Clinical Oncology Group. The chemotherapy regimens consisted of tegafur + mitomycin C (FTM), uracil-tegafur + mitomycin C (UFTM), 5′deoxy-flurorouridine + cisplatin (5′P), etoposide + doxorubicin + cisplatin (EAP), and 5-fluorouracil + cisplatin (FP). After a review of the 363 patients' case records, 226 patients who fulfilled the criteria of having "unresectable" factors prior to chemotherapy became the subjects for this analysis. Of the 226 patients, 50 were in the FTM regimen group, 39, in the UFTM; 49, in the 5′P; 42, in the EAP; and 46, in the FP group. Survival was updated continually. Results. Of the 226 patients, 22 (10%) survived longer than 2 years, and 8 (4%) have survived longer than 5 years. The 8 5-year survivors consisted of 6 patients who had para-aortic node metastases alone as an "unresectable factor", 1 who had para-aortic and cervical node metastases, and the remaining patient who had liver metastasis alone. Twenty-nine patients with para-aortic node metastasis alone had a significantly longer survival than the other 197 patients (P < 0.001). Conclusion. Systemic chemotherapy may offer some hope of achieving long-term survival in patients with unresectable gastric cancer, particularly when the patient has metastasis only to para-aortic nodes. Revieved: July 24, 2000 / Accepted: November 7, 2000     

Phase II study of biweekly paclitaxel and cisplatin combination chemotherapy in advanced gastric cancer: Korea Japan Collaborative Study Group Trial

BACKGROUND: Benefits of chemotherapy have generally been modest in gastric cancer, although those regimens developed more recently have produced higher response rates. Paclitaxel plus cisplatin is one such regimen and divided administration of paclitaxel has been suggested to be associated with lower neurological and hematologic toxicities and be able to achieve higher paclitaxel dose intensities than paclitaxel administration at 175 mg/m2 every 3 weeks. This study was undertaked to assess the efficacy and toxicity of a biweekly paclitaxel and cisplatin combination treatment in advanced gastric cancer. METHODS: Twenty-five patients from Japan and Korea, 50 patients in total, were entered into this trial which was conducted from October 2004 to June 2005. Median age of the patients was 57 years (range: 26-78). Paclitaxel 140 mg/m2 was administered intravenously on days 1 and 15 of each 4-week cycle. Cisplatin 30 mg/m2 was also administered on days 1 and 15 with standard hydration. A total of 278 courses of treatment (two treatment courses per cycle) were conducted for 50 patients. The median number of treatment cycles per patient was two with a range of one to six. RESULTS: Nine of the 50 patients responded to the treatment, with an overall objective response rate of 18% (95% CI, 12-41), which included one complete response. Two patients were not evaluable and 14 patients had stable disease as best response. The median survival duration of the 50 patients was 333 days (range: 52-637+ days). The main toxicity was neutropenia. Significant toxicity (NCI-CTC grade 3 or 4) included neutropenia in 19 patients (38%), anorexia in four (8%), infection in three (6%), anemia in three (6%), and abdominal pain in three (6%). CONCLUSIONS: Biweekly paclitaxel and cisplatin combination chemotherapy showed modest activity in advanced gastric carcinoma with a favorable toxicity pattern.     

A phase II study of doxifluridine in elderly patients with advanced gastric cancer: the Japan Clinical Oncology Group Study (JCOG 9410)

BACKGROUND: A previous phase II study of doxifluridine in non-elderly patients with advanced gastric cancer demonstrated a favorable survival with mild toxicity, despite a low response rate. The objectives of this study were to evaluate efficacy and feasibility of this agent for elderly patients. METHODS: This study protocol required elderly patients, aged 76-80 years, with advanced gastric cancer and having no prior chemotherapy. Doxifluridine, at a dose of 1400 mg/m(2)/day, was administered for four consecutive days followed by a 10-day rest. RESULTS: Between October 1994 and March 1998, 18 patients were registered. The study was then closed because of poor accrual. Toxicity was moderate; three patients suffered from grade 3 anemia and one patient each had grade 3 thrombocytopenia, nausea/vomiting and grade 4 diarrhea. There was one partial response, seven with no change and 10 with progressive disease, yielding a response rate of 5.6%. The median progression-free survival and median survival time for the 18 patients were 55 and 164 days, respectively, with a 1-year survival rate of 5.6%. CONCLUSIONS: Although the number of patients was too small to draw any definitive conclusions, this study failed to demonstrate the survival advantage of doxifluridine.     

A phase-II trial of dose-dense chemotherapy in patients with disseminated thymoma: report of a Japan Clinical Oncology Group trial (JCOG 9605)

Background:

To evaluate the safety and efficacy of dose-dense weekly chemotherapy in the treatment of advanced thymoma.

