Sorafenib in patients with metastatic gastrointestinal stromal tumors who failed two or more prior tyrosine kinase inhibitors: a phase II study of Korean gastrointestinal stromal tumors study group.

PURPOSE: To evaluated the efficacy and safety of sorafenib in patients with advanced gastrointestinal stromal tumors (GIST) who failed to previous standard treatments. EXPERIMENTAL DESIGN: Thirty-one patients with measurable metastatic GIST who failed both imatinib and sunitinib were accrued. Sorafenib was administered orally at 400 mg twice daily until disease progression or development of intolerance. The primary endpoint was disease control rate (response + stable disease, DCR) at 24 weeks. RESULTS: Sorafenib was well tolerated, with hand-foot skin reaction, fatigue, hypertension, and abdominal pain being the most frequent adverse events. The relative dose intensity of sorafenib during the first 6 months was >80%. Four patients achieved partial response (response rate 13%, 95% CI 1-25%), and 16 (52%) had stable disease. DCR at 24 weeks was measured as 36% (95% CI 19-52%). Median progression-free and overall survivals were 4.9 and 9.7 months, respectively. Progression-free survival of patients with prior use of nilotinib (P = .0085) and with primary genotypes other than KIT exon 11 mutation (P = .0341) was significantly shorter than that of patients without. CONCLUSIONS: Sorafenib showed antitumor activity in this population of imatinib and sunitinib pretreated GIST. With sorafenib, about one third of patients can maintain disease control for more than 24 weeks.

Effect of supplementation of Bacillus subtilis LS 1-2 to broiler diets on growth performance, nutrient retention, caecal microbiology and small intestinal morphology.

Present study investigated the effect of dietary supplementation of Bacillus subtilis LS 1-2 on growth performance, apparent nutrient retention, caecal microbial population and intestinal morphology in broilers. Three hundred and twenty day-old Ross broiler chicks were randomly allotted to four treatments on the basis of BW in a randomized complete block design. Experimental diets were fed in two phases: starter (d 0-21) and finisher (d 22-35). Dietary treatments were basal diet supplemented with 0% (control), 0.15%, 0.30% and 0.45% B. subtilis LS 1-2. Supplementation of increasing levels of B. subtilis LS 1-2 showed linear improvement (P<0.05) in growth performance and apparent nutrient retention. At d 35, birds supplemented with increasing levels of B. subtilis LS 1-2 showed decrease in caecal Clostridium and Coliform count (linear, P<0.05). Moreover, supplementation of B. subtilis LS 1-2 increased (linear, P<0.05) villus height and villus height to crypt depth ratio in both duodenum and ileum. Results obtained in the present study indicate that B. subtilis LS 1-2 can be used as a growth promoter in broiler diets and can improve intestinal microbial balance and gut health of broilers.

Effect of supplementation of multi-microbe probiotic product on growth performance, apparent digestibility, cecal microbiota and small intestinal morphology of broilers.

The present study investigated the effect of inclusion of multi-microbe probiotic product on growth performance, apparent digestibility of nutrients, cecal microbiota and small intestinal morphology in broilers. Four hundred days-old Ross chicks were randomly allotted to five treatments on the basis of body weight (BW). Each treatment had four replicates of 20 chicks in each. Experimental diets were fed in two phases, starter (day 0-21) and finisher (day 22-35). Dietary treatments were; basal diet without any antimicrobial (NC), basal diet added with 20 mg Avilamycin/kg of diet (PC), 10(7) cfu multi-microbe probiotic/kg of diet (P1), 10(8) cfu multi-microbe probiotic/kg of diet (P2), and 10(9) cfu multi-microbe probiotic/kg of diet (P3). Overall BW gain and feed conversion ratio were better (p < 0.05) for treatments PC, P2 and P3 compared with NC and P1, with P1 being better (p < 0.05) than NC. Overall feed intake in treatments PC, P1, P2 and P3 were greater (p < 0.05) than NC. Apparent digestibility of dry matter and crude protein were greater (p < 0.05) in treatments PC, P2 and P3 compared with NC, with P1 being intermediate and not different form NC, PC, P2 and P3. At d 21 and 35, treatments PC, P1, P2 and P3 showed lower (p < 0.05) cecal Clostridium and Coliforms count in relation to NC. Moreover, cecal Clostridium (d 21) and Coliforms (d 21 and 35) count were lower (p < 0.05) in treatment PC in relation to P1; with P2 and P3 being intermediate and not different from PC. However, there was no effect of dietary treatments on cecal total anaerobic bacteria and Bifidobacterium spp. count. The villus height of duodenum in treatment PC was greater (p < 0.05) than NC, with P1, P2 and P3 being intermediate. Villus height of ileum in treatment PC was greater (p < 0.05) than in treatments P1 and NC, whereas it remained comparable among treatments PC, P2 and P3. Villus height to crypt depth ratio of ileum was greater (p < 0.05) for treatment PC, P2 and P3 compared with that in P1 and NC. It is concluded that multi-microbe probiotic inclusion at 10(8) and 10(9) cfu/kg diet had beneficial effects on broilers growth performance, apparent digestibility of nutrients and intestinal morphology and can be used as replacement to antibiotics growth promoter in broiler nutrition.

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma.

AIM: This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. METHODS: From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB-IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m(2) (days 1, 8, 29 and 36), doxorubicin 30 mg/m(2) (days 1 and 29) and mitomycin-C 10 mg/m(2) (day 1), every 8 weeks for 6 months. RESULTS: The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB (p=0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB (p<0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). CONCLUSIONS: Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.

Phase II study of capecitabine and cisplatin as first-line combination therapy in patients with gastric cancer recurrent after fluoropyrimidine-based adjuvant chemotherapy.

To evaluate the efficacy and safety of capecitabine and cisplatin in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant therapy. Patients with histologically confirmed and measurable advanced gastric cancer that had relapsed after fluoropyrimidine-based adjuvant chemotherapy received oral capecitabine (1250 mg m(-2) twice daily, days 1-14) and intravenous cisplatin (60 mg m(-2) over 1 h, day 1) every 3 weeks. In total, 32 patients were enrolled, of whom 30 were evaluable for efficacy and 32 for safety. A median of 5 cycles (range 1-10) was administered. One patient achieved a complete response and eight had partial responses, giving an overall response rate of 28% (95% CI, 13-44%). The median time to progression and median overall survival were 5.8 months (95% CI, 4.1-7.5 months) and 11.2 months (95% CI, 5.5-16.9 months), respectively. Grade 3 neutropenia and thrombocytopenia were observed in 38 and 6% of patients, respectively. Grade 2/3 nonhaematological toxicities included diarrhoea (19%), stomatitis (19%) and hand-foot syndrome (31%). No grade 4 toxicity, neutropenic fever or treatment-related deaths occurred. Capecitabine in combination with cisplatin was effective and well tolerated as first-line treatment in patients with recurrent gastric cancer after fluoropyrimidine-based adjuvant chemotherapy.