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Background: Colorectal cancer (CRC) is one of the most commonly occurring neoplasms and a leading cause of cancer death worldwide, and new preventive strategies are needed to lower the burden of this disease. Eicosapentaenoic acid (EPA), the omega-3 polyunsaturated fatty acid that is widely used in the treatment of hyperlipidemia and prevention of cardiovascular disease, has recently been suggested to have a suppressive effect on tumorigenesis and cancer cell growth. In CRC chemoprevention trials, in general, the incidence of polyps or of the cancer itself is set as the study endpoint. Although the incidence rate of CRC would be the most reliable endpoint, use of this endpoint would be unsuitable for chemoprevention trials, because of the relatively low occurrence rate of CRC in the general population and the long-term observation period that it would necessitate. Moreover, there is an ethical problem in conducting long-term trials to determine whether a test drug might be effective or harmful. Aberrant crypt foci (ACF), defined as lesions containing crypts that are larger in diameter and stain more darkly with methylene blue than normal crypts, are considered as a reliable surrogate biomarker of CRC. Thus, we devised a prospective randomized controlled trial as a preliminary study prior to a CRC chemoprevention trial to evaluate the chemopreventive effect of EPA against colorectal ACF formation and the safety of this drug, in patients scheduled for polypectomy. Methods: This study is a multicenter, double-blind, placebo-controlled, randomized controlled trial to be conducted in patients with both colorectal ACF and colorectal polyps scheduled for polypectomy. Eligible patientsshall be recruited for the study and the number of ACF in the rectum counted at the baseline colonoscopy. Then, the participants shall be allocated randomly to either one of two groups, the EPA group and the placebo group. Patients in the EPA group shall receive oral 900-mg EPA capsules thrice daily (total daily dose, 2.7 g per day), and those in the placebo group shall receive oral placebo capsules thrice daily. After one month’s treatment with EPA/placebo, colonoscopic examination and polypectomy will be performed to evaluate the formation of ACF, and the cell-proliferative activity and cell-apoptotic activity in normal colorectal mucosa and colorectal polyps.Discussion: This is the first study proposed to explore the effect of EPA against colorectal ACF formation in humans. This trial has been registered in the University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000008172. [ABSTRACT FROM AUTHOR]

To assess the maximum tolerated dose, safety, and pharmacokinetic (PK) profile of escalating doses of the novel topoisomerase I (topo I) inhibitor edotecarin (J-107088) given as a 2-h intravenous (IV) infusion once every 21 days in patients with advanced solid tumors who had not responded to standard therapy. Twenty-nine patients (18M:11F) received a 2-h IV infusion of edotecarin in doses of 6, 8, 11, 13, or 15 mg/m2 every 21 days (with an additional 1–2 weeks permitted for recovery) and were evaluated for safety, PK, and tumor response. The most common non-hematologic toxicities were grade 1–2 nausea, fatigue, anorexia, vomiting, and fever. The most common hematologic toxicities were grade 1–2 thrombocytopenia and grade 3–4 neutropenia, leukopenia, and anemia. No grade 3–4 diarrhea was reported. Dose-limiting toxicities were observed in four patients at the 15 mg/m2 dose and one patient at the 13 mg/m2 dose. These toxicities included grade 3 nausea, vomiting, headache, and fatigue, as well as grade 4 neutropenia and febrile neutropenia. The maximum tolerated dose was declared at 15 mg/m2. One patient with bladder cancer had a confirmed partial response at a dose of 13 mg/m2. There was a trend to dose-proportional increases in edotecarin peak plasma concentrations and area under the curve values. Renal excretion of edotecarin was minimal (3–8% of the dose). The recommended Phase II dose of edotecarin is 13 mg/m2 once every 21 days. The toxicities in this study were those typical of cytotoxic chemotherapy and less severe than those associated with other topo I inhibitors. The observed safety profile and preliminary evidence of clinical benefit warrant further investigation of this drug as monotherapy or part of combination therapy in patients with solid tumors. [ABSTRACT FROM AUTHOR]