Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diaziquone (AZQ), a synthetic quinone with demonstrated activity against acute nonlymphocytic leukemia (ANLL), primary CNS tumors, and non-Hodgkin's lymphoma (NHL), is virtually devoid of nonhematopoietic toxicity at conventional doses. As a prelude to its inclusion into bone marrow transplant (BMT) preparative regimens, a phase I study of high-dose AZQ with autologous BMT (ABMT) was performed. Patients with refractory solid tumors and lymphomas were treated with a single 24-hour infusion of AZQ at 50 to 355 mg/m2 in dose escalations of 20%. Fifty-six patients received 69 courses. Those receiving greater than 60 mg/m2 had nadir granulocyte and platelet counts less than 500/microL and 20,000/microL, respectively. Nausea, vomiting, stomatitis, and diarrhea were mild, transient, and not dose-related. Transient minimal elevations of liver function tests were seen in five patients and were also not dose-related. The maximally tolerated dose (MTD) of high-dose AZQ was found to be 245 mg/m2, with nephrotoxicity being dose-limiting. Significant azotemia was seen in four of 12 patients treated at 295 and 355 mg/m2, including fatal anuric renal failure in three of these patients. Reversible proteinuria also occurred in 24 of 26 courses above 150 mg/m2, including nephrotic range proteinuria in eight courses, all at doses of 205 to 355 mg/m2. The proteinuria was also associated with multiple proximal tubular defects including generalized aminoaciduria and proximal renal tubular acidosis. There were six early deaths including two of early renal failure (295 and 355 mg/m2), two of sepsis (205 and 245 mg/m2), one of a pulmonary embolus (85 mg/m2), and one of progressive disease (60 mg/m2). Of 50 patients who were assessable for response, there were seven responses including two of 10 with primary CNS tumors, one of 12 with malignant melanoma, one of five with non-small-cell lung carcinoma, two of two with breast carcinoma, and one of one with ovarian carcinoma. Because of its activity in ANLL and NHL and its unique toxicity spectrum, high-dose AZQ may improve the efficacy of current BMT preparative regimens without significantly increasing their nonhematopoietic toxicity.
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PMID:A phase I trial of high-dose diaziquone and autologous bone marrow transplantation: an Illinois Cancer Council study. 207 48

Bevacizumab is increasingly being used in adult patients with cancer and children with central nervous system (CNS) tumors. Little, however, is known about the efficacy, risks, and benefits of bevacizumab administration in non-CNS tumors of childhood. The aim of the present study was to report on bevacizumab administered as add-on-therapy for poor prognosis non-CNS solid tumors of childhood and adolescence, including a prospective evaluation of side effects of bevacizumab. Seven patients (female: n = 5; median age, 14.5 years) with relapsed (n = 4) or primary metastatic (n = 3) solid non-CNS tumors received bevacizumab at 5-10 mg/kg body weight intravenously every 2-3 weeks. Assessment of cardiac function, thyroid hormone levels, urine analysis, and radiographic responses were carried out every 3 months. The median time of bevacizumab treatment was 10 (range, 5-17) months. Patients received a median of 16 (range, 10-38) bevacizumab infusions. With a median follow-up of 25 (range, 13-38) months, five patients relapsed after 7-25 months and three of them died. Two patients are still in complete remission for 31 and 32 months, respectively. Fraction shortening decreased in two patients. Bevacizumab was associated with new-onset increase in basal thyroid-stimulating hormone (n = 3), mild proteinuria/hematuria (n = 5), intermittent hypertension (n = 2), hypertension requiring antihypertensive medication (n = 3), and epistaxis (n = 2). In two patients, therapy with bevacizumab was terminated because of side effects. Selected patients with relapsed or primary metastatic solid non-CNS tumors of childhood and adolescence might benefit from add-on-therapy with bevacizumab. Although the side effects were usually mild, cardiac monitoring seems to be essential during and after the administration of bevacizumab.
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PMID:Add-on-therapy with bevacizumab in children and adolescents with poor prognosis non-CNS solid tumors. 2315 63