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Biomedical subjects

S M Blaney

Publications and source records attributed to S M Blaney.

43 records · Page 3Linked to original sources
PubMed1991

Current pharmacological treatment approaches to central nervous system leukaemia.

Significant advances in the treatment and prevention of meningeal leukaemia have been made in the past 3 decades. This progress has resulted from the development of innovative approaches to treatment as well as a better understanding of the pharmacokinetics and pharmacodynamics of the commonly used antileukaemic agents. Intrathecal therapy, via the intralumbar or intraventricular route, is a form of regional therapy that results in the delivery of very high drug concentrations to the principle target tumour site (the meninges) using a relatively small drug dose, thereby minimising both systemic drug exposure and systemic toxicity. The dosage and schedules, clinical pharmacology and toxicities of the commonly used intrathecal agents, methotrexate and cytarabine (cytosine arabinoside; Ara-C) are discussed in detail. Another approach which has been used to overcome the poor penetration of antileukaemic drugs into the CNS has been the use of high-dose systemic therapy. This strategy has been successfully applied in the treatment of meningeal leukaemia using both high-dose methotrexate and high-dose cytarabine. The clinical pharmacology, toxicities, and potential limitations of this approach are outlined. Finally, new agents that are currently undergoing clinical evaluation and future directions for research are also discussed.

Adolescent↗
PubMed1991

Pharmacologic approaches to the treatment of meningeal malignancy.

The meninges are a unique site of recurrence for certain malignancies because of the limited penetration of systemically administered cytotoxic drugs across the blood-brain barrier. While this phenomenon was first recognized in children with acute lymphoblastic leukemia, a similar pattern is also occurring in breast cancer, ovarian cancer, and small cell lung cancer. Recognition of the limitations of standard systemic antileukemic therapy for the treatment of meningeal disease led to the development of new therapeutic strategies targeted directly at the CNS. These include intralumbar therapy using methotrexate or cytarabine, intraventricular chemotherapy, and high-dose systemic drug administration. New agents showing promise are intrathecal diaziquone, 6-mercaptopurine, and mafosfamide.

Adolescent↗
PubMed1990

Pharmacokinetics and metabolism of cyclopentenyl cytosine in nonhuman primates.

The plasma and cerebrospinal fluid pharmacokinetics of cyclopentenyl cytosine (CPE-C) were studied following i.v. bolus and continuous i.v. infusion in male rhesus monkeys. Following an i.v. bolus dose of 100 mg/m2 plasma elimination of CPE-C was biexponential with a mean t1/2 alpha of 8.4 min, a mean t1/2 beta of 36 min, and a total clearance (CLTB) of 662 ml/min/m2, which is 5- to 10-fold higher than clearance rates in rodents and dogs. Less than 20% of the total dose of CPE-C was excreted unchanged in the urine. The remainder was excreted as the inactive deamination product cyclopentenyl uridine (CPE-U). The ratio of the areas under the plasma concentration versus time curves of CPE-U to CPE-C was 7.0 +/- 2.4 following i.v. bolus CPE-C. The cerebrospinal fluid:plasma ratios of CPE-C and CPE-U were 0.08 and 0.30, respectively. Continuous i.v. infusion of CPE-C was compared to continuous infusion of 1-beta-D-arabinofuranosylcytosine in two monkeys. Steady state plasma concentrations, normalized to a dose of 12.5 mg/m2/h of CPE-C and an equimolar dose of 1-beta-D-arabinofuranosylcytosine, were 2.1 and 0.53 microM, respectively. The steady state concentrations of their corresponding uridine metabolites (CPE-U and 1-beta-D-arabinofuranosyluridine) were 8.2 and 15.5 microM. The rapid elimination of CPE-C by deamination in the primate resulted in a much higher CLTB and considerably lower total drug exposure than in rodents and dogs that clear CPE-C at a much lower rate by renal excretion. These significant interspecies differences in the disposition of CPE-C should be considered in the selection of a starting dose and schedule for human trials and suggest that a pharmacologically directed dose escalation scheme should be used in the planned phase I studies.

Animals↗
PubMed1989

Survival after isolated cerebral mucormycosis.

Cerebral mucormycosis is a rare disorder caused by several genera of the family Mucoraceae. The genera Rhizopus, Absidia, and Mucor are the predominant pathogenic groups. Disease caused by these organisms usually complicates an underlying chronic illness, such as diabetes mellitus or malignancy. Cerebral involvement usually occurs from an ascending infection from the paranasal sinuses via the orbit and is usually associated with poorly controlled diabetes. The pulmonary system is the most common site of infection in patients with leukemia. Isolated cerebral mucormycosis not associated with head trauma or intravenous drug abuse is a rare disorder. We report what we believe to be the first successfully treated case of isolated cerebral mucormycosis in a patient with acute lymphocytic leukemia in remission.

Adolescent↗
PubMed1985

Osteolysis in cat-scratch fever.

The osteolysis associated with cat-scratch fever resembles more ominous conditions. The combination of osteolysis and unilateral regional adenopathy in a child or adolescent should suggest cat-scratch disease.

Adolescent↗
PubMedDate not supplied

Phase II trial of pyrazoloacridine in children with solid tumors: a Pediatric Oncology Group phase II study.

PURPOSE: Pyrazoloacridine (PZA), a rationally synthesized deoxyribonucleic acid (DNA) binding agent that preferentially inhibits ribonucleic acid rather than DNA synthesis, is active against hypoxic and noncycling tumor cells and has greater in vitro activity against a broad range of human solid tumor lines than against the L1210 murine leukemia line. The Pediatric Oncology Group conducted a phase II study to determine the activity of PZA administered as a 3-hour infusion. PATIENTS AND METHODS: The activity of PZA was evaluated in patients with a variety of childhood solid tumors including rhabdomyosarcoma, Ewing sarcoma/peripheral neuroectodermal tumor, neuroblastoma, osteogenic sarcoma, Wilms tumor, or other solid tumors (excluding brain tumors). In addition to a standard three-stage design to test the drug's activity in each tumor type, a global stopping rule was used such that if no complete or partial responses (CR or PR) occurred in the first 35 patients (pooled across all strata except "other"), the study would be closed. RESULTS: A total of 47 patients were entered into the study. Myelosuppression was the primary toxicity. Severe nonhematologic toxicity was uncommon. Only one patient exhibited grade 3 neurologic toxicity (anxiety). No CRs or PRs were observed. CONCLUSION: Use of the global stopping criterion permitted early identification of lack of activity of PZA against childhood solid tumors.

Acridines↗