Recurrent Gastric Adenocarcinoma Research Articles

Second-line chemotherapy with paclitaxel for elderly patients with advanced gastric cancer.

108 Background: Survival benefits of second-line chemotherapy such as weekly paclitaxel (wPTX) for patients with advanced gastric cancer (AGC) were shown in several phase 3 trials. However, these trials included a small proportion of elderly patients, and few elderly patients receive second-line therapy in clinical practice. The aim of this study was to compare the efficacy and safety of second-line chemotherapy with wPTX between elderly and non-elderly patients. Methods: The subjects of this retrospective study were AGC patients who received wPTX as second-line chemotherapy between January 2002 and August 2014, fulfilling the following selection criteria; 1) pathologically proven metastatic or recurrent gastric adenocarcinoma, 2) receipt of wPTX after platinum or fluoropyrimidine containing chemotherapy. Patients were divided into two groups by age: ≥ 75 years old (elderly group) and < 75 years old (non-elderly group). Response rate (RR) in patients with measurable lesions, overall survival (OS), progression-free survival (PFS), post-progression survival (PPS) and adverse events were evaluated. Hazard ratios of survival were adjusted by prognostic factors using Cox proportional hazard model. Results: A total of 272 patients, 31 elderly and 241 non-elderly, were selected in this study. RRs were 6.2% (1/16) in the elderly group and 12.7% (15/118) in the non-elderly group (p = 0.69). While PFS was similar between two groups (median 2.4 vs. 3.6 months, adjusted hazard ratio [HR] 1.18, p = 0.46), the elderly group showed shorter OS than the non-elderly group (median 5.1 vs. 6.1 months, adjusted HR 1.49, p = 0.06), associated with relatively shorter PPS (median 2.2 vs. 2.6 months, adjusted HR 1.40, p = 0.11). There were no remarkable differences in the incidences of grade 3 or higher adverse events between the two groups (hematologic 38.7 vs. 41.1%; non-hematologic 25.8 vs. 23.7%). No treatment related deaths were observed in either group. Third-line chemotherapy was administered in 19.4% of elderly group and 35.3% of non-elderly group (p = 0.11). Conclusions: It is suggested that second-line chemotherapy with wPTX for AGC may be tolerable and have some clinical benefits for elderly patients as well as for non-elderly patients.

Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS)

BackgroundFive-weekly S-1 plus cisplatin (SP5) is one of the standard first-line regimens for advanced gastric cancer (GC), proven in a Japanese phase III study. To enhance the dose intensity of cisplatin, 3-weekly S-1 plus cisplatin (SP3) was developed. Patients and methodsThis multicenter, randomized, open-label, phase III study evaluated whether SP3 (S-1 80 mg/m2/day on days 1–14 and cisplatin 60 mg/m2 on day 1) was noninferior/superior to SP5 (S-1 80–120 mg/day on days 1–21 and cisplatin 60 mg/m2 on day 1 or 8) in terms of progression-free survival (PFS). Chemotherapy-naive patients with metastatic, recurrent gastric or gastroesophageal junction adenocarcinoma were randomized 1 : 1 to receive either SP3 or SP5. The trial is registered at ClinicalTrials.gov (NCT00915382). ResultsBetween February 2009 and January 2012, 625 patients were randomized at 42 sites in Korea and Japan. With a median follow-up duration of 32.4 months (range, 13.3–48.6 months) in surviving patients, SP3 was not only noninferior but also superior to SP5 in terms of PFS [median 5.5 versus 4.9 months; hazard ratio (HR) = 0.82; 95% confidence interval (CI) 0.68–0.99; P = 0.0418 for superiority). There was no difference in overall survival (OS) between the groups (median 14.1 versus 13.9 months; HR = 0.99; 95% CI 0.81–1.21; P = 0.9068). In patients with measurable disease, the response rates were 60% in the SP3 arm and 50% in the SP5 arm (P = 0.065). Both regimens were generally well tolerated, but grade 3 or higher anemia (19% versus 9%) and neutropenia (39% versus 9%) were more frequent in SP3. ConclusionsSP3 is superior to SP5 in terms of PFS. However, since the improvement in PFS was only slight and there was no difference in OS, both SP3 and SP5 can be recommended as first-line treatments for patients with advanced GC.

Combination Chemotherapy with S-1 and Oxaliplatin (SOX) as First-Line Treatment in Elderly Patients with Advanced Gastric Cancer.