Methods:

Subjects comprised patients with histologically documented chemotherapy-naïve thymoma with stage-IVa or IVb disease. Thymic carcinoma, carcinoid or lymphoma cases were excluded. Patients received 9 weeks of chemotherapy: cisplatin (25 mg m⁻²) on weeks 1–9; vincristine (1 mg m⁻²) on weeks 1, 2, 4, 6 and 8; and doxorubicin (40 mg m⁻²) and etoposide (80 mg m⁻²) on days 1–3 of weeks 1, 3, 5, 7 and 9. Chemotherapy courses were supported by granulocyte colony-stimulating factor. Post-protocol local therapy was allowed.

Results:

From July 1997 to March 2004, 30 patients were entered. Three were ineligible due to different histology. Chemotherapy-associated toxicity was mainly haematological and was well tolerated, with no deaths due to toxicity, and 87% of patients completed the planned 9-week regimen. Overall response rate was 59%, with 16 of the 27 eligible patients achieving partial response. Median progression-fee survival (PFS) was 0.79 years (95% confidence interval: 0.52–1.40 years), and PFS at 1 and 2 years was 37 and 15%, respectively. Overall survival rates at 2 and 5 years were 89 and 65%, respectively.

Conclusion:

In stage-IV thymoma patients, weekly dose-dense chemotherapy offers similar activity to conventional regimens.     

Phase II Study of Cisplatin and 5-Fluorouracil with Concurrent Radiotherapy in Advanced Squamous Cell Carcinoma of the Esophagus: a Japan Esophageal Oncology Group (JEOG)/Japan Clinical Oncology Group Trial (JCOG9516)

The above article     

A Phase II study of irinotecan in combination with 120-h infusion of 5-fluorouracil in patients with metastatic colorectal carcinoma: Japan Clinical Oncology Group Study (JCOG9703)

PURPOSE: To evaluate the antitumor effect and feasibility of a combination of irinotecan (CPT-11) and 5-day infusional 5-fluorouracil (5-FU) in a sequential schedule based on our previous combination phase I studies in patients with metastatic colorectal cancer. PATIENTS AND METHODS: Forty chemotherapy-naive patients with metastatic colorectal cancer received 90-min infusion of CPT-11 at a dose of 150 mg/m(2) on days 1 and 15 and 120-h protracted infusion of 5-FU at 600 mg/m(2)/day on days 3-7, which were repeated every 4 weeks. RESULTS: The median number of actually administered courses was five, ranging from one to 14. There were 16 (40%) patients who developed grade 3 or 4 neutropenia. Grade 3 or 4 nausea/vomiting and diarrhea were seen in three (8%) and seven (18%) patients, respectively. Only one early death not related to treatment occurred during the study. There was one complete response and 17 partial responses with a response rate of 45% (95% confidence interval: 29.3-61.5%). With a median follow-up period of 22.5 months for survivors, the median survival and median progression-free survival times were 15.9 and 7.0 months, respectively. CONCLUSIONS: Although the toxicities were modest, this sequentially combined regimen is active and feasible in patients with metastatic colorectal cancer.     

Phase III study to evaluate the use of high-dose chemotherapy as consolidation of treatment for high-risk postoperative breast cancer: Japan Clinical Oncology Group study, JCOG 9208

A randomized controlled trial was conducted to evaluate the efficacy of high-dose chemotherapy (HDC) as consolidation of the treatment of high-risk postoperative breast cancer. Patients under 56 years of age with stage I to IIIB breast cancer involving 10 or more axillary lymph nodes were eligible. The primary endpoint was relapse-free survival (RFS). Between May 1993 and March 1999, 97 patients were enrolled, and two patients became ineligible. The median age of the 97 patients was 46 years (range 27–55 years), and 72 (74%) were premenopausal. The median number of involved axillary nodes was 16 (range 10–49). All patients had undergone a radical mastectomy. Major characteristics were well balanced between the treatment arms. Forty-eight patients in the standard-dose (STD) arm received six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen. Forty-nine patients were assigned to undergo HDC with cyclophosphamide and thiotepa after six courses of cyclophosphamide, doxorubicin, and 5-fluorouracil followed by tamoxifen; however, 15 of these patients (31%) did not undergo HDC. HDC was well tolerated without any treatment-related mortality. At a median follow-up of 63 months, the 5-year RFS of 47 eligible patients in the STD arm and 48 eligible patients in the HDC arm was 37% and 52% on an intent-to-treat basis, respectively ( P  = 0.17). Five-year overall survival of all randomized patients was 62% for the STD arm and 63% for the HDC arm ( P  = 0.78). Although the prespecified values of the two arms were not so accurate as to allow detection of the observed difference, no advantage of HDC was observed in terms of RFS or overall survival. ( Cancer Sci 2008; 99: 145–151)     

