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e14587Background: We conducted a multicenter phase II study using peptide vaccine cocktail named OCV-C01 containing epitope peptides derived from KIF20A, VEGFR1, and VEGFR2 combined with gemcitabin...

48 Background: Accurate assessment of human epidermal growth factor receptor (HER) 2 is essential for patients with gastric cancer (GC) who may benefit from therapies targeting this surface receptor such as trastuzumab. The extracellular domain (ECD) of the HER2 protein may be shed into the serum and is detectable using an enzyme-linked immunosorbent assay. Correlations have been reported between raised baseline ECD levels, suggesting that serum ECD levels may be useful in making treatment decisions in patients with HER2 positive GC. We investigated this relationship in patients with resectable GC. Methods: This retrospective study was conducted in 71 patients with resectable GC between Apr. 2009 and May 2012. We assessed HER2 protein overexpression and gene amplification using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH). HER2 positive was defined as IHC 3+ or IHC 2+/ positive FISH. The serum HER2-ECD level was measured using the blood serum before the surgical treatment. We examined the relationship between serum HER2-ECD level, HER2 expression in resected specimens, depth of invasion of cancer, lymph node metastasis, and clinical stage. Results: Baseline values were available in 71 patients, and of these, 2 (2.8%) had raised levels (> 15 ng/mL). Median serum ECD levels was 11.7 (7.5-17.9) ng/mL. Two patients showing high HER2-ECD without HER2 over-expression. No clear relationship was found between baseline ECD levels and HER2 over-expression. Serum HER2-ECD level was not associated with invasion depth and lymph node metastasis, and clinical stage. Conclusions: There is no significance of serum HER2-ECD testing in resectable gastric cancer.

263 Background: Gemcitabine (Gem) monotherapy or Gem-based combination therapy is a standard first-line therapy for advanced pancreatic cancer (PC). There is no consensus on second-line therapy in patients (pts) with disease progression (PD) after Gem-based therapy. S-1, an oral fluoropyrimidine derivative, is commonly used for the second-line treatment of PC in Japan. Shitara et al previously reported that IRIS regimen showed that 44% of response rate (RR), 4.9 mo of median progression free survival (PFS), and 11.3 mo of median overall survival (OS), respectively. Therefore a randomized phase II trial was conducted to evaluate the efficacy and safety of IRIS compared with S-1 alone in the second-line setting. Methods: The inclusion criteria were as follows: (1) histologically or cytologically proven pancreatic adenocarcinoma or adenosquamous carcinoma; (2) confirmed PD after Gem treatment; (3) ECOG PS, 0-1; (4) measurable metastatic lesion based on RECIST criteria; (5) age ≥ 20 years; (6) total bilirubin < 2.0 mg/dL. Patients were randomized to receive either IRIS (CPT-11 100 mg/m2, iv, d1,15 plus S-1 80/100/120 mg/day based on BSA, po, d1-14, q4w; Arm A) or S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w; Arm B). The primary endpoint was to compare PFS in Arm A and Arm B. Results: Of a total of 137 pts enrolled between Nov 2008 and Mar 2011, 127 were eligible (60 randomized to Arm A and 67 to B). Median PFS in Arm A and B was 107 and 58 days, respectively (HR= 0.767; 95% CI, 0.527-1.114; p=0.1750). Median OS in Arm A and B was 208 and 176 days, respectively (HR=0.749; 95% CI, 0.512-1.093; p=0.1338). RR was 18.3% in Arm A (11/60; 95% CI, 9.5-30.4) and 6.0% in Arm B (4/67; 95% CI, 1.7-14.6)(p=0.0311). The incidences of grade 3/4 toxicities were as follows: neutropenia (15.6% and 4.3%), anorexia (23.4% and 17.3%), nausea (6.3% and 2.9%), and diarrhea (3.1% and 2.9%) in Arm A and B, respectively. Both regimens were tolerable. Conclusions: Although IRIS showed no significant improvement in PFS or OS compared with S-1 alone in this study, it showed significant advantage in RR, and favorable HR in both of PFS and OS. IRIS might have potential power to treat second-line PC patients. Further study is warranted. Clinical trial information: JapicCTI-080657.