This study is a retrospective analysis evaluating the efficacy and toxicity of combination chemotherapy with S-1 and oxaliplatin (SOX) as first-line treatment in elderly patients with advanced gastric cancer. One hundred and twenty-nine patients with recurrent or metastatic gastric adenocarcinoma were treated with SOX; S-1 (40-60 mg depending on patient's body surface area) was given orally, twice daily on days 1 to 14 followed by a 7-day rest period, 130 mg/m(2) oxaliplatin was given as an intravenous infusion over 2-hours on day one. The cycle was repeated every three weeks. All of the patients were older than 65 years. Among 129 patients enrolled, nine patients could not be evaluated for responses because of the absence of any measurable lesions or early discontinuation of therapy. Assessment of the response of 120 patients was made. The overall objective response rate was 54.2 % (95 %CI, 45.3-63.1 %), with three complete responses and 62 partial responses. The disease control rate was 80.8 % (95 %CI, 73.8-87.8 %). The median follow-up period was 23 months (range, 5-42 months). The median time to progression was 6.9 months (95 %CI, 5.5-8.3 months) and the median overall survival was 12.8 months (95 %CI, 11.4-14.2 months). The one-year survival rate was 57.5 % (95 %CI, 48.7-66.3 %). In 129 patients assessed safety, grade 3 and 4 toxicities included leucopenia (20.9 %), neutropenia (24.0 %), anemia (10.9 %), thrombocytopenia (10.1 %), anorexia (3.1 %), peripheral neurotoxicity (15.5 %), and fatigue (12.4 %). No treatment-related deaths occurred. Combination chemotherapy with SOX offers an effective, safe and well-tolerated regimen for elderly patients with advanced gastric cancer.

Docetaxel plus oxaliplatin with or without fluorouracil or capecitabine in metastatic or locally recurrent gastric cancer: a randomized phase II study

BackgroundDocetaxel/cisplatin/infusional 5-fluorouracil (5-FU; DCF) is a standard chemotherapy regimen for patients with advanced gastric cancer (GC). This phase II study evaluated docetaxel/oxaliplatin (TE), docetaxel/oxaliplatin/5-FU (TEF), and docetaxel/oxaliplatin/capecitabine (TEX) in patients with advanced GC. Patients and methodsPatients with metastatic or locally recurrent gastric adenocarcinoma (including carcinoma of the gastro-oesophageal junction) were randomly assigned (1 : 1 : 1) to TE, TEF, or TEX. Each regimen was tested at two doses before full evaluation at optimized dose levels. The primary end point was progression-free survival (PFS). Overall survival (OS), tumour response, and safety were also assessed. A therapeutic index (median PFS relative to the incidence of febrile neutropenia) was calculated for each regimen and compared with DCF (historical data). ResultsOverall, 248 patients were randomly assigned to receive optimized dose treatment. Median PFS was longer with TEF (7.66 [95% confidence interval (CI): 6.97–9.40] months) versus TE (4.50 [3.68–5.32] months) and TEX (5.55 [4.30–6.37] months). Median OS was 14.59 (95% CI: 11.70–21.78) months for TEF versus 8.97 (7.79–10.87) months for TE and 11.30 (8.08–14.03) months for TEX. The rate of tumour response (complete or partial) was 46.6% (95% CI 35.9–57.5) for TEF versus 23.1% (14.3–34.0) for TE and 25.6% (16.6–36.4) for TEX. The frequency and type of adverse events (AEs) were similar across the three arms. Common grade 3/4 AEs were fatigue (21%), sensory neuropathy (14%), and diarrhoea (13%). Febrile neutropenia was reported in 2% (TEF), 14% (TE), and 9% (TEX) of patients. The therapeutic index was improved with TEF versus TEX, TE, or DCF. ConclusionThese results suggest that TEF is worthy of evaluation as an arm in a phase III trial or as a backbone regimen for new targeted agents in advanced GC. ClinicalTrials.gov IdentifierTrial registration number: NCT00382720.

P-0042 - Efficacy and Safety of Triweekly Docetaxel, Oxaliplatin, Fluorouracil, and Folinic Acid (DOFF) in Patients with Advanced Gastric or Gastroesophageal Adenocarcinoma

