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Biomedical subjects

T Batchelor

Publications and source records attributed to T Batchelor.

10 recordsLinked to original sources
PubMed2001

Intrathecal treatment of neoplastic meningitis due to breast cancer with a slow-release formulation of cytarabine.

DepoCyte is a slow-release formulation of cytarabine designed for intrathecal administration. The goal of this multi-centre cohort study was to determine the safety and efficacy of DepoCyte for the intrathecal treatment of neoplastic meningitis due to breast cancer. DepoCyte 50 mg was injected once every 2 weeks for one month of induction therapy; responding patients were treated with an additional 3 months of consolidation therapy. All patients had metastatic breast cancer and a positive CSF cytology or neurologic findings characteristic of neoplastic meningitis. The median number of DepoCyte doses was 3, and 85% of patients completed the planned 1 month induction. Median follow up is currently 19 months. The primary endpoint was response, defined as conversion of the CSF cytology from positive to negative at all sites known to be positive, and the absence of neurologic progression at the time the cytologic conversion was documented. The response rate among the 43 evaluable patients was 28% (CI 95%: 14-41%); the intent-to-treat response rate was 21% (CI 95%: 12-34%). Median time to neurologic progression was 49 days (range 1-515(+)); median survival was 88 days (range 1-515(+)), and 1 year survival is projected to be 19%. The major adverse events were headache and arachnoiditis. When drug-related, these were largely of low grade, transient and reversible. Headache occurred on 11% of cycles; 90% were grade 1 or 2. Arachnoiditis occurred on 19% of cycles; 88% were grade 1 or 2. DepoCyte demonstrated activity in neoplastic meningitis due to breast cancer that is comparable to results reported with conventional intrathecal agents. However, this activity was achieved with one fourth as many intrathecal injections as typically required in conventional therapy. The every 2 week dose schedule is a major advantage for both patients and physicians.

Adult↗
PubMed2000

Cytotoxic chemotherapy: advances in delivery, pharmacology, and testing.

Adjuvant treatment of malignant gliomas, the most common types of primary brain tumors, with intravenous (iv) chemotherapy has not significantly improved survival for patients with these forms of cancer. A major factor in the failure of iv chemotherapy is the blood-brain barrier (BBB), a physiologic impediment to the delivery of cytotoxic chemotherapeutic drugs to the central nervous system (CNS). Intra-arterial and intrathecal infusion, blood-brain barrier disruption, high-dose chemotherapy, intratumoral administration, and convection-enhanced delivery are methods developed to overcome the BBB. Although some of these methods may increase the local concentration-time profile, improvement in clinical outcomes has yet to be definitively established. New methods for assessment of drug delivery to the brain tumor will assume increasing importance in the study of new cytotoxic chemotherapeutic drugs for these types of cancer. Pharmacokinetic studies are critical components of these clinical trials and allow assessment of drug delivery to the CNS and brain tumor. Additionally, pharmacokinetic studies will remain an important component of early clinical trials, particularly for identifying significant drug interactions involving the various supporting medications that are typically used in this patient population.

Antineoplastic Agents↗
PubMed1999

Ma1, a novel neuron- and testis-specific protein, is recognized by the serum of patients with paraneoplastic neurological disorders.

