naphthoquinones and Fever

YM155, a novel molecular targeted agent, suppresses survivin, a member of the inhibitor of apoptosis protein family that is overexpressed in many tumor types. The aim of this study was to determine the maximum tolerated dose (MTD) and to assess the safety, pharmacokinetics, and antitumor activity of YM155 in patients with advanced refractory solid tumors.. Patients with advanced refractory solid tumors were treated with escalating doses of YM155 administered by continuous i.v. infusion for 168 hours in 21-day cycles.. Of the 34 patients enrolled, 33 (median age, 59 years) received at least 1 dose of YM155 (range, 1-19 cycles). The dose levels studied were 1.8, 3.6, 4.8, 6.0, 8.0, and 10.6 mg/m(2)/d. The MTD was determined to be 8.0 mg/m(2)/d, based on a dose-limiting toxicity of increased blood creatinine observed in 2 patients receiving 10.6 mg/m(2)/d. The most common adverse reactions judged to be related to YM155 were urine microalbumin present; fever; injection-site phlebitis; fatigue; and decreased hemoglobin/anemia, blood albumin, and lymphocyte count. The pharmacokinetic profile was almost linear over the dosing range and was similar between cycles 1 and 2. Urinary excretion of YM155 showed no definite difference among doses. Stable disease was achieved in nine patients.. YM155 was safely administered to patients with advanced refractory solid tumors by 168-hour continuous i.v. infusion in 21-day cycles. The MTD was determined to be 8.0 mg/m(2)/d. The safety profile, plasma concentrations achieved, and antitumor activity observed merit further studies with this survivin suppressant, alone and in combination regimens.

Topics: Adult; Aged; Aged, 80 and over; Anemia; Dose-Response Relationship, Drug; Drug Administration Schedule; Fatigue; Female; Fever; Humans; Imidazoles; Infusions, Intravenous; Inhibitor of Apoptosis Proteins; Male; Metabolic Clearance Rate; Microtubule-Associated Proteins; Middle Aged; Naphthoquinones; Neoplasms; Patient Dropouts; Survivin; Treatment Outcome

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Antipyretics; Cytokines; Fever; Inflammation; Mice; Naphthoquinones; Plant Extracts; Prostaglandins

Two trials were conducted to compare the efficacy of parvaquone and buparvaquone for the treatment of naturally acquired East Coast fever (ECF, Theileria parva infection) which, if untreated, is almost invariably fatal in European breeds of cattle. In the first trial 28 naive cattle were exposed in a paddock infested with ticks carrying a virulent form of the disease. Twelve were treated with each drug when they developed clinical ECF. All 24 cattle were cured. In the second study, 100 cases of ECF occurring naturally on farms in Kenya were treated, 50 with each drug. Parvaquone cured 44 (88%) buparvaquone cured 45 (90%). Intercurrent infections, predominantly anaplasmosis and bacterial pneumonia or scour, were treated specifically. It is concluded that parvaquone and buparvaquone are similarly effective in curing ECF and cure rates are maximised by accurate diagnosis and prompt treatment of both ECF and intercurrent infections.

Topics: Administration, Topical; Animals; Antimalarials; Biopsy; Cattle; Female; Fever; Injections, Intramuscular; Insecticides; Kenya; Male; Naphthoquinones; Nitriles; Parasitemia; Pyrethrins; Random Allocation; Theileriasis; Tick Infestations

Topics: Adult; AIDS-Related Opportunistic Infections; Antifungal Agents; Atovaquone; Fever; HIV Infections; Humans; Male; Naphthoquinones