Introduction: Docetaxel, cisplatin, fluorouracil (DCF) regimen improved response rate, quality of life and survival for patients with advanced gastric cancer, but is limited by significant toxicity. In attempt to reduce the toxicity of DCF, we evaluated the efficacy and tolerability of docetaxel associated with oxaliplatin and fluorouracil in a triweekly schedule. Methods: Patients with histologically confirmed locally advanced, recurrent or metastatic gastric or esophagogastric adenocarcinoma treated in our center were reviewed. Patients received docetaxel 75 mg/m2, oxaliplatin 100mg/m2 on day 1, and fluorouracil 400mg/m2 in 2 hours intravenous infusions from day 1 to day 5 preceded by Folonic acid 200mg/m2, every 3 weeks. Responses were evaluated every three cycles according to RECIST criteria and toxicities were graded according to NCI-CTC- AE v3 scale. Results: Twenty two patients were included in this study. Median age was 59 years [range: 35-79]. The majority (77.3%) of patients had good (0-1) Performance Status (ECOG scale). Primary tumor location was the stomach in 16 patients (72.7%) and the esophagogastric junction in 6 (27.3%). Disease was locally advanced in 7 patients (31.8%) and metastatic in 15 patients (68.2%). The most common sites of metastasis were lymph nodes (66.6%), liver (46.6%) and peritoneum (40%). Treatment was administrated as first line in 17 patients (77.3%) and second line in 5 patients (22.7%). Median number of cycles received was 6 [range: 2-12]. Grade 3 or 4 hematological toxicities consisted in neutropenia (18.2%) and anemia (4.5%). Febrile neutropenia was observed in two patients (9.1%). Main G3-4 non hematological toxicities were diarrhea (13.6%) and peripheral neuropathy (13.6%). Dose reductions of drugs were required in fifteen patients (68.2%) but there were no treatment-related deaths. Eighteen patients (81.8%) had measurable disease; objective response rate was 50% with a complete response in four patients (22.2%) and partial response in 5 (27.8%). Stable disease was observed in one patient (5.5%). After a median follow-up of 15.2 months, 9 patients (40.9%) had died. Median time to progression was 4.2 months. The disease control rate at 6 months was 36.4%. Tumor downstaging allowed curative surgery in 5 of the seven patients (71.1%) with locally advanced disease initially considered as unresectable. Conclusion: Triweekly Docetaxel, Oxaliplatin, Fluorouracil and Folinic acid (DOFF) has an acceptable safety profile for patients with advanced gastric or esophagogastric cancer and could favor tumor resection in the neoadjuvant setting.

β-Tubulin is a Predictive Marker of Docetaxel Combined with S-1 in Recurrent or Metastatic Gastric Cancer

Aim: The aim of this study was to evaluate efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with recurrent or metastatic gastric cancer, and to investigate whether β-tubulin protein expression level is a predictive or prognostic factor. Methods: From March 2010 to December 2011, 90 patients from Medical Oncology Department of Shanghai Zhongshan Hospital, Fudan University, were enrolled in this study. Patients with recurrent or metastatic gastric adenocarcinoma were treated with docetaxel of 40 mg/m2 intravenously on day 1 and S-1 of 80 mg/m2 orally for 14 days with one-week intermission as first-line chemotherapy. The chemotherapeutic effects were evaluated every 3 cycles using the Response Evaluation Criteria In Solid Tumors (RECIST1.1). The tumor tissues and the serum of peripheral blood were obtained at the start of the study to analyze the protein expression level of β-tubulin, which were estimated using immunohistochemistry (IHC) and enzyme-linked immunosorbent assay (ELISA), respectively. Response and toxicity were analyzed. All the patients were followed-up until the time of progression, death, or the censored time, to calculate progression-free survival (PFS) and overall survival (OS) time. Results: In total, 90 patients (median age: 60.5 years [range: 28–76 years]) received a total of 491 treatment cycles (median: 6 [range: 2–9]) of docetaxel combined with S-1 chemotherapy, and 291 cycles of single S-1- maintenance treatment. Three complete response (CR) and thirty-eight partial responses (PR) were observed, with an overall response rate (ORR) of 45.1%. Median OS was 12.5 months, and median PFS was 7.0 months. PFS and OS in patients with peritoneal metastases were significantly longer compared to patients with other metastatic loci. β-tubulin protein expression levels in tumor tissue and in serum were significantly lower in responders than in nonresponders. Lower expression of β-tubulin protein in serum but not in tumor tissues was associated with more serious toxicities.There was significant correlation between tumor tissues and peripheral blood about the expression of β-tubulin. Peritoneal metastasis was an independent prognostic factor by COX regression. PFS and OS were not correlated with β-tubulin expressive level. Conclusion: This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with recurrent or metastatic gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline expression levels of β-tubulin could predict the response. β- tubulin is a predictive marker.

Phase III trial of a 3-weekly versus 5-weekly schedule of S-1 plus cisplatin (SP) combination chemotherapy for first-line treatment of advanced gastric cancer (AGC): SOS study.

