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Biomedical subjects

Marc Chamberlain

Publications and source records attributed to Marc Chamberlain.

6 recordsLinked to original sources
PubMed2006

A pharmacokinetic study of intra-CSF administered encapsulated cytarabine (DepoCyt) for the treatment of neoplastic meningitis in patients with leukemia, lymphoma, or solid tumors as part of a phase III study.

INTRODUCTION: Cytarabine liposome injection (DepoCyt), a sterile suspension of the antimetabolite cytarabine, encapsulated into multivesicular, lipid-based particles, has been developed to improve the treatment of neoplastic meningitis (NM) through sustained release of cytarabine. The objective of this study was to determine the pharmacokinetics (PK) of cytarabine after intrathecal administration of 50 mg encapsulated cytarabine (DepoCy) in patients with neoplastic meningitis up to 336 h (14 days) after dosing. METHODS: This was an open-label study wherein two 50-mg doses of DepoCyt were administered 14 days apart via the intraventricular (IVT) route or by lumbar puncture (LP). Cerebrospinal fluid (CSF) samples were collected from eight adult patients at various times up to 14 days after each dose. Plasma samples were also collected within the same time period. CSF samples were analyzed for unencapsulated (free) and encapsulated cytarabine and the cytarabine metabolite, ara-U. Plasma samples were analyzed for free cytarabine and ara-U. The limit of detection was 0.003 microg/mL cytarabine and 0.016 microg/ml for ara-U. RESULTS: The concentration of free and encapsulated cytarabine in the ventricular and lumbar CSF ranged from 0.01 to 1500 microg/mL and were detectable up to 14 days post-dosing. Free cytarabine concentrations in plasma were only sporadically detectable. CSF and plasma concentrations of ara-U were low in all samples. CONCLUSIONS: The administration of intrathecal encapsulation cytarabine prolongs sustained tumor exposure to cytotoxic concentrations of cytarabine (>0.02 microg/ml) with a slow continuous release of cytarabine from the DepoFoam particles, so drug exposure is prolonged over time, resulting in lower peak cytarabine levels and a longer duration of exposure compared with standard cytarabine (Ara-C).

Adult↗
PubMed2006

Ependymomas.

Optimal management of ependymomas includes surgical resection and evaluation of the extent of central nervous system involvement using cerebrospinal fluid cytology and craniospinal contrast-enhanced MRI. In instances of measurable residual disease, reoperation should be considered because survival of patients with ependymomas is significantly improved by performance of a complete resection. In patients not considered for further surgery and with residual disease, limited-field radiotherapy is usually administered. The role of craniospinal irradiation in patients with local disease and no evidence of metastasis is controversial because most tumor recurrences are local and at the site of the primary tumor. No clear role for adjuvant chemotherapy has been demonstrated. When used, chemotherapy for ependymomas has been administered primarily to children aged younger than 3 years as adjuvant therapy and to patients with recurrent disease who are not considered surgical candidates as salvage therapy. Recurrent ependymomas are managed by reoperation of tumors that are surgically accessible, by radiotherapy if not previously administered, and by salvage chemotherapy. The role of stereotactic radiotherapy administered as radiosurgery or brachytherapy is unclear because all reports are anecdotal. Because salvage chemotherapy is not curative, no standard therapy exists, and a variety of chemotherapy agents and drug schedules have been investigated.

Journal Article↗
PubMed2006

Clinical utility and pharmacology of high-dose methotrexate in the treatment of primary CNS lymphoma.

Primary CNS non-Hodgkin lymphoma (PCNSL) has been shown to be increasing in incidence. This appears to be a consequence of the increasing population of those older than 65 years of age in whom PCNSL occurs most often. PCNSL often has a favorable response to treatment and aggressive management may result in extended survival and, in a proportion of patients less than 65 years of age, cure. The majority of neuro-oncologist's advocate utilizing high-dose methotrexate (HD-MTX) as a platform for the chemotherapy treatment of these neoplasms. In this review, the literature regarding HDHMTX as a treatment for PCNSL is summarized as are the pharmacological principles of HD-MTX.

Antimetabolites, Antineoplastic↗
PubMed2005

Leptomeningeal metastases: current concepts and management guidelines.

Neoplastic infiltration of the meninges occurs when malignant cells gain entry into the cerebrospinal fluid (CSF). This is clinically recognized in 4% to 7% of all cancer patients. Leptomeningeal metastases may involve any part of the neural axis via tumor seeding; thus, a multitude of clinical presentations involving one or more domains exist, including the cerebral hemisphere, cranial nerves, and spinal cord and roots. The diagnosis of CSF metastases is often delayed and not appreciated until fixed neurologic deficits become evident. Adequate cytologic analysis of CSF fluid, neuroradiography of brain and spine, and an appropriate clinical context are the key element in diagnosing leptomeningeal metastases. A major challenge of treating neoplastic meningitis is the importance of treating the entire neural axis and stratifying patients in poor risk or good risk categories. Treatment is palliative and involves stabilizing neurologic status and prolonging survival. Median survival for untreated patients is 4 to 6 weeks. Treatment in a broad perspective entails radiotherapy and chemotherapy (systemic and intra-CSF). Commonly used intra-CSF chemotherapy regimens use drugs such as methotrexate, cytarabine, thiotepa, and a sustained-release liposome-encapsulated form of cytarabine (Depocyt, SkyePharma, London, UK). Patients with neoplastic meningitis usually experience a limited survival, even when treated using close adherence to evaluation algorithms and treatment protocols. In randomized controlled clinical trials using currently available intra-CSF chemotherapeutic agents, median survival in carefully selected, study-eligible groups of patients was 2 to 6 months.

Algorithms↗
PubMed2003

Temozolomide as an alternative to irradiation for elderly patients with newly diagnosed malignant gliomas.

BACKGROUND: The optimal treatment for elderly patients (defined as patients 70 years of age or older) with malignant gliomas (MG) remains controversial. Some physicians advocate withholding therapy following diagnosis based on the observation that elderly patients do not tolerate adjuvant radiotherapy. The availability of temozolomide (TMZ), a new alkylating agent with antiglioma efficacy, offers another potential therapeutic option for these patients. The drug can be administered orally at home with minimal morbidity. METHODS: The authors retrospectively reviewed a cohort of 86 consecutive elderly MG patients from three institutions, 32 of whom received monthly TMZ in lieu of radiation. RESULTS: Initial Karnofsky performance score was the only predictor of survival in this cohort. No difference in survival was noted between these two groups. Toxicity was minimal in the chemotherapy-treated group and a higher percentage of patients receiving chemotherapy died at home. CONCLUSIONS: The authors concluded that TMZ is as effective as irradiation as a treatment of elderly patients with MG. It is an alternative and, perhaps, a superior therapeutic option to irradiation, based on its ease of administration and low morbidity.

Administration, Oral↗