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Marc C Chamberlain

Publications and source records attributed to Marc C Chamberlain.

12 recordsLinked to original sources
PubMed2003

Quality-of-life-adjusted survival comparison of sustained-release cytosine arabinoside versus intrathecal methotrexate for treatment of solid tumor neoplastic meningitis.

BACKGROUND: The authors compared the quality of life of patients with solid tumor neoplastic meningitis treated in a controlled trial that compared conventional intrathecal methotrexate with a depot cytosine arabinoside liposomal injection (DepoCyt). The authors evaluated the trade-off between toxicity and improved clinical outcome. METHODS: Quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis was used to evaluate data collected prospectively from a randomized clinical trial that compared DepoCyt with methotrexate. Sixty-one patients with confirmed solid tumor neoplastic meningitis were randomized to receive either methotrexate or DepoCyt. RESULTS: Within the 12-month follow-up, the average patient in the DepoCyt arm (compared with the methotrexate arm) achieved 71 more days of neurologic progression-free survival and 52 more days of overall survival, but experienced slightly more days with toxicity. The DepoCyt regimen provided greater quality-adjusted survival regardless of the quality-of-life valuations placed on time with toxicity and time following disease progression (range, 44-79 days). This gain was significant (P < 0.05) for all patients except for those who placed a high relative value on time following disease progression. CONCLUSIONS: The clinical benefits of DepoCyt offset a trend toward additional toxicity among patients with sold tumor neoplastic meningitis. The magnitude of the benefit depends on how the patient values time spent in toxicity and disease progression. The results of this analysis can be used at the bedside to make evidence-based individual treatment decisions.

Adult↗
PubMed2003

Ependymomas.

Ependymomas are uncommon neoplasms of the central nervous system (CNS), and as a consequence, few randomized, clinical trials have been performed, thereby limiting treatment guidelines. A review of the literature would permit the following conclusions regarding treatment. The best management of newly diagnosed ependymoma entails a complete resection corroborated by postoperative contrast-enhanced magnetic resonance imaging (MRI). If an incomplete resection is documented, a second attempt at gross total resection should be considered, given the prognostic significance of complete resection. Small volume residual disease is best managed with involved-field radiotherapy unless postoperative staging (cerebrospinal fluid cytology, neuraxis MRI) documents metastatic disease, which is best managed by craniospinal irradiation. The role of chemotherapy is uncertain and in general would be reserved for patients having previously failed surgery and radiotherapy. Disease-free survival following recurrence is unusual (<15% at 5 years) and suggests intensification of initial adjuvant treatment may best prevent relapse.

Adult↗
PubMed2003

Systemic chemotherapy, intrathecal chemotherapy, and symptom management in the treatment of leptomeningeal metastasis.

Metastasis to the leptomeninges occurs in many common cancers, including leukemia; lung, breast, and gastrointestinal cancers; and tumors of the brain. By way of the flow of cerebrospinal fluid, leptomeningeal metastasis spreads throughout the neuraxis. Consequently, therapy for leptomeningeal metastasis must be directed to the entire central nervous system (CNS). Treatment often consists of involved-field radiotherapy, systemic chemotherapy, and intrathecal chemotherapy. However, because meningeal spread occurs most often in advanced disease, treatment is mainly palliative, except in childhood leukemia, where durable remission has been reported. This article outlines the role of systemic and intrathecal chemotherapy in patients with leptomeningeal metastases. Strategies for symptom management in these patients are also described.

Adult↗
PubMed2003

Combined-modality treatment of leptomeningeal gliomatosis.