LBA4024 Background: 5-weekly S-1 plus cisplatin (SP5: S-1 80-120 mg/body/day on D1-21, cisplatin 60 mg/m2 on D8, every 5 weeks) has become a standard first-line chemotherapy for AGC in Japan based on the SPIRITS trial (Lancet Oncol. 2008;9:215). To strengthen the low-dose intensity of cisplatin in this SP5 for greater efficacy, a 3-weekly S-1 plus cisplatin (SP3: S-1 80 mg/m2/day on D1-14, cisplatin 60 mg/m2on D1, every 3 weeks) has been developed in Korea (Cancer Chemother Pharmacol. 2008;61:837). Methods: This SOS study was a multicenter, randomized, open-label, phase III study to evaluate whether SP3 was non-inferior/superior to SP5 in terms of progression-free survival (PFS) determined by a blinded central radiology review according to RECIST v1.1. Patients (pts) with metastatic or recurrent gastric or gastroesophageal junction adenocarcinoma and with no prior chemotherapy were randomized 1:1 to receive either SP3 or SP5 until disease progression or unacceptable toxicities. Results: Between February 2009 and January 2012, a total of 625 pts were randomized from 42 sites in Korea and Japan. Median age was 59.6 years. 99% of pts had ECOG performance status 0-1. 16% of pts had prior gastrectomy. 62% of pts had measurable lesions. With a median follow-up of 34.7 months (range, 14.2-48.8) in surviving pts, SP3 was significantly noninferior and superior to SP5 in PFS (median 5.5 months vs. 4.9 months; HR 0.82, 95% CI 0.68-0.99, p=0.0418). Overall response rate (ORR) was also better with SP3 than with SP5 (60% vs. 50%, p=0.029). However, OS of both groups was equivalent (median 14.1 vs. 13.9 months; HR 0.99, 95% CI 0.81-1.21, p=0.9068). Treatment was well tolerated in both arms, while SP3 was associated with more frequent G3/4 anemia (19% vs. 9%) and neutropenia (39% vs. 9%). Dose intensity was higher in SP3 than in SP5 for both agents (median 331 vs. 317 mg/m2/week for S-1, p<0.001; median 18 vs. 12 mg/m2/week for cisplatin, p<0.001). Conclusions: SP3 was noninferior and superior to SP5 in terms of PFS and ORR. However, considering the small benefit in PFS and no difference in OS, both SP3 and SP5 can be recommended for the first-line treatment of AGC. Clinical trial information: NCT00915382.

Evaluation of serum HER2 extracellular domain in in metastatic gastric or gastroesophageal junction cancer: Correlation with HER2 status by immunohistochemistry and fluorescence in situ hybridization and clinicopathologic parameters.

4107 Background: To explore the association between serum human epidermal growth factor receptor-2 (HER2) extracellular domain (ECD) and tissue HER2 status, their relationship with clinicopathological parameters and impact on overall survival (OS) in metastatic gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. Methods: A total of 219 histologically confirmed inoperable locally advanced, recurrent, or metastatic gastric or GEJ adenocarcinoma were included. Serum HER2 ECD was measured by chemiluminescent assay. Tissue HER2 status was accessed by fluorescent in situ hybridization (FISH) and immunohistochemistry (IHC) assay. Results: The median serum ECD level was 9.3 ng/ml (range 3.0 to >350). Tissue HER2 status was positive (IHC3+ or 2+ with FISH amplification) in 37 patients (16.9%) and negative in 182 patients (83.1%). Statistically significant associations were found between serum HER2 ECD level and HER2 status assessed by IHC and FISH. The ROC-analysis suggested the cutoff of 16.35 ng/ml (24 of 219 patients had HER2 ECD >16.35 ng/ml ) could produce a sensitivity of 51.4% and a specificity of 97.3% to predict tissue HER2 status. If the cutoff value was increaseed to 22 ng/ml, then all 12 patients with serum HER2 ECD >22 ng/ml were HER 2 positive in primary tumor, corresponding to a specificity of 100% and a sensitivity of 32.4%. High serum HER2 ECD levels were strongly associated with liver metastasis (P < 0.001), the intestinal histologic type (Lauren's classification) (P =0.003), large number of metastais (>2) (P=0.012) and increased LDH level (P < 0.001) . High serum HER2 ECD levels were more common in GEJ adenocarcinoma although the difference had no stastical significance. HER2 ECD levels did not show a significant impact on OS. Conclusions: A significant association was observed between serum HER2 ECD levels and tissue HER2 status in metastasis gastric or GEJ adenocarcinoma. The high specificity of serum HER2 ECD assay to predict tissue HER2 status suggests its potential use as a surrogate marker of the HER2 status in gastric cancer.

