A Preliminary Report of Phase I and II Study of N4-Behenoyl-1-{beta}-D-arabinofuranosylcytosine (BH-AC) in Patients with Acute Leukemia and Other Malignancies

N⁴-Behenoy1-1-ß-D-arabinofuranosy1cytosine (BH-AC)was administered to 11 patients with acute leukemia and fivepatients with other malignancies in a Phase I and TI clinicaltrial. Among 16 patients, 14 received BH-AC after being refractoryto prior therapies, and two with acute leukemia received BH-ACfor their first remission induction therapy. The starting dose was 1.5mg/kg administered as a single i.v.infusion of three hours. The doses were then escalated up to5.0 mg/kg. No side effects were noted with single i.v. infusions.Daily consecutive infusions of 2.0 mg to 6.0 mg/kg for fourto 21 days resulted in two patients experiencing nausea, twoanorexia and one developing skin eruptions. Significant hematologicaleffects were noted by the daily infusions. One patient withacute myeloblastic leukemia achieved complete remission with5.0 mg/kg BH-AC administered daily for 21 days. BH-AC is active in acute leukemia and may play a role in thecombination regimens for this disease.     

A prospective randomized study of amoxycillin and omeprazole with and without metronidazole in the eradication treatment of Helicobacter pylori

A combination of amoxycillin and omeprazole is often used to treat Helicobacter pylori infection. A three-drug regimen comprising metronidazole, amoxycillin and omeprazole has been proposed as an alternative therapy. In a prospective, randomized, comparative study, we evaluated these two regimens with respect to safety and ef?cacy in patients with H. pylori infection. Sixty patients with peptic ulcer (gastric, 32 patients; duodenal, 28 patients) who had a history of ulcer recurrence were randomly assigned to dual therapy with amoxycillin (500 mg three times daily for 2 weeks) and omeprazole (20 mg once daily for 8 weeks) or to triple therapy with metronidazole (500 mg twice daily for 2 weeks) plus amoxycillin and omeprazole, given in the same dosages as dual therapy. Forty-eight patients completed the protocol; treatment was discontinued because of side effects in nine patients, and three patients dropped out of the study. On the basis of all patients treated, the rate of H. pylori eradication was signi?cantly higher for triple therapy 20/23 cases, 87.0%; 95% con?dence interval (CI), 0.664–0.972) than for dual therapy 13/25, 52.0%; 0.313–0.722; P < 0.05). On an intention-to-treat basis, the difference between the groups in the rate of H. pylori eradication was marginally signi?cant (P= 0.06 [0.028–0.512]). Side effects were reported by ?ve patients receiving triple therapy (skin rash, one; nausea, two; headache, one; abdominal pain, one), and four patients receiving dual therapy (skin rash, two; abdominal pain, one; diarrhoea, one). All side effects resolved spontaneously after termination of treatment. There was no signi?cant difference in safety between the two regimens. Triple therapy with metronidazole, amoxycillin, and omeprazole was signi?cantly more effective for the eradication of H. pylori than dual therapy with amoxycillin and omeprazole alone. The safety of these regimens was similar, and triple therapy was found to be clinically acceptable.