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Panitumumab and cetuximab are known to be effective treatments for KRAS wild-type metastatic colorectal cancer (mCRC). However, it remains unclear which of these two biologic agents confers the greatest benefit when combined with irinotecan in patients with KRAS wild-type mCRC previously treated with fluoropyrimidine, oxaliplatin and irinotecan.Data, from 139 patients who received panitumumab or cetuximab, in combination with irinotecan, for KRAS wild-type mCRC previously treated with fluoropyrimidine, oxaliplatin and irinotecan were analyzed. The efficacy and safety of panitumumab plus irinotecan was compared to that of cetuximab plus irinotecan.Baseline characteristics of the panitumumab plus irinotecan (n=42) and cetuximab plus irinotecan (n=97) groups were similar. Among patients with measurable lesions, the response rate was 34% in the panitumumab plus irinotecan group and 20% in the cetuximab plus irinotecan group. Median progression-free survival (PFS) was 4.3 and 5.7 months in the panitumumab and cetuximab groups, respectively. Median overall survival was 13.6 months with panitumumab and 11.2 months with cetuximab.Panitumumab plus irinotecan was well-tolerated and displayed a similar level of efficacy to that of cetuximab plus irinotecan.

Fibroblast growth factors and their receptors regulate key cellular functions, such as proliferation, differentiation and survival. Herein, we studied the prevalence and prognostic role of fibroblast growth factor receptor 2 (FGFR2) amplification in patients with advanced gastric cancer (AGC) who received systemic chemotherapy.The gene copy number of FGFR2 was investigated in 80 patients with AGC who received systemic chemotherapy. FGFR2 gene status was assessed by dual-color fluorescence in-situ hybridization.Among 80 patients, FGFR2 amplification was observed in seven cases (11.5%). Patients with FGFR2 amplification had significantly shorter overall survival (OS) than did those without FGFR2 amplification (9.1 vs. 16.5 months; p=0.037). In multivariate analysis, disease status and number of metastatic sites were associated with worse OS (p=0.015 and p=0.009, respectively). FGFR2 amplification tended to be correlated with a poorer outcome (p=0.080).FGFR2 amplification tended to result in a shorter survival period compared to cases without amplification.

The present study investigated whether bevacizumab (BV) is associated with postoperative wound complications (PWCs).We retrospectively analyzed patients undergoing surgery for liver metastases of colorectal cancer at our Institution. Patients were divided into 3 groups according to the preoperative treatment: che mo therapy with BV (group A), chemotherapy without BV (group B) and no chemotherapy (group C).Between February 2003 and September 2012, 297 patients underwent 373 surgeries. Groups A, B and C consisted of 23, 62 and 288 patients, respectively. PWCs occurred in 29 patients (7.8%). In multivariate analysis, there were no differences in PWCs among the groups (C vs. B:P=0.739; C vs. A: P=0.110). Conversely, lower serum albumin levels (3.5 g/dl vs. ≥ 3.5 g/dl: p=0.030) and synchronous colorectal resection (no vs. yes; p0.001) remained significant risk factors of developing PWCs.Chemotherapy with or without BV did not influence the risk of PWCs.

Typically, bevacizumab is initially infused for 90 min, then for 60 min, and subsequently for 30 min. The objective of the present study was to evaluate the safety profile of a short infusion of bevacizumab in Japanese colorectal cancer patients.The records of 58 patients who received bevacizumab (5 mg/kg) from June 2010 to September 2010 were reviewed. Bevacizumab was administered for 30 min at the first time. If patients had no infusion reaction, the infusion time was shortened to 10 min.None of the 58 patients who received bevacizumab experienced an infusion reaction (95% confidence interval 0-6.2). The only serious adverse event related to bevacizumab infusion was grade 3 proteinuria in 2 patients.Short infusion of bevacizumab for 30 min the first time and 10 min is safe and feasible.

The use of weekly paclitaxel (wPTX) has become a common practice as second-line chemotherapy in Japanese patients with advanced gastric cancer. The aim of the present study was to assess the efficacy of wPTX.We retrospectively analyzed data from 229 patients with advanced gastric cancer who received wPTX as second-line chemotherapy between March 2001 and January 2011 at our hospital. Patients received PTX at a dose of 80 mg/m(2) on days 1, 8, 15 of a 28-day cycle. Response and survival were evaluated.The overall response rate was 12.5% in 96 patients who had measurable lesions that were assessable for response. In 107 patients who had malignant ascites, the response rate for therapy of ascites was 38.3%. The median progression-free survival was 3.6 months, and the median overall survival was 6.3 months. Multivariate analysis revealed that the number of metastatic sites [hazard ratio (HR)=1.56, p=0.009], bone metastasis (HR=2.11, p=0.006), ascites (HR 1.75, p0.001), and the presence of the primary lesion (HR=1.77, p0.001) were independent prognostic factors of poor survival.wPTX is an effective regimen for advanced gastric cancer refractory to first-line chemotherapy.