Role of intervention for biliary and gastric/intestinal obstruction in gastric cancer with peritoneal metastasis

Gastrointestinal (GI) luminal obstruction or malignant biliary obstruction (MBO) is not a rare condition in gastric cancer patients with peritoneal metastasis. The role of endoscopic or percutaneous interventions is not fully elucidated in this setting. A total of 123 patients with unresectable or recurrent gastric adenocarcinoma with peritoneal metastasis receiving intravenous and intraperitoneal paclitaxel combined with S-1 were retrospectively studied. Safety and efficacy of interventions for GI luminal obstruction and MBO were evaluated. A total of 27 patients (22%) underwent GI luminal and/or biliary interventions; GI luminal alone in 10, biliary alone in 10 and both in seven, with a technical success rate of 100%. Clinical success rate was 65% in self-expandable metallic stents (SEMS) placement for GI luminal obstruction. Eastern Cooperative Oncology Group (ECOG) performance status (PS) was prognostic of clinical success in GI luminal stenting (100% in PS of 1 vs 14% in PS of 2-3, P < 0.001). Biliary drainage (endoscopic SEMS placement in four and percutaneous transhepatic biliary drainage in 12) relieved obstructive jaundice in 94%. Six complications were observed: four after GI luminal stenting (two occlusion and one aspiration pneumonia) and two after biliary stenting (one cholangitis and one cholecystitis). Median survival after the initial intervention was 5.7 months. PS at interventions was prognostic of survival after interventions (12.3 months in PS of 1 vs 2.2 months in PS of 2 or 3, P < 0.001). Endoscopic or percutaneous interventions for GI luminal obstruction or MBO were feasible and effective in gastric cancer patients with peritoneal dissemination receiving combination chemotherapy.

Combination of low-dose docetaxel and standard-dose S-1 for the treatment of advanced gastric cancer: efficacy, toxicity, and potential predictive factor

The aim of this study was to evaluate the efficacy and toxicity of low dose of docetaxel in combination with standard dose of S-1 for patients with advanced or recurrent gastric cancer and to investigate whether the protein expression level of dihydropyrimidine dehydrogenase is a predictive factor of toxicities or responses. Between March 2010 and December 2011, 61 patients from the Department of Medical Oncology of Shanghai Zhong Shan Hospital, Fudan University, were enrolled in the study. Patients with advanced or recurrent gastric adenocarcinoma were treated with docetaxel of 40 mg/m(2) intravenously on day 1 and S-1 of 80 mg/m(2) orally on days 1-14 every 3 weeks as first-line chemotherapy. The chemotherapeutic effects were evaluated following every 3 cycles of chemotherapy using the Response Evaluation Criteria In Solid Tumors (RECIST). The serum of peripheral blood was obtained at the start of the study and at each evaluation point to analyze the protein expression level of DPD, which was estimated using an enzyme-linked immunosorbent assay. All the patients were followed-up until the time of progression, death, or the censor time, to calculate progression-free survival and overall survival (OS) time. In total, 61 patients [median age 60 years (range 28-76 years)] received a total of 318 treatment cycles [median 5 (range 2-9)], and 94 cycles of single S-1 maintenance treatment. One complete response (CR) and 25 partial responses (PR) were observed, with an overall response rate of 42.6%. A total of 29 patients (47.5%) had stable disease (SD) and 6 patients (9.8%) had progressive disease (PD). The disease control rate (DCR, CR + PR + SD) was 90.2%. Median overall survival was 13.0 months [95% confidence interval (CI) 10.76-15.24 months], and median PFS was 6.0 months (95% CI 4.61-7.39 months). Progression-free survival was far longer in peritoneal metastatic patients than that in patients with other metastases (7.3 ± 2. 6 vs. 5.4 ± 2.8 months; P < 0.05); however, this was not the case for OS. Grade 3-4 neutropenia was well controlled and grade 4 non-hematologic toxicities did not occur. Baseline expression level of DPD was not associated with efficacy. Lower expression level of DPD was correlated with high grade of toxicities (P < 0.05). This combination of standard dose of S-1 and low dose of docetaxel is effective and well tolerated in patients with advanced or recurrent gastric cancer. Peritoneal metastasis is treated more effectively by this regimen than other forms of metastases. Baseline DPD expression level in the serum is associated with toxicity, but not tumor response.

