[A phase I study of modified FOLFOX 6 therapy for advanced colorectal cancer].

Oxaliplatin (L-OHP) has been established as a key drug for advanced colorectal cancer, and combination therapy with 5-FU/Leucovorin (LV)(FOLFOX regimen) is commonly used in Europe and the US. A phase I study of modified (m) FOLFOX 6 therapy was conducted to determine the recommended dose (RD) of 5-FU infused for 46 hours. Inclusion criteria were unresectable advanced colorectal cancer,measurable lesions, performance status (PS; ECOG) 0-2, age 20-75 years, and adequate organ functions. L-OHP and l-LV was administered over 2 hours and followed by bolus injection and continuous infusion of 5-FU for 46 hours every 2 weeks. Two cycles of mFOLFOX 6 therapy were performed. Doses of L-OHP, l-LV, and bolus injection of 5-FU were fixed at 85 mg/m(2), 200 mg/m(2), and 400 mg/m(2), respectively. The dose of continuous infused 5-FU was escalated from 1,600 mg/m(2), (level 1), 2,000 mg/m(2), (level 2), 2,400 mg/m(2), (level 3), and 2,800 mg/m(2), (level 4). RD was determined in a dose escalation manner, and safety was evaluated according to NCI-CTC Ver 2.0. A total of 13 patients were enrolled. Male/female=7/6, PS 0/1/2=2/4/7, mean age 64 years (range 55-75). Thrombocytopenia was not observed, and grade 2 of neutropenia and peripheral neuropathy was observed in 4 and 6 out of 13 patients. No dose-limiting toxicity (DLT) was observed at level 1 (n=3), 2 (n=4), and 3 (n=4), but at level 4 (n=2), 2 patients experienced DLT; grade 3 easy fatigue and anorexia required treatment delay over 7 days. Level 3 was therefore determined as RD. A phase II study is ongoing to evaluate the efficacy of mFOLFOX 6 therapy.

[Bioprotection by local and whole-body preheating--bioprotection of damage to mice tongue from burning by local preheating of oral cavity and of radiation damage of small intestine from whole-body preheating].

We have reported the cytoprotective effects of HSP 70 on various stress damage induced by mild heating. In this study, we examined the cytoprotective effects of HSP 70 induced by the local preheating of the oral cavity of mice at 42 degrees C for 30 min, and the following results (1-4) were obtained. We also examined the cytoprotective effects against radiation injury by whole-body preheating at 41.3-41.6 degrees C for 30 min (5-6). 1) The concentration of HSP 70 in lymphocytes was increased 2 days after preheating, but not significantly. 2) The concentration of HSP 70 in masseter muscle was significantly increased 2 days after preheating. 3) Under non-heat stress (control), tongue muscle was strongly stained with immunoblotting of HSP 72 antibody, an antibody of induced-type HSP 70. 4) Tongue damage and weight loss of the mice in the preheating group, whose tongues were burned, were less than in the control group. These results showed that HSP 70 induced by local preheating of the oral cavity protected against tongue damage from burning. 5) Radiation injury of the small intestine on HE stain of whole-body radiated mice was obviously reduced by whole-body preheating. 6) Decrease of the ratio of the villus length to the crypt of whole body-irradiated mice was significantly improved by whole-body preheating. From these results, it was concluded that local and whole-body preheating were useful for cytoprotection from stressful damage.