Direct sequencing (DS) has often been used for detection of v-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations. High-resolution melting analysis (HRMA) is another method to detect mutations by using a light scanner, and is more rapid, lower in cost, and more sensitive than DS. We confirmed correspondence between DS and HRMA for KRAS mutation detection in colorectal cancer (CRC).From 102 patients with CRC, intended to receive cetuximab treatment at the National Cancer Center Hospital between September 2008 and July 2009, formalin-fixed paraffin-embedded tissues were retrospectively analyzed for KRAS status using HRMA and DS. Cetuximab efficacy was evaluated.Success rates of analysis by DS and HRMA were 100 out of the 102 patients (98.0%) and 99 out of the 102 patients (97.1%), respectively. The cases which failed by one method were analyzed by the other. KRAS mutant-type was detected by DS in 47 out of 100 samples (47.0%), and by HRMA in 45 out of 99 samples (45.5%). The concordance between the two methods was 94.8%. Forty-six out of the 53 patients with wild-type KRAS, as detected by DS received cetuximab and the response and disease control rates were 19.6% and 63.0%, respectively. With a median follow-up of 8.8 months, the median progression-free survival was 5.6 months and median overall survival was 11.1 months. The efficacy of two discordant cases which received cetuximab showed that the best responses were stable disease and progressive disease in one each, progression-free survival was 2.9 and 1.1 months and overall survival was 5.3 and 1.2 months, respectively.HRMA is a useful optional method for detection of KRAS mutations in CRC in light of accuracy, cost performance and rapidity.

The gene amplification of ribosomal protein S6 kinase 1 and 2 (S6K1 and S6K2) and its clinical relevance in gastric cancer remain unclear.A comparative genomic hybridization analysis and DNA copy number assay were performed for nine cancer cell lines. The gene amplification of S6K1 and S6K2 were determined using a DNA copy number assay of 213 gastric cancer tissues.S6K1 and S6K2 amplifications were observed in one and three cancer cell lines, respectively. No amplification of S6K1 was detected in the gastric cancer tissues, while S6K2 amplification was observed in 4.7% of the gastric carcinoma tissues. Patients with stage IV gastric cancer whose tumors exhibited amplification had a significantly shorter overall survival.S6K2 amplification was frequently observed in gastric cancer and was related to a poor prognosis. Our findings may provide novel insight into the dysregulation of mammalian target of rapamycin signaling by S6K2 amplification in gastric cancer.

Discontinuation of oxaliplatin-containing regimens is sometimes necessary due to hypersensitivity reactions for which effective countermeasures have not yet been identified.We retrospectively reviewed cases in which hypersensitivity reactions developed in 623 patients treated with oxaliplatin for colorectal cancer. Clinical outcomes of patients who underwent oxaliplatin rechallenge with rechallenge protocol (STEP 1: hydrocortisone, chlorpheniramine, and/or ranitidine; STEP 2: hydrocortisone with an escalating dose to 500 mg, and/or prolonged administration time of oxaliplatin; and STEP 3: STEP 2 plus a subcutaneous injection of epinephrine) were examined.Out of 623 patients, 126 (20.2%) patients developed hypersensitivity reactions. Out of these 126 patients, 99 (78.6%) underwent oxaliplatin rechallenge. As the initial oxaliplatin rechallenge, 19 patients received subsequent treatment without the rechallenge protocol and 80 patients received oxaliplatin with the rechallenge protocol of STEP 1 (n=64), STEP 2 (n=15), and STEP 3 (n=1). The median number of oxaliplatin rechallenges was 3 (range=1 to 29). The reason for treatment discontinuation was disease progression in 55 patients (56%) and hypersensitivity reactions in 21 patients (21%). Overall hypersensitivity reactions after rechallenge were observed in 59%, with grade 3/4 in 6%.The rechallenge protocol is an effective treatment option for patients with oxaliplatin hypersensitivity reactions.

A highly specific antibody against recombinant human dihydropyrimidine dehydrogenase (DPD) has been developed to immunohistochemically assess DPD expression in tumors. A new oral DPD inhibitory fluoropyrimidine (DIF), S-1, is reportedly effective against gastric scirrhous carcinoma.In this study, the relationship between immunoreactivity to DPD in biopsy specimens and the effects of chemotherapy were investigated in 61 patients treated with first-line fluoropyrimidine-based chemotherapy (S-1:DIF, 5-FU:non-DIF) for gastric scirrhous carcinoma.The response rate was significantly higher in patients with DPD-positive tumors than in those with DPD-negative tumors in the S-1 group (45.5%, 10.0%: p0.05), as compared to the 5-FU group (0%, 5.6%: p = 0.398). According to the median survival time, there was no significant difference between patients with DPD-positive tumors (364 days) and those with DPD-negative tumors (406 days; p = 0.626) in either the S-1 group or the 5-FU group (181 days and 256 days, respectively; p = 0.543).This study indicates that S-1 may be effective even in gastric scirrhous carcinoma with a high level of DPD activity.