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Biomedical subjects

M C Chamberlain

Publications and source records attributed to M C Chamberlain.

At least 55 records · Page 3Linked to original sources
PubMed1995

Concurrent cisplatin therapy and iodine 125 brachytherapy for recurrent malignant brain tumors.

OBJECTIVE: Toxicity and safety study of concurrent cisplatin therapy and iodine 125 (125I) brachytherapy. BACKGROUND: Iodine 125 brachytherapy has an established role in surgically accessible recurrent tumors of brain. Cisplatin has antitumoral activity against glial neoplasms and has demonstrated sensitization of tumor to radiotherapy. DESIGN/METHODS: In 16 patients (age range, 13 to 68 years, median, 47 years), stereotactically placed catheters were afterloaded with 125I sources. A median 50-Gy minimum treatment volume dose was delivered during a 100-hour period along with cisplatin (20 mg/m2 per day for 5 days). Histologic diagnoses included glioblastoma multiforme (n = 11), anaplastic astrocytoma (n = 3), ependymoma (n = 1), and anaplastic oligodendroglioma (n = 1). Tumor volumes ranged from 7.0 to 73 cm3 (median, 25 cm3). RESULTS: Early complications included headache (n = 7), transient exacerbations of preexisting neurologic deficits (n = 5), seizures (n = 3), and nausea/vomiting (n = 3). Late complications included steroid dependency (n = 10), progressive dementia in the absence of recurrent tumor (n = 1), and radiation-induced necrosis (n = 9) requiring reoperation (n = 9). Fifteen of 16 patients were assessable, with a median follow-up time of 9.5 months. Brachytherapy was discontinued in one patient owing to an acute subdural hematoma. A partial response was seen in five patients, disease remained stable in seven patients, and disease progressed in three patients. CONCLUSIONS: We conclude that 125I brachytherapy with concurrent cisplatin therapy is associated with an acceptable level of toxic effects and warrants further investigation.

Adolescent↗
PubMed1995

Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide.

BACKGROUND: Chiasmatic-hypothalamic gliomas are not amenable to surgical resection and therefore are treated with either radiotherapy or chemotherapy. Etoposide (VP-16), administered on a long-term oral schedule, represents a novel chemotherapeutic approach. PATIENTS AND METHODS: Fourteen patients (age range, 2 to 15 years) were treated with etoposide following tumor progression as determined by clinical and neuroradiographic examinations. Thirteen patients had received prior radiotherapy, and 12 received prior nitrosourea-based chemotherapy. Etoposide was administered orally; each cycle consisted of 50 mg/m2 per day on days 1 to 21 and days 36 to 57. Clinical and neuroradiographic examinations were performed from days 58 to 72 prior to the start of each cycle of therapy. Complete blood cell counts were performed weekly. RESULTS: Treatment-related complications included partial alopecia (n = 7), diarrhea (n = 6), weight loss (n = 5), neutropenia (n = 4), and thrombocytopenia (n = 4). Three patients required a transfusion (ie, red blood cell [n = 3] and platelet [n = 2] transfusions), and one patient required antibiotic treatment of neutropenic fever. There were no treatment-related deaths. Fourteen patients were evaluable; in eight of these 14 patients, a response was demonstrated radiographically (complete response [n = 1], partial response [n = 4], and stable disease [n = 3]), with a median duration of response of 8 months. CONCLUSIONS: Long-term treatment with oral etoposide was well tolerated by the patients in this study, and etoposide was a relatively nontoxic chemotherapeutic agent with apparent activity in this small cohort of patients who had recurrent chiasmatic-hypothalamic gliomas.

Administration, Oral↗
PubMed1995

Pharmacokinetics of intralumbar DTC-101 for the treatment of leptomeningeal metastases.

