Irinotecan therapy in adults with recurrent or progressive malignant glioma.

PURPOSE: To determine the activity, toxicity, and pharmacokinetics of irinotecan (CPT-11, Camptosar; Pharmacia & Upjohn, Kalamazoo, MI) in the treatment of adults with progressive, persistent, or recurrent malignant glioma. PATIENTS AND METHODS: Patients with progressive or recurrent malignant gliomas were enrolled onto this study between October 1996 and August 1997. CPT-11 was given as a 90-minute intravenous (i.v.) infusion at a dose of 125 mg/m2 once weekly for 4 weeks followed by a 2-week rest, which comprised one course. Plasma concentrations of CPT-11 and its metabolites, SN-38 and SN-38 glucuronide (SN-38G), were determined in a subset of patients. RESULTS: All 60 patients who enrolled (36 males and 24 females) were treated with CPT-11 and all were assessable for toxicity, response, and survival. Pharmacokinetic data were available in 32 patients. Nine patients (15%; 95% confidence interval, 6% to 24%) had a confirmed partial response, and 33 patients (55%) achieved stable disease lasting more than two courses (12 weeks). Toxicity observed during the study was limited to infrequent neutropenia, nausea, vomiting, and diarrhea. CPT-11, SN-38, and SN-38G area under the plasma concentration-time curves through infinite time values in these patients were approximately 40%, 25%, and 25%, respectively, of those determined previously in patients with metastatic colorectal cancer not receiving antiepileptics or chronic dexamethasone treatment. CONCLUSION: Response results document that CPT-11, given with a standard starting dose and treatment schedule, has activity in patients with recurrent malignant glioma. However, the low incidence of severe toxicity and low plasma concentrations of CPT-11 and SN-38 achieved in this patient population suggest that concurrent treatment with anticonvulsants and dexamethasone enhances drug clearance.

Phase I trial of carmustine plus O6-benzylguanine for patients with recurrent or progressive malignant glioma.

PURPOSE: The major mechanism of resistance to alkylnitrosourea therapy involves the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase (AGT), which removes chloroethylation or methylation damage from the O(6) position of guanine. O(6)-benzylguanine (O(6)-BG) is an AGT substrate that inhibits AGT by suicide inactivation. We conducted a phase I trial of carmustine (BCNU) plus O(6)-BG to define the toxicity and maximum-tolerated dose (MTD) of BCNU in conjunction with the preadministration of O(6)-BG with recurrent or progressive malignant glioma. PATIENTS AND METHODS: Patients were treated with O(6)-BG at a dose of 100 mg/m(2) followed 1 hour later by BCNU. Cohorts of three to six patients were treated with escalating doses of BCNU, and patients were observed for at least 6 weeks before being considered assessable for toxicity. Plasma samples were collected and analyzed for O(6)-BG, 8-oxo-O(6)-BG, and 8-oxoguanine concentration. RESULTS: Twenty-three patients were treated (22 with glioblastoma multiforme and one with anaplastic astrocytoma). Four dose levels of BCNU (13.5, 27, 40, and 55 mg/m(2)) were evaluated, with the highest dose level being complicated by grade 3 or 4 thrombocytopenia and neutropenia. O(6)-BG rapidly disappeared from plasma (elimination half-life = 0. 54 +/- 0.14 hours) and was converted to a longer-lived metabolite, 8-oxo-O(6)-BG (elimination half-life = 5.6 +/- 2.7 hours) and further to 8-oxoguanine. There was no detectable O(6)-BG 5 hours after the start of the O(6)-BG infusion; however, 8-oxo-O(6)-BG and 8-oxoguanine concentrations were detected 25 hours after O(6)-BG infusion. The mean area under the concentration-time curve (AUC) of 8-oxo-O(6)-BG was 17.5 times greater than the mean AUC for O(6)-BG. CONCLUSION: These results indicate that the MTD of BCNU when given in combination with O(6)-BG at a dose of 100 mg/m(2) is 40 mg/m(2) administered at 6-week intervals. This study provides the foundation for a phase II trial of O(6)-BG plus BCNU in nitrosourea-resistant malignant glioma.

Central nervous system tumors in children.

OBJECTIVES: To examine how pediatric and adult central nervous system (CNS) tumors differ and to discuss the unique aspects of diagnosis, treatment, and long-term effects of brain tumors in children. DATA SOURCES: Research, review articles, book chapters, and abstracts. CONCLUSIONS: A child's growing and developing body and brain place him or her at great risk for permanent damage as a result of traditional treatment methods. A family-centered nursing approach assists the child and family in coping with the impact of a brain tumor. IMPLICATIONS FOR NURSING PRACTICE: Children have unique needs during and following treatment for CNS tumors. All oncology nurses need to be fully informed about and help monitor for intellectual, endocrinologic, and oncogenic late effects from the disease and treatment.

Parent consultants in the health-care system: a new approach in the care of children with special needs.

A unique and innovative role for parents has emerged from the recent emphasis on family-centered, community-based health care for children with special health-care needs. The role of parent consultant is described in the following article. Identified are the characteristics of the consultant role, benefits as well as challenges, how the role is enacted, and ways to finance the position. Nurses can serve to support and nurture the parent consultant role to ensure positive role development. Parent consultants have a unique and important perspective to offer in the delivery of a family-centered approach.

Pilot-scale studies on the effect of bromine addition on the emissions of chlorinated organic combustion by-products.

The addition of brominated organic compounds to the feed of a pilot-scale incinerator burning chlorinated waste has been found previously, under some circumstances, to enhance emissions of volatile and semivolatile organic chlorinated products of incomplete combustion (PICs) including polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCDDs/Fs). This phenomenon appears to be sensitive to temperature and combustion conditions. This paper reports on a study to evaluate the emissions of organic combustion by-products while varying amounts of bromine (Br) and chlorine (Cl) are being fed into a pilot-scale incinerator burning surrogate waste materials. The surrogate waste was fed at a constant molar halogen input rate, with varying Br/Cl molar ratios. In these tests, an approximately 30% decrease in the total PCDD/F concentrations due to the addition of Br was observed. This decrease appears to be a decrease only in the chlorinated dioxin and furan species; other halogenated dioxins and furans were formed instead. PCDD/F homologue distribution shifted towards the higher chlorinated species. Perhalogenated or nearly perhalogenated mixed bromo-chloro furans were also observed in quantities that could potentially account for the observed decrease in PCDDs/Fs. This research illustrates the need for careful trial burn planning if Br will be present in the facility's feed-stock during normal operation.

Family-centered care for the bereaved.

The death of a child is a severe and profound loss to all family members. The many tasks of the grieving process can be supported and facilitated by a bereavement program. The Whispers of Hope Bereavement Program at Duke University is a comprehensive, family-centered program providing periodic telephone contacts with a bereaved family, a series of letters containing grief education and support materials, and an annual Day of Remembrance for families and staff. A bereaved parent, clinical nurse specialist, and chaplain share program coordination at a cost per year of less than $20.00 per family. Program evaluation efforts to date suggest a high level of family satisfaction with the program.