223 Background: Gemcitabine is a key drug for treating pancreatic cancer; however, with the limitation in clinical benefits, the development of another potent therapeutic was strongly called for. VEGF-receptor 2 (VEGFR2: Flk-1 and KDR) is an essential target for tumor angiogenesis, and we have executed a phase I clinical trial using gemcitabine and VEGFR2-peptide (Cancer Sci 2010). Based on promising phase I trial results, a multicenter, randomized, placebo-controlled, double-blind phase II/III clinical trial has been conducted (UMIN000001664). Methods: The eligibility criteria are: locally advanced, metastatic, or unresectable pancreatic cancer. Patients were allocated to either VEGFR2 peptide (OTS102) + gemcitabine group or placebo + gemcitabine in 2:1 ratio by dynamic allocation method. The primary endpoint was overall survival. The Harrington-Fleming test, with the weight proportional to cumulative death probability, was used for the statistical analysis under the time-lagged effect of immunotherapy. Sample size was estimated presuming the effects will be observed from the time point of 50% cumulative survival rate. Assuming a type I error alpha (two-sided) level of 5% and a power of 80% or more for 50%-60% reduction of hazard, sample size necessary was estimated as 100 patients for the active group and 50 patients for the placebo group. Results: No statistically significant survival time prolongation was observed in OTS102 add-on group (p = 0.92). However, the three-month landmark analysis revealed significant interaction between the treatment and reports of indurations or ulcerations (p = 0.005) in add-on group, and if patients survived for over three months, grade 1-2 patients had better survival than grade 0 (1-year survival: 47%(23/49) and 22%(9/44), respectively) in add-on group. Conclusions: Despite the lack of survival time prolongation by OTS102 add-on to gemcitabine therapy, patients experienced injection site indurations or ulcerations may have better survival, suggesting new prognostic factors for VEGFR2-epitope peptide. Our results indicate the possibility of epitope peptide used in cocktail therapies. Clinical trial information: UMIN000001664.

4035 Background: The GEST study (Ioka et al. ASCO 2011, Abstract 4007) demonstrated the non-inferiority of S-1 to GEM with respect to the primary endpoint of overall survival (OS) in patients with pancreatic cancer (PC). We now report the updated results of this study. Methods: The GEST study was a randomized, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG Performance status (PS) of 0-1, and adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w), or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was OS, used to assess the non-inferiority of S-1 and the superiority of GS to GEM. Patient information was updated in July 2011. Results: At the time of this follow-up analysis, median follow-up was 29.8 months with 795 OS events, compared with 18.4 months with 710 OS events out of 832 patients at the previous analysis. Median OS was 8.8 months (95% CI: 8.0–9.7) in the GEM group and 9.7 months (95% CI: 7.6-10.8) in the S-1 group (HR=0.96, 97.5% CI: 0.79-1.17, p

381 Background: SU is an oral, multitargeted, antiangiogenic, tyrosine kinase inhibitor effective in patients (pts) with unresectable, well-differentiated pancreatic NET. This open-label, phase II study examined whether SU is also effective in Japanese pts with this disease. Methods: Japanese pts received SU 37.5 mg/day on a continuous daily dosing (CDD) schedule (28-day cycle). The primary endpoint was clinical benefit rate (CBR; complete response [CR] + partial response [PR] + stable disease [SD] ≥24 weeks). Secondary endpoints included: objective response rate (ORR; CR + PR), 6-mos progression-free survival (PFS) probability, safety and pharmacokinetics. Tumor assessments were performed at baseline and 8-wk intervals by CT or MRI (RECIST). Results: Twelve patients were enrolled and received treatment (tx; median age 54 yrs, range 34–79); 9 were ongoing at data cut-off (July 1, 2011). CBR was 75.0% (95% CI 42.8, 94.5), comprising 5 PRs and 4 pts with SD ≥24 weeks. ORR was 41.7% (95% CI 15.2, 72.3). 6-mos PFS probability was 91.7% (95% CI 53.9, 98.8). One PR occurred in a pt with gastrinoma, in whom gastrin levels decreased by 93% and tumor bulk decreased by 45%. All-causality, any-grade (G) AEs included diarrhea (n=9, 75%), HFS and hypertension (both n=8, 67%). Neutropenia was the most common G3 AE (n=5, 42%, all tx-related). Three pts (25%) experienced G4 AEs (herpes encephalitis, convulsion, loss of consciousness [n=1] and lipase increased [n=2], all tx-related).Two pts (17%) experienced serious AEs: convulsion and loss of consciousness (n=1, tx-related), and acute cholecystitis (n=1, unrelated to tx). There were no deaths on study; one death due to disease progression occurred 3 mos after study withdrawal. On day 15 (cycle 1), mean trough plasma concentrations (n=10) for SU, its metabolite, and SU + metabolite were 53.9, 23.7 and 77.5 ng/mL, respectively. SU on a CDD schedule resulted in sustained drug concentrations without accumulation across cycles. Conclusions: SU 37.5 mg/day on a CDD schedule demonstrated antitumor activity in Japanese pts with unresectable, well-differentiated pancreatic NET. Common AEs were consistent with the known safety profile of SU.