PURPOSE: To study the results of intralumbar administration of chemotherapeutic agents for the treatment of neoplastic meningitis and to determine how these results relate to the variable and often subtherapeutic drug concentrations in the ventricular cerebrospinal fluid (CSF) compartment. Ventricular and lumbar pharmacokinetic studies were done following intralumbar administration of DTC-101, an extended-release formulation of cytarabine. PATIENTS AND METHODS: Nine patients (age range, 23 to 67 years; median age, 42 years) with leptomeningeal metastases were treated with 18 courses of intralumbar DTC-101. Eight patients who were treated with 14 courses underwent pharmacokinetic CSF sampling from the lumbar sac and lateral ventricle. Cytarabine concentrations were determined by using high-pressure liquid chromatography. RESULTS: Following intralumbar administration of DTC-101, therapeutic free cytarabine concentrations were achieved rapidly in both of the ventricular and lumbar CSF compartments and maintained for 2 weeks. The mean pharmacokinetic parameters of free cytarabine in the lumbar and ventricular CSF compartments were as follows: maximum concentration, 226 and 6.06 mg/L; half-life, 277 and 130 hours; and area under the concentration vs time curve, 4120 and 598 micrograms/h per milliliter, respectively. CONCLUSIONS: Intralumbar administration of DTC-101 results in extended cytotoxic free cytarabine concentrations in both of the lumbar and ventricular regions of CSF and allows an every-other-week drug-dosing schedule.

Adult↗
PubMed1995

Spinal 111Indium-DTPA CSF flow studies in leptomeningeal metastasis.

Sixteen consecutive patients (8 men; 8 women; age range 6-63 years, median 40 years) with leptomeningeal metastasis were found by radionuclide ventriculography to have cerebrospinal fluid (CSF) flow interruption at the following sites: cisterna magna/basal cisterns (6); cervical (5) and thoracic (3) spinal subarachnoid space. Two additional patients had no evidence of interruption of CSF flow. All patients underwent intralumbar injection of 111Indium-DTPA and imaging of spinal ascent of radionuclide, corroborating sites of CSF flow disruption seen by radionuclide ventriculography. Median (range) time to appearance in lumbar, thoracic and cervical spinal subarachnoid compartments were 1 (1), 22.5 (20-25) and 32.5 (30-35) minutes respectively. Appearance of radionuclide in the cisterna magna/basal cisterns, sylvian cisterns, ventricular system and high cerebral convexity was 37.5 (35-40), 65 (60-70), 1440 (1440) and 1440 (1440) minutes respectively. Only 1 of 8 patients with interruption of CSF flow within the spinal subarachnoid space shown by intralumbar radionuclide flow study, was seen by either CT myelography or contrast enhanced spine MR to have CSF flow block. No patient with base of brain block (0/6) shown by radionuclide CSF flow studies demonstrated CSF flow disruption by either cranial contrast enhanced CT or MR. In conclusion, spinal 111In-DTPA CSF flow studies confirmed sites of CSF flow block shown by radionuclide ventriculography and demonstrate the feasibility of assessing CSF compartmentalization by intralumbar radionuclide administration. Furthermore, radionuclide CSF flow studies when compared to conventional neuroradiographic imaging are more sensitive in demonstrating interruption of CSF flow.

Adult↗
PubMed1995

Comparative spine imaging in leptomeningeal metastases.

Sixty-one patients (34 men; 27 women) ranging in age from 1-74, median 40 years with leptomeningeal metastases (LM) as defined by either positive CSF cytology (85%) or a clinical syndrome and compatible neuroradiographic findings (15%) underwent CT-myelographic (CT-M), spine MR (S-MR) and 111Indium-DTPA CSF flow studies (FS). Each patient underwent sequential spine imaging (CT-M, S-MR and FS) over a median of 5 days. In 57% of patients, all 3 spine imaging modalities were normal. 43% of patients demonstrated abnormalities on spine imaging; 33% had abnormal FS, 34% showed abnormalities on S-MR and 33% had abnormalities by CT-M. FS were most sensitive for detecting interruption of CSF flow whereas CT-M and S-MR better demonstrated nerve root thickening (CT-M approximately S-MR), cord enlargement (CT-M > S-MR), subarachnoid nodules (S-MR > CT-M), intraparenchymal cord tumor (S-MR > CT-M) and epidural spinal cord compression (S-MR = CT-M). In conclusion, patients with LM frequently require spine imaging and the results of this study suggest both S-MR and FS provide the best radiographic assessment wherein S-MR is superior for detecting bulky disease and FS best demonstrates interruption of CSF flow.

