A total of 401 eligible patients with resected stages B and C colorectal carcinoma were randomly assigned to no-further therapy or to adjuvant treatment with either levamisole alone, 150 mg/d for 3 days every 2 weeks for 1 year, or levamisole plus fluorouracil (5-FU), 450 mg/m2/d intravenously (IV) for 5 days and beginning at 28 days, 450 mg/m2 weekly for 1 year. Levamisole plus 5-FU, and to a lesser extent levamisole alone, reduced cancer recurrence in comparison with no adjuvant therapy. These differences, after correction for imbalances in prognostic variables, were only suggestive for levamisole alone (P = .05) but quite significant for levamisole plus 5-FU (P = .003). Whereas both treatment regimens were associated with overall improvements in survival, these improvements reached borderline significance only for stage C patients treated with levamisole plus 5-FU (P = .03). Therapy was clinically tolerable with either regimen and severe toxicity was uncommon. These promising results have led to a large national intergroup confirmatory trial currently in progress.
Chemokines, together with key cytokines that promote their release are elevated in mucosal tissues from patients with IBD. It is likely that these chemokines play an important role in the perpetuation of tissue destructive inflammatory processes.
The clinical doubling times of human solid tumors are reviewed. Methods are also described for estimating subclinical tumor doubling times, and these methods are applied to Wilms' tumor, choriocarcinoma, Burkitt's tumor, and breast cancer. Rapidly growing tumors are often responsive to therapy, and such complete responses are often quite durable. Slowly growing tumors respond less favorably to therapy, and responses are generally not durable. Rapidly growing tumors in advanced stages are similar in their response behavior to the slowly growing tumors. A strategy based on cell kinetics principles and tumor doubling time data is proposed for improving therapeutic results in responsive tumors. Data on clinical and subclinical tumor doubling times are used to distinguish early recurrences from late recurrences in a given tumor type. Early recurrences call for intensification of induction therapy, whereas late recurrences call for prolongation of consolidative therapy. This strategy may also apply in adjuvant therapy of slowly growing tumors.
Anorexia, cachexia, and resultant weight loss are major clinical problems in a substantial proportion of patients with advanced cancer. Effective means of alleviating these problematic symptoms are lacking. Extensive clinical data demonstrate a weight enhancing effect for the serotonin antagonist, cyproheptadine, in several clinical situations. In addition, sound basic research suggests that cyproheptadine may be helpful in patients with cancer anorexia/cachexia. Because of this, the authors performed a randomized, placebo-controlled, double-blinded clinical trial using cyproheptadine, 8 mg orally three times a day in 295 patients with advanced malignant disease. Patients assigned to cyproheptadine had less nausea (P = 0.02), less emesis (P = 0.11), more sedation (P = 0.07), and more dizziness (P = 0.01) than placebo patients. Patients' appetites, measured by serial patient-completed questionnaires, appeared to be mildly enhanced by cyproheptadine. Unfortunately, cyproheptadine did not significantly abate progressive weight loss in these patients with advanced malignant disease; patients assigned to cyproheptadine lost an average of 4.5 pounds per month compared to 4.9 pounds per month for patients assigned to a placebo (P = 0.72).
SUMMARYBackground: Intravenous ciclosporin for acute, severe colitis is usually administered in a dose of 4 mg/kg/day, with concurrent intravenous steroids. This is associated with considerable morbidity. We have been using a lowdose regimen, most commonly without concurrent steroids, for seven years, and present the outcome. Methods: Records of all patients admitted for severe ulcerative colitis, treated by one physician over seven years, were reviewed. Results: Thirty-one patients received low-dose intravenous ciclosporin (2 mg/kg/day) for a median 8 days. Eleven early patients received concurrent intravenous corticosteroids. Three patients had hypertension
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