OBJECTIVE: Leptomeningeal gliomatosis (LG) is a clinically uncommon metastatic complication of high-grade gliomas (HGGs), for which there is no consensus regarding treatment. The goal of this study was to determine the toxicity and response rate of combined-modality therapy for the treatment of patients with HGGs and LG. METHODS: Eighteen patients (10 men and 8 women), ranging in age from 28 to 70 years (median, 38 yr), with clinically, neuroradiologically, and cytologically documented LG received intraventricular chemotherapy. Tumor histological types included anaplastic astrocytoma (10 patients) and glioblastoma multiforme (8 patients). Concurrent radiotherapy (11 patients) or systemic chemotherapy (13 patients) was administered as clinically indicated. Methotrexate was administered initially, and treatment was continued for patients in stable or improved condition. For patients who experienced progression, cytosine arabinoside was administered as second-line therapy, followed by N,N',N"-triethylenethiophosphoramide as third-line therapy. Patients underwent bimonthly evaluations with cerebrospinal fluid cytological assessments and neurological examinations. RESULTS: Four to 13 cycles (median, 5 cycles) of intraventricular chemotherapy were administered. Toxicity included aseptic meningitis (12 patients), radiation-induced enteritis (2 patients), and myelosuppression of Grade II or less (4 patients). No patient required hospitalization or transfusions, and no treatment-related deaths occurred. Partial responses were observed for 6 patients, and 12 patients demonstrated progressive disease. The median duration of response was 3 months (range, 2-4 mo). Survival times after the initiation of intraventricular chemotherapy ranged from 2 to 8 months (median, 3.5 mo). The cause of death was progressive LG (14 patients), combined LG and HGG (3 patients), and HGG (1 patient). CONCLUSION: For this small cohort of patients, combined-modality therapy had modest toxicity but minimal palliative efficacy. For the majority of patients with LG, supportive care should be considered.

Adult↗
PubMed2002

Salvage chemotherapy for recurrent spinal cord ependymona.

BACKGROUND: Ependymomas are reported to constitute 4% of all primary central nervous system (CNS) malignancies in adults, 30% of which occur in the spinal cord. A prospective Phase II study to determine toxicity and response to chronic oral etoposide in patients with recurrent low-grade intramedullary spinal cord ependymoma (SCE) was conducted. METHODS: Ten patients (6 males and 4 females with a median age of 30 years) with recurrent SCE were treated with oral etoposide (50mg/m(2)/day given daily for 21 days followed by a 14-day break and then repeated constituted a cycle of therapy). All patients had failed surgery and radiotherapy and four patients had failed one prior chemotherapy. Blood counts were obtained weekly, and neurologic examination and a chemistry panel were performed monthly. Contrast-enhanced magnetic resonance imaging of the spine was performed every 8 weeks after a cycle of etoposide and before the next cycle of chemotherapy was initiated. RESULTS: Treatment-related complications included alopecia in 9 patients, nonbloody diarrhea in 6 patients, a baseline weight loss of > 10% in 5 patients, Grade (according to the National Cancer Institute Common Toxicity Scale) 3-4 neutropenia in 3 patients, Grade 3-4 thrombocytopenia in 3 patients, and Grade 3-4 anemia in 2 patients. There were no treatment-related deaths reported. After 1 cycle of etoposide, 3 patients (30%) demonstrated progressive disease, 2 patients (20%) achieved a partial response, and 5 patients (50%) maintained stable disease. The overall median response or stable disease duration (disease-free progression) was 15 months (range, 2.5-45+ months). The overall median survival was 17.5 months (range, 3-45+ months). CONCLUSIONS: Chronic oral etoposide appears to be well tolerated, has modest toxicity, and had apparent activity in the small cohort of adults in the current study with surgically and medically refractory, recurrent, intradural intramedullary SCE.

Administration, Oral↗
PubMed2002

Treatment of intracranial metastatic esthesioneuroblastoma.

BACKGROUND: Esthesioneuroblastoma (ENB) is an uncommon tumor that may metastasize to the central nervous system (CNS). To the authors' knowledge there is no current consensus regarding treatment. The current study was conducted to determine the toxicity and response rate of combined modality therapy in the treatment of patients with ENB metastatic to the brain. METHODS: Six patients (2 men and 4 women) ranging in age from 47-61 years (median age, 53.5 years) with ENB had clinical and neuroradiographic evidence of CNS metastases (brain parenchyma in 6 patients and leptomeningeal metastases in 3 patients). CNS-directed therapy included radiotherapy (to the brain in three patients and to the spine in two patients) and chemotherapy (systemic in six patients and regional in three patients). Systemic chemotherapy was comprised of carboplatin, lomustine, and vincristine administered every 2 months. Patients were evaluated by neuroradiographic and neurologic examination every other month. RESULTS: Between 1-6 cycles of systemic chemotherapy were administered (median, 4.5 cycles). and 6-19 cycles of regional chemotherapy were administered (median, 17 cycles). Toxicity included aseptic meningitis (three patients), radiation enteritis (one patient), and > or = Grade 3 (according to the National Cancer Institute Common toxicity Criteria) myelosuppression (four patients). Two patients required hospitalization for neutropenic fever and two patients required a transfusion (platelets in two patients and red blood cells in one patient). No treatment-related deaths were reported. A partial response was achieved in four patients, and two patients demonstrated progressive disease. The median duration of response was 9 months (range, 2-12 months). Overall survival ranged from 3-13 months (median, 10.5 months). The cause of death was progressive parenchymal brain disease in three patients, systemic disease in two patients, and leptomeningeal disease in one patient. CONCLUSIONS: In the small cohort of patients in the current study, combined modality therapy was found to have modest toxicity and palliative efficacy.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

