Survival following intensive preoperative combined modality therapy with paclitaxel, cisplatin, 5-fluorouracil, and radiation in resectable esophageal carcinoma: a phase I report.

Purpose: To assess the benefits of aggressive chemoradiation therapy followed by surgery in resectable esophageal carcinoma.

Method: Twenty-nine patients with resectable carcinoma were treated with 60 Gy of radiation (2 Gy daily for 6 weeks) and concurrent chemotherapy consisting of continuous infusion of 5-fluorouracil (200-225 mg/m(2)/d), paclitaxel (25, 40, 50, or 60 mg/m(2)) weekly over 1 hour, and cisplatin (25 mg/m(2)) weekly immediately following paclitaxel throughout radiation. Patients received either 4 cycles of postoperative paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks or paclitaxel 175 mg/m(2) over 3 hours and cisplatin 75 mg/m(2) every 3 weeks prior to the initiation of chemoradiation.

Chronic dosing of oltipraz in people at increased risk for colorectal cancer.

The dithiolethione oltipraz is being developed as a chemopreventive agent for many malignancies, including colorectal cancer, on the basis of its in vivo protective activity against chemically induced tumors in a variety of animal models. This protection has been associated with an enhanced capacity to detoxify reactive carcinogens and, more recently, with increased DNA repair. In a previous single-dose study, elevated detoxification gene expression was observed in the days after oltipraz dosing.

Preclinical and clinical evaluation of broccoli supplements as inducers of glutathione S-transferase activity.

Previous studies suggest that cruciferous vegetables may provide protection against carcinogen exposure by inducing detoxification enzymes. ICR(Ha) mice were gavaged with broccoli tablets (1 g/kg), and colon tissues were collected after treatment. Glutathione S-transferase (GST) activity was assayed and peaked on days 1 and 2 after treatment, respectively (P = 0.

Modulation of gene expression in subjects at risk for colorectal cancer by the chemopreventive dithiolethione oltipraz.

Prolonged exposure to mutagenic substances is strongly associated with an individual's risk of developing colorectal cancer. Clinical investigation of oltipraz as a chemopreventive agent is supported by its induction of the expression of detoxication enzymes in various tissues, and its protective activity against the formation of chemically induced colorectal tumors in animals. The goals of the present study were: to determine if oltipraz could induce detoxicating gene expression in human tissues; to identify effective non-toxic doses for more extensive clinical testing; and to establish a relationship between effects in the colon mucosa and those in a more readily available tissue, the peripheral mononuclear cell.

Glutathione S-transferase activity and glutathione S-transferase mu expression in subjects with risk for colorectal cancer.

The glutathione S-transferases (alpha, mu, and pi), a family of Phase II detoxication enzymes, play a critical role in protecting the colon mucosa by catalyzing the conjugation of dietary carcinogens with glutathione. We investigated the efficacy of using the glutathione S-transferase (GST) activity of blood lymphocytes and GST-mu expression as biomarkers of risk for colorectal cancer. GST activity was measured in the blood lymphocytes of control individuals (n = 67) and in the blood lymphocytes (n = 60) and colon tissue (n = 34) of individuals at increased risk for colon cancer.