Adolescent↗
PubMed1995

A review of leptomeningeal metastases in pediatrics.

Leptomeningeal metastasis is an uncommon problem in pediatric neurology and oncology. It occurs primarily in children with acute lymphoblastic leukemia and primary brain tumors. Although leptomeningeal metastasis may present with focal neurologic signs and symptoms, leptomeningeal metastasis is a disease affecting the entire neuraxis and necessitating an extent-of-disease evaluation of both the brain and spinal cord. Neuroradiographic staging of leptomeningeal metastases includes contrast-enhanced cranial computed tomography, magnetic resonance imaging, contrast-enhanced spine magnetic resonance imaging or computed tomographic myelography, and radionuclide cerebrospinal fluid flow studies. As a consequence of global neuraxis involvement, the treatment of leptomeningeal metastases requires therapy directed at all cerebrospinal fluid compartments. The treatment of leptomeningeal metastases usually includes both radiotherapy and intra-cerebrospinal fluid drug therapy. Radiotherapy is directed to regions of bulky or symptomatic central nervous system disease. Intra-cerebrospinal fluid drug therapy, using one of three available chemotherapeutic agents (methotrexate, cytarabine, or triethylene thiophosphoramide), is administered by a variety of schedules and either by intralumbar or intraventricular drug delivery. Notwithstanding that the treatment of leptomeningeal metastases is palliative, with an expected patient survival of 6 months, it often affords stabilization and protection from further neurologic deterioration in children with leptomeningeal metastases in whom death is usually a consequence of progressive systemic or parenchymal brain disease.

Antineoplastic Agents↗
PubMed1995

Salvage chemotherapy with paclitaxel for recurrent primary brain tumors.

PURPOSE: To assess the safety and efficacy of Taxol (paclitaxel; Bristol-Myers Squibb Co, Princeton, NJ) given at a dose of 175 mg/m2 every 3 weeks as a 3- to 4-hour outpatient infusion to patients with recurrent malignant primary brain tumors who had received prior radiotherapy and at least one chemotherapy regimen containing nitrosoureas and who were no longer responding to therapy. PATIENTS AND METHODS: Twenty patients (12 men and eight women), ages 19 to 69 years (median, 35), with recurrent primary brain tumors were treated according to a phase II protocol with intravenous Taxol. Tumor histologies included the following: anaplastic astrocytoma (n = 8), glioblastoma multiforme (n = 8), and anaplastic oligodendroglioma (n = 4). All patients had been previously treated with subtotal resection, limited-field radiotherapy (median dose, 60 Gy; range, 54 to 78 Gy), and nitrosourea-based chemotherapy. Taxol was administered intravenously at a dose of 175 mg/m2/d every 3 weeks with neurologic and neuroradiographic evaluation every 8 to 9 weeks. Complete blood cell counts were performed weekly. RESULTS: A median of six cycles of Taxol (range, two to 12) were administered to 20 assessable patients. Toxicities included partial alopecia (n = 10), thrombocytopenia (n = 4), rate of Taxol administration-dependent bradycardia (n = 3), and nondisabling peripheral neuropathy (n = 1). No patient developed neutropenic fever or sepsis or required cytokine support. Two patients required blood-product support (platelet transfusions in both). Four patients (20%) demonstrated a partial response (PR) and seven (35%) had stable disease (SD) for a total response plus SD rate of 55%. The median time to tumor progression was 6 months (range, 2 to 20). CONCLUSION: Taxol demonstrated modest efficacy with minimal toxicity in this heavily pretreated cohort of young patients with recurrent primary brain tumors.

Adult↗
PubMed1995

Recurrent chiasmatic-hypothalamic glioma treated with oral etoposide.

