A randomized phase II study comparing preoperative mFOLFOX6 versus FOLFOXIRI for locally advanced colon cancer: JCOG2006.

The prognosis of locally advanced colon cancer (LACC) with surgical resection followed only by adjuvant chemotherapy is poor. Preoperative chemotherapy for LACC patients with risk factors such as cT4bN+ or cT3-4aN2-3 has attracted attention. Here, the authors describe the rationale and design of JCOG2006, a randomized phase II study comparing preoperative chemotherapy with mFOLFOX6 versus FOLFOXIRI for LACC. Their efficacy and safety are evaluated and a determination of which is the more promising treatment will be conducted in a subsequent phase III trial. A total of 86 patients will be accrued from 44 institutions over 2 years. The primary end point is the proportion of patients with a Tumor Regression Score of 0-2, and secondary end points include overall survival, response rate and adverse events. Clinical Trial Registration: jRCTs031210365 (https://jrct.niph.go.jp/).

Effects of change in the formulation of lanthanum carbonate on laboratory parameters.

Lanthanum carbonate (LC) is available in the two formulations of chewable tablets and granules. In this study, we changed the formulation of LC from chewable tablet to granules, and compared the laboratory parameters for 3 months before and after changing formulation in 58 hemodialysis (HD) patients. We also surveyed patients about their preferences for the two formulations. The mean serum phosphorus (P) levels decreased significantly (P < 0.01) from 6.7 mg/dL to 6.4 mg/dL after the change. The levels for serum albumin and geriatric nutritional risk index increased significantly (P < 0.01). Serum calcium levels also increased significantly (P < 0.01), while serum intact parathyroid hormone levels decreased significantly (P < 0.01). In the survey, approximately half of the patients responded that the granules were easier to take than the chewable tablets. These findings suggest that changing the formulation of LC to granules may reduce serum P levels of the HD patients in clinical practices.

Safety and efficacy of modified FOLFOX6 plus high-dose bevacizumab in second-line or later treatment of patients with metastatic colorectal cancer.

AIM: The aim of this retrospective study was to show the efficacy and safety of modified FOLFOX6 plus high-dose bevacizumab (10 mg/kg/2 weeks) in the second-line or later treatment of metastatic colorectal cancer. METHODS: A total of 24 consecutive patients treated between August 2007 and August 2009 were included in this retrospective study. None of the patients had received bevacizumab as part of prior treatment. RESULTS: All 24 patients received modified FOLFOX6 plus high-dose bevacizumab and were followed for a median of 36.9 months. Overall response rate was 29%. Median progression-free survival was 7.5 months, and median overall survival was 17.3 months. Grade 3/4 adverse events were: neutropenia (54.2%), leukopenia (25.0%), neuropathy (12.5%), hypertension (12.5%), thrombocytopenia (8.3%), and decreased haemoglobin, gastrointestinal haemorrhage, wound complications, nausea, diarrhoea, mucositis and fatigue (each 4.2%). CONCLUSION: Modified FOLFOX6 plus high-dose bevacizumab may be useful in the second-line treatment of patients with metastatic colorectal cancer who have not received bevacizumab.

Dose-dependent promotion of rat forestomach carcinogenesis by combined treatment with sodium nitrite and ascorbic acid after initiation with N-methyl-N'-nitro-N-nitrosoguanidine: possible contribution of nitric oxide-associated oxidative DNA damage.

Dose-dependent promotion effects of combined treatment with sodium nitrite (NaNO2) and ascorbic acid (AsA) on gastric carcinogenesis were examined in rats pretreated with N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Groups of 15 6-week-old F344 male rats were given 0.01% MNNG in their drinking water for 10 weeks to initiate carcinogenesis in the glandular stomach and a single intragastric administration of 100 mg/kg/bodyweight of MNNG by stomach tube at week 9 to initiate carcinogenesis in the forestomach. From week 11, they received either drinking water containing 0.05, 0.1 or 0.2% NaNO2 and a diet supplemented with 0.1 or 0.2% AsA in combination, each individual chemical alone or a basal diet until the end of week 42. In the forestomach, the incidence of hyperplasia was increased dose dependently by the treatment with NaNO2 alone. Incidences of neoplastic lesions were dramatically increased by the combined treatment with NaNO2 and AsA in a dose-dependent manner, but AsA itself had no effect. In the glandular stomach, only toxicity and regenerative changes were increased by the high-dose combination. In a second short-term experiment conducted for sequential observation, necrosis and strong inflammation were found in the forestomach epithelium shortly after commencing combined treatment with 1.0% AsA and 0.2% NaNO2, followed by hyperplasia, whereas there were no obvious effects in the glandular stomach. In addition, after a 4 h treatment with 1.0% AsA and 0.2% NaNO2, a slight increase in the 8-hydroxy-deoxyguanosine levels in the forestomach epithelium was observed by high-performance liquid chromatography and an electrochemical detection system, albeit without statistical significance. In vitro, electron spin resonance demonstrated nitric oxide formation during incubation with NaNO2 and AsA under acidic conditions. Thus, NaNO2 was demonstrated to exert promoter action in the forestomach, with AsA acting as a strong copromoter through cytotoxicity and regenerative cell proliferation, possibly mediated by oxidative DNA damage, but the combined treatment with NaNO2 and AsA had little influence on glandular stomach carcinogenesis.