4007 Background: S-1, an oral fluoropyrimidine, is one of the key drugs for PC in Japan. Phase II studies of S-1 alone as well as those of GS have shown high efficacy against the tumor as the first-line treatment of metastatic PC. Methods: The GEST study was a randomized, prospective, open-label, 3-arm, phase III study. Chemotherapy-naive patients with unresectable advanced PC, an ECOG PS of 0-1, with adequate organ functions were randomly assigned to receive GEM (1000 mg/m2, iv, d1, 8 and 15, q4w), S-1 (80/100/120 mg/day based on BSA, po, d1-28, q6w) or GS (GEM 1000 mg/m2, iv, d1 and 8 plus S-1 60/80/100 mg/day based on BSA po, d1-14, q3w). The primary endpoint was overall survival (OS) to assess the non-inferiority of S-1 alone and the superiority of GS to GEM, with a 90% power and a 1-sided alpha value of 0.0125 for each multiplicity-adjusted comparison. Secondary endpoints were progression-free survival (PFS), response rate (RR), safety, and quality of life (EQ-5D). Results: A total of 834 patients we...

4058 Background: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiotherapy for locally advanced pancreatic cancer (PC). Methods: Locally advanced PC patient...

e15680 Background: Radiological examinations including computed tomography (CT) and endoscopic ultrasound sonography (EUS) are important for the diagnosis of pancreatic neuroendocrine tumors (PNETs). Pathological diagnosis is not needed with functional PNETs because the diagnosis is made by biochemical testing. Therefore, pathological diagnosis is essential for the non-functional PNETs (nf-PNETs). In this study, we examined the diagnostic yield of radiological examinations and endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) for nf-PNETs. Methods: From January 1997 to December 2007, consecutive 38 cases were pathologically diagnosed from as nf-PNETs at Aichi Cancer Center Hospital. Of these 33 patients was diagnosed with surgical specimen, 5 patients with EUS-FNA specimen. Of 33 patients, 16 patients underwent EUS-FNA preoperatively, and were examined further: their EUS-FNA specimens were submitted for additional immunohistochemical examination for CD 56, chromogranin A, synaptophysin, somatostatin receptor 2A (SSTR2A) and Ki-67 using cell block method. Staging of PNETs was performed according to WHO classification. Results: 16 patients (10 men and 6 women) who ranged in age from 23 to 81 years. The mean of tumor size was 2.2 cm and ranged from 0.7 to 4.4 cm. Diagnosis by CT and EUS was 12 (75.0%) PNETs, two pancreatic cancer, one solid papillary tumors and one malignant lymphoma. Accurate diagnosis by cytology and immunohistochemistry was 75.0% and 93.8%, respectively. The Ki-67 in specimens of malignancy tended to be higher than those of benign or uncertain behavior. If we assumed that a tumor with Ki-67 of more than 2% was malignancy, the diagnostic accuracy was 75.0%. Positive reaction to SSTR2A was up to 14 out of 16 nf-PNETs. Conclusions: The EUS-FNA is a useful tool for diagnosing nf-PNETs with immunohistochemical staining compared to cytology and radiological examinations. Ki-67 may be also effective to predict the degree of malignancy. No significant financial relationships to disclose.