The identification of antineuronal antibodies has facilitated the diagnosis of paraneoplastic neurological disorders and the early detection of the associated tumours. It has also led to the cloning of possibly important neuron-specific proteins. In this study we wanted to identify novel antineuronal antibodies in the sera of patients with paraneoplastic neurological disorders and to clone the corresponding antigens. Serological studies of 1705 sera from patients with suspected paraneoplastic neurological disorders resulted in the identification of four patients with antibodies that reacted with 37 and 40 kDa neuronal proteins (anti-Ma antibodies). Three patients had brainstem and cerebellar dysfunction, and one had dysphagia and motor weakness. Autopsy of two patients showed loss of Purkinje cells, Bergmann gliosis and deep cerebellar white matter inflammatory infiltrates. Extensive neuronal degeneration, gliosis and infiltrates mainly composed of CD8+ T cells were also found in the brainstem of one patient. In normal human and rat tissues, the anti-Ma antibodies reacted exclusively with neurons and with testicular germ cells; the reaction was mainly with subnuclear elements (including the nucleoli) and to a lesser degree the cytoplasm. Anti-Ma antibodies also reacted with the cancers (breast, colon and parotid) available from three anti-Ma patients, but not with 66 other tumours of varying histological types. Preincubation of tissues with any of the anti-Ma sera abrogated the reactivity of the other anti-Ma immunoglobulins. Probing of a human complementary DNA library with anti-Ma serum resulted in the cloning of a gene that encodes a novel 37 kDa protein (Mal). Recombinant Mal was specifically recognized by the four anti-Ma sera but not by 337 control sera, including those from 52 normal individuals, 179 cancer patients without paraneoplastic neurological symptoms, 96 patients with paraneoplastic syndromes and 10 patients with non-cancer-related neurological disorders. The expression of Mal mRNA is highly restricted to the brain and testis. Subsequent analysis suggested that Mal is likely to be a phosphoprotein. Our study demonstrates that some patients with paraneoplastic neurological disorders develop antibodies against Mal, a new member of an expanding family of 'brain/testis' proteins.

Amino Acid Sequence↗
PubMed1999

Randomized trial of a slow-release versus a standard formulation of cytarabine for the intrathecal treatment of lymphomatous meningitis.

PURPOSE: To evaluate the efficacy and safety of a slow-release formulation of cytarabine (DepoCyt; Chiron Corp, Emeryville, CA, and Skye Pharma, Inc, San Diego, CA) that maintains cytotoxic concentrations of cytarabine (ara-C) in the CSF of most patients for more than 14 days. PATIENTS AND METHODS: Twenty-eight patients with lymphoma and a positive CSF cytology were randomized to receive DepoCyt 50 mg once every 2 weeks or free ara-C 50 mg twice a week for 1 month. Patients whose CSF cytology converted to negative and who did not have neurologic progression received an additional 3 months of consolidation therapy and then 4 months of maintenance therapy. All patients received dexamethasone 4 mg orally bid on days 1 through 5 of each 2-week cycle. RESULTS: The response rate was 71% for DepoCyt and 15% for ara-C on an intent-to-treat basis (P =.006). All of the patients on the DepoCyt arm but only 53% of those on the ara-C arm were able to complete the planned 1-month induction therapy regimen. Time to neurologic progression and survival trend in favor of DepoCyt (median, 78.5 v 42 days and 99.5 v 63 days, respectively; P >.05). DepoCyt treatment was associated with an improved mean change in Karnofsky performance score at the end of induction (P =.041). The major adverse events on both arms were headache and arachnoiditis, which were often caused by the underlying disease. CONCLUSION: DepoCyt injected once every 2 weeks produced a high response rate and a better quality of life as measured by Karnofsky score relative to that produced by free ara-C injected twice a week.

Adult↗
PubMed1998

Neurologic emergencies in cancer patients.

Neurologic emergencies are common among cancer patients and their incidence is increasing as patients live longer as a result of improved antineoplastic therapy. This article reviews acute neurologic complications in cancer patients. Among those complications reviewed are brain metastases, epidural spinal cord compression, leptomeningeal metastases, cerebrovascular disorders, complications of antineoplastic therapy, and paraneoplastic syndromes.

Antineoplastic Agents↗
PubMed1996

Medical management of cerebral metastases.

Brain edema, seizures, and venous thromboembolism are frequently encountered complications of cerebral metastases that result in increased morbidity and mortality. Effective medical management of these complications with steroids, anticonvulsants, and anticoagulants can result in symptomatic improvement and a better quality of life for these patients. However, these medical therapies should be administered only when indicated as each is associated with potentially serious toxicity.

Anticoagulants↗