An EORTC Gastrointestinal Group evaluation of the combination of sequential methotrexate and 5-fluorouracil, combined with adriamycin in advanced measurable gastric cancer

In a phase II multicenter trial, 71 patients with advanced measurable gastric cancer were registered to receive sequential high-dose methotrexate (MTX) and 5-fluorouracil (5-FU) combined with Adriamycin (A [Adria Laboratories, Columbus, OH]). The response rate was 33% (22 of 67), including all eligible patients. There were nine complete responders (CRs). The median survival for all patients was 6 months. There has been one toxic death; however, three other patients died from toxicity associated with major protocol violations. It is concluded that this protocol is active in gastric cancer. Toxicity, partly because of nonprotocol adherence, is considerable and is now under further investigation in a randomized trial comparing this schedule with a combination of 5-FU, Adriamycin, and mitomycin C (FAM).     

Survival prolongation after treatment failure of first-line chemotherapy in patients with advanced gastric cancer: combined analysis of the Japan Clinical Oncology Group Trials JCOG9205 and JCOG9912

Background

Two randomized phase III trials of first-line chemotherapy for advanced gastric cancer (JCOG9205 and JCOG9912) conducted by the Japan Clinical Oncology Group used 5-fluorouracil continuous infusion (5-FUci) as the control arm. New active agents (e.g., S-1, irinotecan, and taxanes) were introduced as second-line chemotherapy in the late 1990s after JCOG9205. This combined analysis evaluated whether patients in the 5-FUci arm of JCOG9912 exhibited better survival after adjusting for baseline factors and also investigated the cause of survival prolongation.

Patients and methods

The subjects were patients assigned to the 5-FUci arms who met the eligibility criteria of both JCOG9205 and JCOG9912. Overall survival (OS), time to treatment failure (TTF), and survival after treatment failure in the first-line chemotherapy (OS-TTF) were compared after adjusting baseline characteristics using the Cox proportional hazard model. Second-line chemotherapy details were also reviewed.

Results

The combined analysis included 89 and 230 patients in JCOG9205 and JCOG9912, respectively. After adjusting baseline characteristics, TTF was similar between groups (HR 0.95; 95 % CI, 0.73–1.26). However, both OS (HR, 0.74; 95 % CI, 0.56–0.99) and OS-TTF (HR, 0.76; 95 % CI, 0.57–1.01) were longer in JCOG9912. More patients in JCOG9912 received second-line chemotherapy (83 vs. 52 %) with new drugs (77 vs. 10 %) than in JCOG9205. OS-TTF was substantially prolonged in patients who received second-line chemotherapy (HR, 0.66; 95 % CI, 0.46–0.95).

Conclusion

OS and OS-TTF were longer in JCOG9912 than JCOG9205. Second-line chemotherapy with new drugs is a potential reason for the observed prolongation of survival.     

Long-term survival and prognostic factors in patients with metastatic gastric cancers treated with chemotherapy in the Japan Clinical Oncology Group (JCOG) study

BACKGROUND: The long-term survival of patients after chemotherapy for advanced gastric cancer remains unclear. The aim of this analysis was to investigate prognostic factors for patients with metastatic gastric cancer treated by chemotherapy, and to identify the characteristics of long-term survivors. METHODS: Six hundred and forty three patients were enrolled in four phase II studies and one phase III study by the Japan Clinical Oncology Group between January 1985 and April 1997. By adjusting patients' eligibility between the five studies, 497 patients (77%) were selected for the analysis. Univariate and multivariate analyses were performed using log-rank tests and Cox's proportional hazard model, respectively. RESULTS: Of the 497 patients analyzed, 39 (8%) and 11 (2%) patients have survived longer than 2 and 5 years, respectively. By multivariate analysis, better performance status, a small number of metastatic sites and macroscopically non-scirrhous type tumors were significantly associated with better prognosis. Characteristics of the 11 5-year survivors revealed eight with para-aortic node metastases alone. Eight of these patients received gastrectomy; four underwent it before chemotherapy, and the other four patients received it after achieving downstaging with successful chemotherapy. CONCLUSIONS: These results demonstrated that better performance status, a small number of metastatic sites and macroscopically non-scirrhous type tumors are independent favorable factors for survival. There were a few 5-year survivors with unresectable gastric cancers, most of whom had only abdominal lymph node metastases and received gastrectomy before or after chemotherapy.     