PURPOSE: Chiasmatic-hypothalamic gliomas are not amenable to surgical resection and therefore are treated with either radiotherapy or chemotherapy. Here we report the use of etoposide (VP-16) administered on a chronic oral schedule as a novel chemotherapeutic approach. PATIENTS AND METHODS: Fourteen patients, aged 2 to 15 years, were treated with VP-16 after clinical and neuroradiographic tumor progression. Thirteen patients had received prior radiotherapy, and 12 received prior nitrosourea-based chemotherapy. VP-16 was administered orally, each cycle consisting of 50 mg/m2/d on day 1 through 21 and 36 through 57. Clinical and neuroradiographic evaluations were performed during days 58 through 72 before initiation of each cycle of therapy. Complete blood counts were performed weekly. RESULTS: Treatment-related complications included the following: partial alopecia (seven patients); diarrhea (six); weight loss (five); neutropenia (four); and thrombocytopenia (four). Three patients required transfusion (three RBC; two platelet), and one patient required antibiotic treatment of neutropenic fever. There were no treatment-related deaths. Fourteen patients were assessable, five of whom demonstrated a radiographic response (one complete and four partial); and three patients demonstrated stable disease, with a median duration of response of 8 months. CONCLUSION: Chronic oral VP-16 is well tolerated, produces modest toxicity, and has apparent activity in this small cohort of patients with recurrent chiasmatic-hypothalamic gliomas.

Administration, Oral↗
PubMed1995

Primary CNS lymphoma.

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Central Nervous System Neoplasms↗
PubMed1995

CNS lymphoma.

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Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Gliomas in patients with acquired immune deficiency syndrome.

BACKGROUND: Ten percent of patients with acquired immune deficiency syndrome (AIDS) have intracerebral mass lesions of which the majority are due either to toxoplasmosis or primary central nervous system lymphomas. METHODS: Three patients with AIDS presented with solitary intracerebral mass lesions and were found by pathologic examination to have gliomas. RESULTS: After surgery, all patients were treated with radiotherapy and procarbazine, comustine, and vincristine multiagent chemotherapy. Median follow-up is 12 months. CONCLUSIONS: Occasionally, patients with AIDS and intracerebral mass lesions have primary nonlymphomatous brain tumors, an occurrence not related clearly to underlying immunoincompetence.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Stereotactic radiosurgery for recurrent gliomas.

BACKGROUND: The treatment of recurrent gliomas is palliative; however, the local pattern of tumor recurrence permits retreatment with single fraction, high dose stereotactic radiotherapy or radiosurgery (RS). METHODS: Twenty patients (median Karnofsky performance status, 80), aged 8-62 years with recurrent gliomas, were treated with RS after failing adjuvant therapy. Tumor histologies included glioblastoma multiforme (5), anaplastic astrocytoma (10), fibrillary astrocytoma (4), and primitive neuroectodermal tumor (1). Tumor volumes ranged from 3-53.5 cc, with a median of 17 cc. RESULTS: Seven early and one late radiation complication were seen. All seven early radiation complications were due to raised intracranial pressure and resolved in all but one patient who died. Median follow-up in 19 evaluable patients was 8 months (range, 2-29 months). Fourteen patients died from progressive tumor (median survival, 7 months). Five patients, four with recurrent tumor, were alive (median follow-up, 19 months) with a median time-to-tumor progression of 9 months. CONCLUSIONS: Radiosurgery demonstrates modest efficacy with acceptable toxicity in selected patients with recurrent gliomas and warrants further investigation.

Adolescent↗
PubMed1994

Long survival in patients with acquired immune deficiency syndrome-related primary central nervous system lymphoma.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is the most common brain tumor occurring in patients with acquired immune deficiency syndrome (AIDS). After diagnosis of PCNSL, the median survival time is 2-5 months with treatment with whole brain irradiation (WBI). METHODS: Four (of approximately 40) patients with AIDS and PCNSL seen by the University of California, San Diego (UCSD) Neuro-Oncology service were treated with multimodal therapy, including WBI with hydroxyurea, followed by 3 cycles of procarbazine/lomustine/vincristine (PCV) chemotherapy. RESULTS: Survival after tumor diagnosis ranged from 11 to 16 months, with a median of 13.5 months. CONCLUSION: Selected patients with AIDS and PCNSL may have long survival when treated with multimodal therapy.

Adult↗
PubMed1994

New approaches to and current treatment of leptomeningeal metastases.