A phase II trial of intra-cerebrospinal fluid alpha interferon in the treatment of neoplastic meningitis.

BACKGROUND: Neoplastic meningitis (NM), a metastatic complication of both primary central nervous system and systemic cancer, occurs in 1-5% of patients with known cancer. Currently available treatment options are limited and provide only modest benefit. The current study was performed to determine the toxicity and response rate of intra-cerebrospinal fluid (CSF) alpha interferon (alpha-IFN) in the treatment of patients with NM. METHODS: Twenty two patients (median age, 56 years) with clinical and cytologically documented NM received intra-CSF alpha-IFN. Tumor histologies included: lung (five patients); brain (five patients); non-Hodgkin lymphoma (three patients); breast (three patients); melanoma (two patients); chronic myelogenous leukemia (two patients); colon (one patient); and prostate (one patient). Concurrent involved-field radiotherapy (12 out of 22 patients) or systemic chemotherapy (11 out of 22) was administered based on clinical indications. -alpha-IFN was administered at a fixed dose (1 x 10(6) IU every other day given three times per week for four weeks by induction). Patients were evaluated by CSF cytology and neurologic examination at the conclusion of induction therapy. Responding patients continued to receive alpha-IFN with monthly evaluations. RESULTS: Ten out of 22 patients (45%) treated with alpha-IFN had a cytologic response and either stable or improved neurologic status at the conclusion of induction. Duration of response ranged from 8 to 40 weeks (median, 16 weeks). Toxicity was manifested as transient chemical arachnoiditis (16 out of 22 patients; 60% of all treatment cycles) and chronic fatigue (20 out of 22 patients). No treatment-related hospitalizations or deaths were seen. CONCLUSIONS: alpha-IFN has modest activity against NM. However, it is associated with considerable toxicity at the dose and schedule used in the current study and, as a result, may prove difficult to administer.

Adult↗
PubMed2002

Neoplastic meningitis.

Neoplastic meningitis (NM) is a common problem in neuro-oncology, occurring in approximately 5% of all patients with cancer. Notwithstanding frequent focal signs and symptoms, NM is a disease that affects the entire neuraxis; therefore, staging and treatment need to encompass all cerebrospinal fluid (CSF) compartments. Central nervous system (CNS) staging of NM includes contrast-enhanced cranial computerized tomography or magnetic resonance imaging, contrast-enhanced spine magnetic resonance imaging or computerized tomographic myelography, and radionuclide CSF flow study. Treatment of NM involves involved-field radiotherapy of bulky or symptomatic disease sites and intra-CSF drug therapy. The inclusion of concomitant systemic therapy may benefit patients with NM and may obviate the need for intra-CSF chemotherapy. At present, intra-CSF drug therapy is confined to three chemotherapeutic agents (ie, methotrexate, cytosine arabinoside, and thio-triethylene thiophosphoramide) administered by a variety of schedules either by intralumbar or intraventricular drug delivery. Although treatment of NM is palliative with an expected median patient survival of 2 to 6 months, it often affords stabilization and protection from further neurologic deterioration in patients with NM.

Central Nervous System Neoplasms↗
PubMed2002

Salvage chemotherapy with CPT-11 for recurrent glioblastoma multiforme.