18F-FDG PET-CT for detecting recurrent gastric adenocarcinoma

To evaluate the utility of fluorine-18 fluorodeoxyglucose (18F-FDG) PET-CT in the diagnosis of recurrent gastric adenocarcinoma in a Non-Oriental Asian population. In this retrospective analysis, data from 72 Non-Oriental Asian patients, who underwent 93 18F-FDG PET-CT studies, were evaluated. All patients had histopathologically proven gastric adenocarcinoma, for which they had undergone primary treatment. PET-CT was performed for suspected recurrence or for post-therapy surveillance. PET-CT findings were analysed on a per-patient and per-region basis (local/lymph node/liver/lung/bone/others). A combination of clinical follow-up (minimum 6 months; range: 6-36 months), imaging follow-up and/or histopathology (when available) was taken as the reference standard. Sensitivity, specificity and predictive values were calculated for PET-CT on both a per-study and per-lesion basis. The mean patient age was 52.8 ± 11.8 years (male/female: 52/20). Out of 93 PET-CT studies, 56 (60.2%) were positive and 37 (39.8%) were negative for recurrent disease. On per-study-based analysis, 18F-FDG PET-CT has a sensitivity, specificity and accuracy of 95.9, 79.5 and 88.1%, respectively. The accuracy of 18F-FDG PET-CT was 89.2% for local recurrence, 94.6% for lymph nodes, 96.7% for liver, 96.7% for lung, 98.9% for bone and 98.9% for other sites. The accuracy of 18F-FDG PET-CT was lower for local recurrence as compared with that for liver (P=0.012) and bone (P=0.012). No significant difference was found in the diagnostic accuracies for other regions. 18F-FDG PET-CT is highly sensitive and specific for detecting recurrence in patients with gastric adenocarcinoma. It shows high accuracy both on a per-patient and per-lesion basis.

A prognostic model in patients who receive chemotherapy for metastatic or recurrent gastric cancer: validation and comparison with previous models

To make up for the limitations of previous prognostic models, we developed and validated a model in patients with metastatic or recurrent gastric adenocarcinoma (AGC), and to compare with previous models. A total of 2,805 patients received chemotherapy for AGC in Asan Medical Center between January 2000 and December 2008 and were randomly split into training and validation sets of 1,870 and 935 patients, respectively. A prognostic model was developed from the training set. The median follow-up duration was 26.5months (range, 10.8-116.3), during which time 2,495 patients (88.9%) died. Eight factors associated with poor prognosis were identified by multivariate analysis: ECOG performance status ≥2 (2 points), no gastrectomy, peritoneal metastasis, bone metastasis (2 points), lung metastasis, alkaline phosphatase>120IU/l, albumin<3.3g/dL, and total bilirubin>1.2mg/dL. A prognostic model was developed by dividing patients into good (0-1 points), moderate (2-3), and poor (≥4) risk groups. The overall survival (OS) curves for three risk groups differed significantly for both the training and the validation sets (P<0.001 each). In the training set, the median OS for the three risk groups was 14.0, 9.4, and 5.1months, respectively. Application of three previous prognostic models to our validation set showed that the four models, including ours, had similar ability to predict survival outcomes (c-statistics, 0.5520-0.5836). Validation and comparison of prognostic models indicated that our model was as effective as the previous models to stratify the patients with AGC.

The efficacy and toxicity of modified docetaxel, cisplatin and 5-fluorouracil combination therapy for 27 patients with advanced stage gastric adenocarcinoma

Objective The aim of this study was to evaluate the efficacy and toxicity of modified docetaxel, cisplatin and calcium folinate (CF)/5-fluorouracil (mDCF) combination therapy for 27 patients with recurrent or metastatic gastric adenocarcinoma (R/MGC).

A randomized phase II trial of irinotecan plus oxaliplatin versus oxaliplatin, fluorouracil (5 FU), leukovorin (LV) as first-line treatment in advanced gastric cancer

4536 Background: To compare the efficacy and tolerance of two oxaliplatin-based regimens as first-line treatment of advanced gastric cancer. Methods: Chemotherapy-naïve patients with measurable recurrent or metastatic gastric adenocarcinoma, PS (ECOG) 0–2 and adequate organ functions were randomly assigned to receive either irinotecan 200mg/m2 and oxaliplatin 80mg/m2 (IO), every 21 days or oxaliplatin 85mg/m2 on day 1, 5-FU 400 mg/m2 (over 1 hour infusion) + 600mg/m2 (over 22 hours infusion) on days 1 and 2, leucovorin (LV) 200mg/m2 on days 1 and 2 (FOLFOX4) every 2 weeks. Study endpoints: Overall Response Rate (ORR), Toxicity Time to Progression (TTP) and Survival (S). Results: 138 patients were enrolled and all were evaluable for response. Median number of cycles administered was 5.5 (range 1–10) for IO and 7 (range 1–18) for FOLFOX4. In an intent-to treat analysis the ORR (RR+CR) was 29.4% for IO arm and 34.3 % for FOLFOX4 arm (p= 0.587). The median response duration was 5.63 months (mo) for IO arm and 6,6mo for FOLFOX4 arm. Median TTP was 4.2mo and 6,1mo for IO and FOLFOX4 arm respectively (p= 0.012). Median OS was 9.4mo for IO and 11.97mo for FOLFOX4 (p= 0.456). Toxicity was acceptable, with one toxic death in each arm. Grade 3–4 vomiting (7.3%), diarrhea (11.8%), neutropenia (22%) and febrile neutropenia (5.9%) occurred more frequently in IO arm, while anaemia (4.3%) and grade II neurotoxicity (11.4%) was more frequent in FOLFOX4 arm. Conclusions: Both regimens are well tolerated and active in advanced gastric cancer. Based on the TTP and toxicity profile, the FOLFOX4 regimen merits to be further evaluated in prospective phase III trials. No significant financial relationships to disclose.