Leptomeningeal metastases (LM), a common problem in neurooncology, occur in approximately 5% of all patients with cancer. Aside from frequent focal signs and symptoms, LM affects the entire neuraxis; therefore, staging and treatment must encompass all cerebrospinal fluid compartments. Central nervous system staging of LM includes contrast-enhanced cranial computed tomography or magnetic resonance imaging, contrast-enhanced spine magnetic resonance imaging or computed tomographic myelography, and radionuclide cerebrospinal fluid flow study. Treatment of LM includes involved-field radiotherapy of bulky or symptomatic disease and intracerebrospinal fluid drug therapy. At present, intracerebrospinal fluid drug therapy is confined to three chemotherapeutic agents (methotrexate, cytosine arabinoside, and thiotepa) and is administered in a variety of schedules by either intralumbar or intraventricular drug delivery. Although treatment of LM is palliative, with an expected median patient survival of 6 months, it often provides stabilization and protection from further neurologic deterioration in patients with LM.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1994

Pediatric leptomeningeal metastasis: 111In-DTPA cerebrospinal fluid flow studies.

Nine children (five girls and four boys) ranging in age from 1 to 18 years (median age, 12 years) with leptomeningeal metastasis were evaluated for cerebrospinal fluid compartmentalization with cerebrospinal fluid flow studies using ventricular diethylenetriaminepentaacetic acid labeled with indium 111 (111In-DTPA). Histologic diagnosis included medulloblastoma (two), primitive neuroectodermal tumor (two), acute lymphoblastic leukemia (two), pineoblastoma (one), ependymoma (one), and anaplastic astrocytoma (one). Sixteen 111In-DTPA cerebrospinal fluid flow studies were performed, of which nine demonstrated normal anterograde cerebrospinal fluid flow of radionuclide, with the following cerebrospinal fluid compartment median times to appearance, with ranges in parentheses: ventricles, 1 minute (0 to 3 minutes); cisterna magna/basal cisterns, 5 minutes (3 to 5 minutes); cervical subarachnoid space, 8 minutes (5 to 10 minutes); thoracic subarachnoid space, 15 minutes (10 to 30 minutes); lumbar subarachnoid space, 35 minutes (20 to 45 minutes); and sylvian cistern, 80 minutes (60 to 90 minutes). Blockage of normal anterograde cerebrospinal fluid flow was seen in seven 111In-DTPA cerebrospinal fluid flow studies in the following cerebrospinal fluid compartments: cervical subarachnoid space (four), lumbar subarachnoid space (two), and cisterna magna/basal cisterns (one). Five 111In-DTPA cerebrospinal fluid flow studies were performed after demonstration of cerebrospinal fluid compartmentalization and treatment with limited-field radiation therapy to involved regions; cerebrospinal fluid flow blocks resolved in three. In conclusion, cerebrospinal fluid compartmentalization, as shown by radionuclide ventriculography, is a common occurrence in pediatric leptomeningeal metastasis (four of nine patients, or 44%) and may be palliated by involved-field radiotherapy.

Adolescent↗
PubMed1993

Treatment of leptomeningeal metastasis with intraventricular administration of depot cytarabine (DTC 101). A phase I study.

Depo cytarabine (DTC 101 [formerly identified as Depo/Ara-C]) is a slow-releasing, depot formulation in which cytarabine is encapsulated within the aqueous compartments of microscopic (DepoFoam) particles. A phase I trial of DTC 101, given intraventricularly, was conducted in patients with leptomeningeal metastasis. Nine patients were given 1 to 7 cycles of DTC 101 in doses ranging from 25 to 125 mg that were administered via an Ommaya reservoir into the lateral ventricle. The dose-limiting toxic reaction was encephalopathy that occurred at the 125-mg dose level. All toxic episodes but one were transient and reversible, with the total duration of toxicity lasting from 1 to 7 days. The ventricular concentration of free cytarabine released from DTC 101 into cerebrospinal fluid decreased biexponentially with an initial half-life of 7.2 +/- 1.7 (+/- SEM) hours and a terminal half-life of 140 +/- 49 hours. The cerebrospinal fluid was cleared of malignant cells within 3 weeks of initial therapy in five of six cytologically evaluable patients. The duration of response ranged from 2 to more than 14 weeks, with a median of over 11 weeks. In conclusion, DTC 101 appears to be a pharmacologically attractive agent for use against leptomeningeal metastasis. The toxic episodes that occur with this therapy are well tolerated by patients.

Adult↗