Granisetron vs ondansetron for prevention of nausea and vomiting in hematopoietic stem cell transplant patients: results of a prospective, double-blind, randomized trial.

The serotonin type-3 (5-HT3) antagonists represent a significant advance in the prevention of acute nausea and vomiting (N/V) from highly emetogenic chemotherapy. We sought to determine if any differences in efficacy or adverse effects exist between two such agents, ondansetron and granisetron, during conditioning therapy for hematopoietic stem cell transplantation (HSCT). Patients were randomized to receive either ondansetron 0.15 mg/kg intravenously every 8 h or granisetron 10 microg/kg intravenously daily. Additionally, all patients received scheduled dexamethasone and lorazepam. Prophylaxis was continued until 24 h after completion of chemotherapy. Nausea and distress were measured subjectively with visual analog scales and emetic episodes were quantified. Of the 110 randomized patients, 96 were evaluable for efficacy and safety. No significant differences in efficacy were observed between the ondansetron- and granisetron-treated patients, evaluated by comparing the degree of nausea and distress, number of emetic episodes and overall control of emesis. The adverse effects were also comparable and no patients were removed from study because of severe toxicities. This trial demonstrates that ondansetron and granisetron are equally effective at preventing acute N/V associated with conditioning therapy frequently used for HSCT. The agent of choice should be based on drug acquisition cost or preference.

Pegaspargase: an alternative?

OBJECTIVE: To review the chemistry, pharmacology, pharmacokinetics, clinical activity, adverse effects, dosage, and administration guidelines for pegaspargase. DATA SOURCES: A MEDLINE search (1980-1996), a CANCERLIT search (1983-1996), and a CURRENT CONTENTS search (1980-1996) using the terms pegaspargase, PEG-asparaginase, PEG-L-asparaginase, polyethylene glycol L-asparaginase, polyethylene glycol conjugated L-asparaginase, and Oncaspar were conducted. STUDY SELECTION AND DATA EXTRACTION: All articles were considered for possible inclusion in this review. Abstracts were included only when they were judged to add critical information not otherwise available in the medical literature. DATA SYNTHESIS: L-Asparaginase has been a main component of treatment regimens for acute lymphocytic leukemia. A key limiting factor of L-asparaginase use has been the development of hypersensitivity to the drug. Recently, a polyethylene glycol (PEG) conjugated form of L-asparaginase, pegaspargase, has been made available. PEG modification of L-asparaginase has been shown to alter the tendency of the enzyme to induce an immune response and to extend the half-life of the drug. The majority of patients with hypersensitivity to the native enzyme preparations tolerate pegaspargase without further clinical hypersensitivity. The adverse effect profile of pegaspargase is similar to that of the native forms of L-asparaginase. The recommended dosage of pegaspargase is 2500 IU/m2 administered by intramuscular or intravenous injection every 2 weeks in combination with other chemotherapeutic agents. CONCLUSIONS: Pegaspargase is a safe, effective alternative to L-asparaginase in patients who have had clinical hypersensitivity reactions to both Escherichia coli- and Erwinia carotovora-derived L-asparaginase. However, pegaspargase should not be routinely substituted for L-asparaginase.

Valproate in status epilepticus.

In patients with intractable status epilepticus who have not responded to therapy with benzodiazepines, phenytoin, and barbiturates, valproate may be a reasonable option. Extemporaneously prepared valproate rectal suppositories or retention enemas have been given in dosages of 200-1200 mg q6h in addition to phenytoin, phenobarbital, or both in adults. The pediatric dose used was 15-20 mg/kg, in addition to phenytoin and/or phenobarbital.