Oxaliplatin Combined with Continuous Infusion of 5-Fluorouracil as First-Line Chemotherapy in Patients with Metastatic or Recurrent Gastric Adenocarcinoma

Background: The aim of this clinical study was to evaluate the efficacy of combination chemotherapy of oxaliplatin, leucovorin and continuous-infusion 5-fluorouracil (5-FU) for advanced gastric cancer. Methods: Patients with previously untreated gastric cancer with measurable disease received oxaliplatin (100 mg/m², day 1), followed by leucovorin (100 mg/m², day 1) and 5-FU (2,400 mg/m², days 1–2), which was repeated every 2 weeks. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS) and toxicity. Results: Forty-eight patients were enrolled, and 45 were evaluable for response. A total of 320 cycles of chemotherapy were administered (median 6 cycles per patient). One complete response (2.1%) and 19 partial responses (39.6%) were noted, resulting in an ORR of 41.7% (95% confidence interval, CI: 27.7–55.6%) by intent-to-treat analysis. With a median follow-up duration of 22 months, the median PFS was 5.3 (95% CI: 2.8–7.8) months and the median OS was 13.6 (95% CI: 9.3–17.9) months. There was 1 treatment-related death, and the most common grade 3/4 toxicity was neutropenia (36.1%). Three patients discontinued treatment because of serum creatinine elevation. Conclusion: This study reaffirms the efficacy of oxaliplatin in advanced gastric cancer, but its dose of 100 mg/m² remains to be reconsidered in Korean patients.

A phase I study of palliative chemoradiation therapy with paclitaxel and cisplatin for local symptoms due to an unresectable primary advanced or locally recurrent gastric adenocarcinoma

To establish the maximum tolerated dose and dose-limiting toxicity of chemoradiation with paclitaxel (PTX) and cisplatin (CDDP) for patients with local symptoms due to unresectable primary advanced or locally recurrent gastric adenocarcinoma located at left-upper abdomen. Chemotherapy consisted of PTX at escalating doses of 40-80 mg/m(2) per day and CDDP at escalating doses of 20-25 mg/m(2) per day on days 1, 15, and 29. Concurrent radiation was administered up to a dose of 45 Gy for 5 weeks. A total of nine patients were enrolled, of which six were into level 1 (PTX 60 mg/m(2) and CDDP 20 mg/m(2)) and three into level -1 (PTX 50 mg/m(2) and CDDP 20 mg/m(2)). At level 1, one patient developed grade 3 fatigue, and the other experienced grade 5 DIC, grade 5 pneumonia, grade 4 thrombocytopenia, grade 3 hyponatremia, and grade 3 esophagitis as dose-limiting toxicities. A palliative effect was observed in eight of nine patients; six of six patients at level 1 and two of three at level -1. PTX 50 mg/m(2) and CDDP 20 mg/m(2) given biweekly with concurrent radiation therapy of 45 Gy were well tolerated.

Paraneoplastic fasciitis–panniculitis syndrome: a neurological point of view

A 54-year-old woman who had undergone gastrectomy to treat gastric adenocarcinoma 5 years previously and had since been in remission presented to a neuromuscular clinic complaining of stiffening and painful spasms of the legs and abdomen. Repeat pan-CT scans and gastric biopsy confirmed the recurrence of poorly differentiated signet ring gastric adenocarcinoma. Her symptoms improved remarkably on initiation of chemotherapy and worsened on discontinuation of chemotherapy. Neurological examination, MRI of the abdomen and lower extremities, whole-body fluorodeoxyglucose PET, pan-CT scan, electromyography, muscle biopsy, upper gastrointestinal tract radiography, esophagogastroduodenoscopy, and immunophenotyping (paraneoplastic, rheumatological and autoimmune diseases panels). Paraneoplastic fasciitis-panniculitis syndrome associated with the recurrence of poorly differentiated signet ring gastric adenocarcinoma. Chemotherapy of recurrent gastric adenocarcinoma and symptomatic management of painful spasms.