Phase II evaluation of protracted infusion of cisplatin and 5-fluorouracil in advanced squamous cell carcinoma of the esophagus: a Japan Esophageal Oncology Group (JEOG) Trial (JCOG9407).

BACKGROUND: Surgery for advanced esophageal carcinoma has its limits as regards aggressiveness and therapeutic effect, therefore effective multimodality treatment is required to obtain better survival. The objective of this study was to evaluate whether daily continuous infusion of CDDP could achieve a higher clinical response rate with less toxicity than its drip infusion in the previous phase II study that we had conducted. METHODS: Patients with primary extensive or relapsed esophageal carcinoma after esophagectomy, which had distant organ metastasis and histologically proven SCC, were eligible for this study. A dose of 20 mg/m(2) of cisplatin and 800 mg/m(2) of 5-fluorouracil was given by continuous infusion for 24 h on days 1-5. This treatment was repeated every 4 weeks for up to four cycles. A total of 36 men and six women with a median age of 64 (range 39-75) years were registered and 36 patients were eligible. RESULTS: The overall response rate of the registered patients was 33.3% (12/36) and the median response duration was 175 days. Median survival time was 201.5 days and the 1-year survival rate was 27.8%. Change from bolus to continuous infusion of cisplatin affected neither the type nor the degree of toxicity. CONCLUSION: Daily continuous infusion of cisplatin was not associated with higher response or lower toxicity than those seen with the high-dose bolus or multibolus treatment regimens. We conclude that this regimen in this setting is not worthy of further phase III trials. JEOG is now evaluating other drug combination regimens.     

Phase II trial of S-1 for neoadjuvant chemotherapy against scirrhous gastric cancer (JCOG 0002)

Background  The prognosis of scirrhous gastric cancer remains poor despite extended surgery or adjuvant or neoadjuvant chemotherapy. A pilot study of S-1 (TS-1; Taiho Pharmaceutical, Tokyo, Japan), an oral 5-fluorouracil derivative, for neoadjuvant chemotherapy unexpectedly showed good response and a promising effect on survival. Therefore, the Japan Clinical Oncology Group conducted a phase II trial to confirm the efficacy of S-1 for neoadjuvant chemotherapy against resectable scirrhous gastric cancer. Methods  Patients were eligible if they had typical scirrhous gastric cancer invading more than half of the stomach, and resectable disease confirmed by laparoscopic staging. The treatment schedule consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 (100–120 mg/body per day), followed by radical surgery. Results  Fifty-five eligible patients were registered. Three completed only one course of the neoadjuvant chemotherapy, whereas 52 completed two courses. Toxicity was acceptable, with a few grade 3 (5.5%) events, but no grade 4 adverse events. The response rate was 32.6% in 43 evaluable patients. Of the 55 patients, 2 refused operation, 1 developed lung metastasis, and 52 underwent laparotomy. The curative resection rate was 80.8%, with acceptable morbidity and no mortality. The survival curve at 2 years’ follow up showed a better survival rate than that of the historical controls, but did not reach the expected survival rate. Conclusion  S-1 neoadjuvant chemotherapy appeared feasible and showed positive effects against scirrhous gastric cancer; however, the survival rate with S-1 did not reach the expected rate required when selecting an agent for a phase III trial to confirm the effectiveness of neoadjuvant chemotherapy against scirrhous gastric cancer. (on behalf of the Gastric Cancer Surgery Study Group of the Japan Clinical Oncology Group)     

A Phase II study of systemic chemotherapy with docetaxel, cisplatin, and S-1 (DCS) followed by surgery in gastric cancer patients with extensive lymph node metastasis: Japan Clinical Oncology Group study JCOG1002

A Phase II trial was initiated in Japan to evaluate the efficacy and safety of preoperative chemotherapy with docetaxel, cisplatin and S-1 for gastric cancer with extensive lymph node metastasis. Patients are eligible to participate in the study if they have para-aortic lymph node metastases (stations no. 16a2/16b1) and/or a bulky lymph node (≥3 cm × 1 or ≥1.5 cm × 2) along the celiac, splenic, common or proper hepatic arteries or the superior mesenteric vein, while patients with other distant metastases are ineligible. A total of 50 patients will be enrolled over 2.5 years. The primary endpoint is the response rate of the preoperative chemotherapy, which will be assessed based on the Response Evaluation Criteria in Solid Tumors ver. 1.0. The secondary endpoints are %3-year survival, %5-year survival, proportion of patients with R0 resection, proportion of patients who complete the preoperative chemotherapy and surgery, proportion of patients who complete the protocol treatment, pathological response rate and adverse events. This trial was registered at the UMIN Clinical Trials Registry (www.umin.ac.jp/ctr/) as UMIN000006069.