S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial).

BACKGROUND: S-1 is an oral fluoropyrimidine whose antitumor effects have been demonstrated in treating various gastrointestinal cancers, including metastatic colon cancer, when administered as monotherapy or in combination chemotherapy. We conducted a randomized phase III study investigating the efficacy of S-1 as adjuvant chemotherapy for colon cancer by evaluating its noninferiority to tegafur-uracil plus leucovorin (UFT/LV). PATIENTS AND METHODS: Patients aged 20-80 years with curatively resected stage III colon cancer were randomly assigned to receive S-1 (80-120 mg/day on days 1-28 every 42 days; four courses) or UFT/LV (UFT: 300-600 mg/day and LV: 75 mg/day on days 1-28 every 35 days; five courses). The primary end point was disease-free survival (DFS) at 3 years. RESULTS: A total of 1518 patients (758 and 760 in the S-1 and UFT/LV group, respectively) were included in the full analysis set. The 3-year DFS rate was 75.5% and 72.5% in the S-1 and UFT/LV group, respectively. The stratified hazard ratio for DFS in the S-1 group compared with the UFT/LV group was 0.85 (95% confidence interval: 0.70-1.03), demonstrating the noninferiority of S-1 (noninferiority stratified log-rank test, P < 0.001). In the subgroup analysis, no significant interactions were identified between the major baseline characteristics and the treatment groups. CONCLUSION: Adjuvant chemotherapy using S-1 for stage III colon cancer was confirmed to be noninferior in DFS compared with UFT/LV. S-1 could be a new treatment option as adjuvant chemotherapy for colon cancer. CLINICALTRIALSGOV: NCT00660894.

Evaluation of calcium hydroxide-containing root canal sealers with an improved rabbit ear chamber.

An improved rabbit ear chamber was used to evaluate calcium hydroxide-containing root canal sealers on their potential to induce dystrophic calcification in connective tissue. Four sealers and two control materials were introduced into the chambers and the effects of these materials on the living vascular tissue were observed continuously under a biomicroscope up to 9 weeks. Conventional histopathological investigation and examinations with a scanning electron microscope and an X-ray microanalyzer were done to supplement the results. Sealapex and Calvital (Ca(OH)2 + iodoform) revealed almost the same tissue reaction as calcium hydroxide-saline paste; they rapidly made a precipitate-barrier of calcium phosphate in the connective tissue, inducing calcification. However, Dentalis KEZ (ZnO-Ca(OH)2 + eugenol) caused mild disorders of microcirculation without calcification, as well as Canals (ZnO + eugenol). New A (Ca(OH)2 + fatty acid) had good compatibility with microvessels as well as New B (ZnO + fatty acid), however they induced no calcification and disintegrated rapidly in the tissue. These sealers were reclassified according to what they actually bring about in the tissue, not according to what they include.

Synthesis of a glycopeptide with phytoalexin elicitor activity. I. Synthesis of a triglycosyl L-serine and a triglycosyl L-seryl-L-proline dipeptide.

A stereocontrolled synthesis of the model compound for the phytoalexin elicitor-active glycoprotein is described. Glycosylation of the disaccharide, 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosyl-(1-->6)-2,3,4-tri-O-acetyl- alpha- D-mannopyranosyl trichloroacetimidate, with N-(carbobenzoxy)-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->3)-L- serine methyl ester or N-(carbobenzoxy)-(2,3,4-tri-O-acetyl-alpha-D-mannopyranosyl)-(1-->3)-L- seryl-L- proline methyl ester by use of AgOTf gave the desired trisaccharide-serine or trisaccharide-seryl-proline derivatives, which were transformed into beta-D-glucopyranosyl-(1-->6)-alpha-D-mannopyranosyl-(1-->6)-alpha-D- mannopyranosyl-(1-->3)-L-serine and triglycosyl-(1-->3)-L-seryl-L-proline via removal of the N-carbobenzoxy group, followed by deacylation.

[Hepatic arterial chemotherapy combined with hyperthermia or arterial embolization in unresectable liver tumor].

Fifty-four patients with unresectable malignant liver tumors (14 of hepatocellular carcinoma, 40 of metastasis to the liver from gastric or colo-rectal cancer) were treated with intra-hepato-arterial (IHA) injections of cis-diamminedichloroplatinum (II) (CDDP) plus 5-fluorouracil (5-FU). In 32 of the patients, the liver tumors were detected synchronously with the diagnosis of the primary cancers, which were resected palliatively. Therapeutic schedules consisted of bolus injections of CDDP (50 mg/body/week) and 5-FU (250 mg/body/day) [Regimen I], and CDDP (50 mg/body/10-14 days) and 5-FU (100 mg/body/day) [Regimen II]. In 48 patients treated with IHA chemotherapy only, a partial response (PR) was obtained in 6 of 14 (43%) evaluable patients for Regimen I and in 11 of 30 (37%) patients for Regimen II. The dose-limiting factor for treatment with CDDP was bone marrow toxicity, but this toxicity was remarkably alleviated in Regimen II without any decrease in antitumor effectiveness. In 13 patients, other modalities, such as total-body hyperthermia (4 patients), radiofrequency capacitive local hyperthermia (5), and temporary arterial embolization (4), were combined with IHA chemotherapy. PR was obtained in 7 of 13 (54%) patients with the combined therapy. This combined therapy was efficacious in 7 patients in whom no desired results were obtained by IHA chemotherapy only. The survival rate was 50% at 12 months. IHA chemotherapy with CDDP plus 5-FU, especially when according to Regimen II, appears to be a strongly recommended strategy for treatment of unresected primary or metastatic liver tumor. Further, addition of the hyperthermia or the arterial embolization might enhance the antitumor effect of IHA chemotherapy.

[Clinical results and problems of total-body thermochemotherapy].

The clinical results and problems of extracorporeally-induced total-body thermochemotherapy (TBHT) for recurrent cancer are presented. A total of 127 hyperthermic treatments were performed in 45 patients who had undergone unsuccessful conventional systemic anticancer chemotherapy. Partial response was observed in 11 of 34 evaluable patients (32%). In analysing the anticancer effects of TBHT according to cancer site, a high efficacy was observed in patients with their main tumor in the lung, liver and lymph nodes. The anticancer effects were most enhanced when TBHT was performed in combination with cisplatin and 5-fluorouracil. In order to augment the anticancer effects of TBHT, the choice of combined agents and administration timing are important. A useful method for determining the thermochemosensitivity of individual cancer cells to agents selected for drug treatment is the human tumor clonogenic assay. Furthermore, the usefulness of angiotensin II-induced hypertensive chemotherapy during TBHT for augmenting selective drug delivery to cancer tissue is stressed.

Synthesis and determination of configuration of natural 25-hydroxyvitamin D(3) 26,23-lactone.

The four stereoisomers of 25-hydroxyvitamin D(3) 26,23-lactone were synthesized by a stereoselective lactonization method. Natural 25-hydroxyvitamin D(3) 26,23-lactone was produced from 25-hydroxy-[3alpha-(3)H]vitamin D(3) by in vitro incubation of kidney homogenate prepared from vitamin D-supplemented chickens or was isolated from the serum of rats given 1,25-dihydroxyvitamin D(3) and 25-hydroxy-[3alpha-(3)H]vitamin D(3). The four synthetic isomers and the naturally produced 25-hydroxyvitamin D(3) 26,23-lactone were subjected to high-performance liquid chromatography in a system capable of separating the four isomers. The natural lactone comigrated with synthetic (23S,25R)-25-hydroxyvitamin D(3) 26,23-lactone, establishing it as the natural vitamin D(3) metabolite.