e15631 Background: Gastric Submucosal tumors (SMTs) were incidentally discovered esophagogastroduodenoscopy (EGD). However, they have not been studied in detail of epidemiology. Furthermore, no treatment strategy for SMTs has been established with few studies looking into long-term outcomes. The aim of this study is to clarify the clinical features and long-term outcomes of gastric SMT at a single institute for 10-year period. Methods: We performed a total of 5307 EGDs and detected 188 gastric SMTs during 1998. All clinical data including incidence, size and location in stomach were analyzed for the medical records. A retrospective review was conducted for 10-year period for 109 patients and 79 patients were excluded because of simultaneous surgery (3), disappear in follow- up EGD (27), lost of follow-up (49). Results: Gastric SMTs were detected 188 (81 males, 107 females) of 5307 patients (3.5%). Majority size of SMTs was less than 1cm (64%) and SMTs No significant financial relationships to disclose.

4574 Background: Submucosal lesions are incidentally detected on barium meal study or endoscopy. The differential diagnosis of them includes a variety of neoplasms, inflammation, and extraluminal c...

4550 Background: As shown in our previous phase I study (Oncology 2005, 69:421–427), gemcitabine and S-1 combination therapy (GS therapy) appears to be feasible and effective against advanced pancreatic cancer. The present multicenter phase II study was conducted to confirm the efficacy and toxicity of GS therapy for metastatic pancreatic cancer. Methods: Patients with histologically or cytologically proven pancreatic adenocarcinoma with at least one measurable metastatic lesion were eligible for the study. Other eligibility criteria included: no previous treatment for pancreatic cancer except surgery, age =20 and =74 years, ECOG performance status of 0 or 1, and adequate organ function. Gemcitabine was given intravenously at a dose of 1,000 mg/m2 over 30 min on days 1 and 8, and S-1 was given orally at a dose of 40 mg/m2 twice daily from day 1 to day 14, repeated every 3 weeks. The objective response rate was assessed according to RECIST. Results: A total of 55 patients from 10 institutions were enrolled between October 2004 and July 2005. The efficacy and toxicity were analyzed in 54 patients who received at least one course of GS therapy. The median number of treatment courses was 7 (range, 1–24+). Although no complete response was seen, a partial response was achieved in 24 patients, resulting in an overall response rate of 44% (95% CI, 30.9–58.6%). Twenty-six patients (48%) had stable disease. The median progression-free survival was 5.9 months (95% CI, 4.1–6.9 months) and the median overall survival was 10.1 months (95% CI, 8.5–10.8 months) with a 1-year survival rate of 33%. The major grade 3–4 toxicities were neutropenia (80%), leucopenia (59%), thrombocytopenia (22%), anorexia (17%), rash (7%), nausea (6%) and fatigue (6%). Hematological toxicity was mostly transient and there was only one episode of infection with grade 3–4 neutropenia. No treatment-related deaths occurred during the study. Conclusions: GS therapy produced a high response rate and good survival associated with an acceptable toxicity profile in patients with metastatic pancreatic cancer. A randomized phase III trial to confirm the efficacy of GS therapy is planned. No significant financial relationships to disclose.

15063 Background: Pancreatic cancer (PC) shows the worst mortality rate in common malignancies, with 5-year survival rate of 4%. The only way to cure the disease is surgical resection of early stage PC. Establishment of a screening strategy to detect early stage PC is eagerly expected. REG4, a member of the regenerating islet-derived (REG) family, are secreted proteins that play a role in tissue regeneration and inflammation in digestive organs. We reported overexpression of REG4 in PC cells and serum, and preliminary data of the serum REG4 level of pancreatic disease patients including PC patients. We conducted a prospective study to evaluate the role of serum REG4 in PC. Methods: The series included 57 patients diagnosed pathologically as PC between November 2004 and December 2005. Serum REG4 was quantified by standard sandwich ELISA (Enzyme Linked Immunosorbent Assay) using original kit (MBL116: provided by Medical and Biological Laboratories Co., LTD, Japan) before treatment. The upper limit of the test was set at 3.52ng/ml and was based on studies of serum from 48 healthy control subjects. Results: With a specificity of 100%, the diagnostic sensitivity and accuracy were 63.2% and 80.0%, respectively. The ROC (receiver operating characteristic) analysis showed that area under the curve was 0.91. REG4 levels were a significant differences between PC and control (p5.0ng/ml) and carbohydrate antigen19–9 (CA19–9>50U/ml) was 56.5% and 68.4%, respectively. No significant correlation was demonstrated between REG4 and CA19–9 (coefficient of correlation [rs]=0.45). Conclusions: This study shows the potential of serum REG4 as a screening test for PC, especially for early PC. REG4 is considered to be a more useful marker in combination with CA19- 9. No significant financial relationships to disclose.