Gastric Remnant Adenocarcinoma with Micropapillary Component

An invasive micropapillary carcinoma (IMPC) is defined as a carcinoma composed of small clusters of tumor cells lying within clear spaces simulating vascular channels [1]. It is a histological variant of invasive breast carcinoma with poor clinical prognosis [2, 3]. This distinct histological pattern has been described in various organs, including the urinary bladder, lung, ovary, and major salivary glands [4-8]. Although rarely observed as a pure histological component, IMPC is usually mixed with otherwise conventional carcinoma [3] and is therefore often referred to as carcinoma with a micropapillary component. In cases of adenocarcinoma with a micropapillary component, an abrupt transition is usually seen between the invasive micropapillary component and conventional adenocarcinoma [3]. IMPCs are all invariably associated with high aggressiveness, extensive lymphovascular invasion, extensive lymph node metastases, and poor prognosis [1-3]. We describe the first case of primary IMPC originating in the stomach as a histologic subcomponent of recurrent gastric adenocarcinoma.

Randomized phase III study of 5-fluorouracil (5-FU) alone versus combination of irinotecan and cisplatin (CP) versus S-1 alone in advanced gastric cancer (JCOG9912)

LBA4513 Backgrounds: We conducted a 3-arm phase III study to investigate superiority of CP and non-inferiority of S-1 to 5-FU for advanced gastric cancer in the primary endpoint of overall survival (OS) and secondary endpoints of response rate (RR), time to treatment failure (TTF), non-hospitalized survival (NHS) and toxicities. Methods: Treatments with 5-FU (800mg/m2/d, ci, d1–5, q4w), CP (irinotecan, 70mg/m2, div, d1&amp;15 and cisplatin, 80mg/m2, div, d1, q4w) and S-1 (40mg/m2, b.i.d., d1- 28, q6w) were continued until disease progression or unacceptable toxicities. Tumors were evaluated every two months. With 230 patients (pts) per arm, this study had 80% power to demonstrate 10% superiority of CP and non-inferiority with 5% margin (hazard ratio, HR=1.16) of S-1 and 0.05 study-wise 1-sided alpha. Results: 704 pts having unresectable or recurrent gastric adenocarcinoma with/without target lesions (TL) were randomized between Nov 2000 and Jan 2006. Final analysis was performed in Feb 2007 when 601 pts (85%) were dead. The results of OS are shown in Table . Median TTF/NHS were 2.3M/7.2M for 5-FU, 3.7M/9.5M for CP, and 4.0M/9.2M for S-1. Incidences (%) of grade 4 neutropenia, grade ≥3 febrile neutropenia, infection with neutropenia, anorexia, diarrhea within 6M, and treatment related death (5- FU/CP/S-1) were 0/37/0, 0/9/0, 0/8/0, 13/33/12, 0/9/8, and 0/1.3/0.4. In the subset having TL, RRs of 5-FU/CP/S-1 (n=175/181/175) were 9%/38%/28%, and their median survival times (MST) were 9.0M/12.1M/10.5M and HRs to 5-FU were 0.78 (95%CI, 0.63–0.98) for CP and 0.85 (0.68–1.06) for S-1. In the subset not having TL, the MSTs of 5-FU/CP/S-1 (n=59/55/59) were 13.5M/14.4M/18.1M and HRs were 1.02 (0.68–1.55) for CP and 0.82 (0.55–1.24) for S-1. Conclusions: S-1 showed a significant non-inferiority to 5-FU. Although CP did not show statistically significant superiority to 5-FU in all pts, it may have a benefit for some subgroups such as pts with measurable metastatic diseases. [Table: see text] [Table: see text]

Esophagoenteral stents in patients with recurrent gastric adenocarcinoma

One of the problems that can appear in patients with total gastrectomy for adenocarcinoma with esophagoenteral anastomosis is the appearance of a stenosis of the anastomosis. These stenosis are frequently malignant due to relapse of neoplasia. The therapeutic possibilities available are the surgical bypass or palliative treatment. There is very little experience described in the literature (21 cases) on the placing of self-expandable metal stents as a palliative treatment for the symptoms of stenosis.We present our experience of 3 patients, in whom 4 esophageal stents were fitted (1 covered and 3 uncovered) with good results. The dysphagia disappeared or improved, it allowed the ingestion of a soft diet and meant an improvement in the quality of life and at the same time stopped the weight loss. It seems an effective palliative treatment as a treatment for dysphagia in patients with tumoral relapse in the anastomosis of total gastrectomies.