BACKGROUND: A prospective Phase II study of CPT-11 in adult patients with recurrent supratentorial glioblastoma multiforme (GBM). METHODS: Forty patients (25 men, 15 women) ages 32-71 years (median 59), with recurrent GBM were treated. All patients had previously been treated with surgery and involved field radiotherapy (median dose 60 Gy; range 59-60). Additionally, all patients were treated with adjuvant chemotherapy (BCNU in 20, PCV in 18, Procarbazine in 2). Twenty-five patients (62%) were on anticonvulsants (phenytoin in 15, carbamazepine in 10) and 26 patients (65%) were on dexamethasone. Recurrent disease was defined by neuroradiographic disease progression (>25% increase in tumor dimensions) using gadolinium-enhanced MR imaging. The starting dose of CPT-11 was 400 mg/m2 followed in three weeks by 500 mg/m2, operationally defined as one cycle. At week 6, all patients were evaluated with MRI and neurological examination. RESULTS: All patients were evaluable. Two doses (one cycle) of CPT-11 were administered to all patients. CPT-11-related toxicity included: diarrhea (16 patients, 40%); thrombocytopenia (9 patients, 23%); and neutropenia (6 patients, 15%). No patient required transfusion nor was treatment for neutropenic fever required. No treatment-related deaths were observed. All patients demonstrated progressive disease following one cycle of CPT-11. CONCLUSIONS: The lack of response to CPT-11 in this patient group with recurrent GBM suggests either CPT-11 has minimal activity or CPT-11 doses/schedule utilized in this study were sub-optimal. The latter is supported by the modest toxicity seen in this study and the previously documented enhanced clearance of CPT-11 in patients on anticonvulsants and dexamethasone.

Adult↗
PubMed2002

Salvage chemotherapy with CPT-11 for recurrent oligodendrogliomas.

OBJECTIVE: A prospective Phase I study designed to establish the maximum tolerated dose and secondarily evaluate response rate to CPT-11 in patients with recurrent oligodendrogliomas (oligos) on anticonvulsant drugs (AEDs). BACKGROUND: Oligos, which constitute 1-2% for all adult brain tumors, are commonly treated with procarbazine, CCNU and vincristine (PCV) chemotherapy. How to treat oligos that have failed PCV, surgery and radiotherapy is more problematic. DESIGN/METHODS: Fifteen patients (age range 24-55 years; gender 10 males; 5 females) with recurrent oligos and on AEDs were treated prospectively with CPT-11. Four cohorts of patients defined by CPT-11 dose were treated. Three patients were treated with 400 mg/m2 every 3 weeks, 3 patients 500 mg/m2, 6 patients 600 mg/m2 and 3 patients 700 mg/m2. Neuroradiographic evaluation was performed after every other dose of CPT-11. In patients with stable or responding disease, two further doses of CPT-11 were administered. Alternative or supportive care was offered to patients with disease progression. RESULTS: Toxicity included neutropenia (3 patients; 1 each with Grade III and Grade IV toxicity); thrombocytopenia (2 patients; 1 with Grade IV toxicity); abdominal pain with or without diarrhea (5 patients; 1 with Grade III toxicity) nausea/vomiting (4 patients). No patient required hospitalization nor did a treatment-related death occur. One patient required a platelet transfusion. Toxicity was a function of CPT-11 dose and the maximum tolerated dose was 600 mg/m2. Cycles (2-12) of CPT-11 were administered (median 4). Response was as follows: partial response (2 patients); stable disease (5 patients); and progressive disease (8 patients). Duration of response ranged from 1.5 to 9 months with a median of 3. In patients with either stable disease or a partial response, response duration was 4.5-9 months (median 6 months). Progression-free survival at 6 months was 33% and 0% at 12 months. Overall survival following initiation of CPT-11 ranged from 2 to 12 months (median 3 months). In patients with either stable or responding disease, median survival was 7 months (range 6-12 months). CONCLUSION: In this small cohort of patients with recurrent low-grade oligos having been treated previously with PCV and on cytochrome P450 enzyme inducing AEDs, CPT-11 has modest palliative efficacy and acceptable toxicity. A dose of 600 mg/m2 every 3 weeks of CPT-11 in patients on AEDs is suggested based on toxicity analysis.

Adult↗