19504 Background: Although imatinib is the most effective agent for metastatic gastrointestinal stromal tumors (GISTs), resistance to imatinib develops in most patients. While the effectiveness of an oral multitageted tyrosine kinase inhibitor for intolerant GIST is already reported, many of imatinib resistant patients are not available. We report clinical results of first imatinib and post imatinib treatment in a patient with metastatic or unresectable GIST. Methods: A retrospective review was undertaken in patients with metastatic or unresectable GIST treated with imatinib at Aichi Cancer Center Hospital between June 2001 and December 2005. Treatment schedule was four or six 100-mg capsules of imatinib orally once daily. Patients were evaluated for treatment, recurrence, and survival. Results: Forty-five patients (26 males and 43 metastatic patients) were treated with imatinib at first. The median age was 58 years (range 25–79). Primary tumor sites were as follow; stomach was 13, duodenum 9, small intestine except for duodenum 18, and colorectum 5. Metastatic sites were liver (21 patients), peritoneum (11 patients), both of them (10 patients), and the other (1 patient). The response rate (by RECIST) and PFS was 71.1% (32/45) and 24 months, respectively. Imatinib was well tolerated; only two patients stopped treatment due to nausea and vomiting. Twenty-six patients with disease progression were treated by the combination of many methods, and the following methods underwent as the second therapy; 9 patients underwent surgical resection, 7 patients underwent transarterial chemoembolization (TACE) for liver metastases, 9 patients enrolled in a clinical trial, and 9 patients continued imatininb because of clinical benefit and no other therapeutic options. PFS of surgery and TACE were 6 and 7 months, respectively. Out of 16 patients treated with surgery or TACE, 2 patients were well controlled by TACE more than 1 year. One patient, however, was suffering from intractable liver abscess after TACE. Conclusions: The efficacy and safety of imatinib for GIST is almost the same as in U.S. reports. TACE may be an effective treatment for liver metastases if new agents are not available. No significant financial relationships to disclose.

4159 Background: Standard chemotherapy for biliary tract cancer (BTC) has not yet established. This study retrospectively examined the results of non-surgical treatments in patients with advanced B...

4104 Background: The purpose of this study was to determine the efficacy and toxicity of S-1 in patients with metastatic pancreatic cancer. S-1, an oral anticancer agent, contains tegafur (FT: a pr...

4145 Background: Biliary tract cancer is one of the most malignant tumors, progresses in a short time period, and has a bleak prognosis. Moreover, early detection is difficult, and there is no stan...

4119 Background: Chemotherapy with gemcitabine(GEM) has been shown to be an effective agent in metastatic pancreatic cancer(MPC) with improvement of both quality of life and survival. While median ...

4078 Background: STI 571, (Gleevec), is a specific inhibitor of BCR-ABL, c-kit, and PDGFR tyrosine kinases. After demonstration of efficacy against KIT- positive GISTs, STI571 was approved for the treatment of GISTs in the US and the EU. This Phase II open-labelled, multicenter trial investigated the efficacy, tolerability, and PK of STI571 in Japanese pts with unresectable and/or metastatic malignant GISTs. Methods:The inclusion criteria were KIT-positive and unresectable and/or metastatic GISTs with measurable lesions, adequate organ function, PS (ECOG)of 0–2, and a life expectancy >2 months. Pts were randomized to either 400 or 600 mg/day of STI571. For PD, the dose was increased. Efficacy was assessed by SWOG criteria, and toxicity was reported by NCI-CTC v2.0. PK was examined in 21 patients. Results: 74 pts were enrolled (400 mg /600 mg = 28/46, M/F = 48/26, PS 0/1/2=57/14/3, median age=56 years (range 24–74)). C-kit mutations in exon 11 was the most common mutational abnormality (79.7 %) and mutatio...

4208 Background: Serum carbohydrate antigen 19–9(CA19–9) is one of the useful marker for diagnosis of pancreatic cancer (PC), but its value for evaluating the survival benefit with Gemcitabine(GEM)...