Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0017638 (glioma)
 30,880 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-four patients with recurrent malignant glioma were treated with intravenous BCNU (80 mg/m2/day X 3 days) alternating with AZQ (8 mg/m2/day X 5 days) every 6-8 weeks. Twenty patients received two or more courses of chemotherapy, ten anaplastic astrocytomas (AA), eight glioblastomas (GBM), and two malignant oligodendrogliomas (Oligo). All had prior surgery and irradiation; one had prior chemotherapy. Median age was 37.5 years. The median Zubrod performance status (PS) was 1. Three patients (15%) achieved response status, and 7 (35%) had stable disease with median times to tumor progression (MTP) of 56 wks and 35 wks. MTP for patients with progression was 11 weeks. No GBM was responsive to chemotherapy and none of the ten patients with stable or responsive disease were older than fifty years. Dose limiting toxicity was consisted of thrombocytopenia and leukopenia. Young patients with recurrent AA and good PS appear more likely to respond to alternating BCNU/AZQ chemotherapy. The overall response rate (response plus stable) of 50% was comparable to that of BCNU alone and the hematologic toxicity was cumulative.
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PMID:Intravenous BCNU and AZQ in patients with recurrent malignant gliomas. 279 18

Sixty consecutive evaluable children with recurrent primary tumors of the central nervous system were treated with a regimen of vincristine, nitrogen mustard, procarbazine, and prednisone over a 12-year period. Tumor types included medulloblastoma (19), brain-stem glioma (16), astrocytoma (13), and a miscellaneous glioma (12). Responses and sustained survivals were achieved. Responses were highly dependent on tumor type. Disease progression was halted in 73% of the children with medulloblastoma, and three have survived in complete remission for more than 10 years from the start of therapy with vincristine, nitrogen mustard, procarbazine, and prednisone. Two of four patients with anaplastic glioma, are long-term survivors. In contrast, less than one third of children with brain-stem gliomas responded. Toxicity consisted mainly of neutropenia, thrombocytopenia, infections, and rarely a procarbazine rash.
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PMID:Salvage chemotherapy for recurrent primary brain tumors in children. 341 10

Carboplatin, a cisplatin analogue, was administered as an intravenous (IV) one-hour infusion in a 4-consecutive weekly dose schedule to 44 patients with recurrent childhood brain tumors. Twenty-four patients were registered on our phase I, and 20 on our phase II studies. The maximum tolerable dose derived from our phase I study was 210 mg/m2/wk in patients with solid tumors, and the recommended dose for subsequent pediatric phase II studies was 175 mg/m2/wk. This dose was administered to 14 patients in the phase I and all 20 patients in the phase II study. Nine of 36 (25%) evaluable patients in the combined studies experienced objective responses for a median duration of 10+ months. Seven of nine responders had received prior cisplatin. Disease-specific response rates were as follows: medulloblastoma, six of 14 (43%) with three complete (CR) and three partial responses (PR); pineoblastoma, one of one (PR); germinoma, one of two (CR); and brainstem glioma, one of eight (13%) (PR). Carboplatin had mild emetic effects but no significant auditory or renal toxicity. Thrombocytopenia (less than 49,000) was encountered in nine of 28 (32%) evaluable trials at a dose of 175 mg/m2/wk. Because of its low potential for auditory, renal, and emetic toxicity, ease of administration, and high disease-specific activity, carboplatin deserves further study in multiagent phase II and III trials, especially in chemotherapy-sensitive diseases such as medulloblastoma.
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PMID:Carboplatin and recurrent childhood brain tumors. 354 20

PCNU, the latest nitrosourea analogue to be subjected to clinical trials, held promise as a superior chemotherapy agent for brain tumors because of more favorable biochemical and cytotoxic characteristics in laboratory studies. Thirty-nine children with a variety of recurrent primary CNS tumors, all of whom had evaluable disease, participated in a phase II PCNU trial. Their mean age was 9.7 (3-20) years. PCNU was administered as a 2 hour intravenous infusion in one of 2 dose schedules at 6-7 week intervals; 100-125 mg/m2 for minimally treated patients and 70-90 mg/m2 for heavily treated patients. Response was assessed after 2 courses of chemotherapy after attempting to taper the steroid dose. The overall objective response rate was 18% (7/39) for a mean of 5.9 months (2+ -12). Only partial responses were observed. Disease-specific responses rates were: brainstem glioma--18% (3/17); cerebral glioma--27% (3/12); ependymoma--1/1; and primitive neuroectodermal tumors--(0/9) including 5 medulloblastomas, 2 pineoblastomas and 3 cerebral primitive neuroectodermal tumors. Toxicity was primarily hematologic and clinically significant thrombocytopenia (less than 50,000 mm3) was encountered in 30/38 (79%) patient trials. Modest activity of PCNU in recurrent childhood gliomas is confirmed. Our response rates, using objective CT criteria, are somewhat lower than those reported for BCNU and CCNU. Because of comparable hematologic toxicity and efficacy, intravenous PCNU does not appear to offer a clinical advantage to existing nitrosoureas for children with recurrent brain tumors using a 2 hour intravenous infusion schedule.
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PMID:PCNU and recurrent childhood brain tumors. 368 86

Diaziquone, a new alkylating agent which crosses the blood brain barrier, has shown a 20% response rate in phase II studies in heavily pretreated patients. We have treated 23 patients at our institution as part of a multicentric phase II European trial of diaziquone. All had histologically proven malignant glioma unequivocally progressing on CT scan. Prior therapy had consisted of surgical excision (13 patients), cobalt radiotherapy to CNS (13 patients), and chemotherapy with nitrosourea derivatives (11 patients). Six patients had no prior therapy. Median age was 42 years (range 22-69) and performance status was 3+ or better. They were treated with monthly courses of diaziquone 5.5 mg/m2 I.V. (10 min.) X 5 days. Dosage adjustments were made according to leucocyte and platelet nadirs. Thrombocytopenia was the dose limiting toxicity. Very mild gastrointestinal toxicity was observed. One patient developed hemolytic anemia. One complete response (clinical and CT scan), 7 partial clinical responses (3: greater than 50%, 4: 25-50%), and 1 disease stabilization (less than 25%) were documented. The longest response has now lasted over 26 months. These preliminary results show that chemotherapy with diaziquone can achieve a response rate as high as 35% in malignant glioma even in patients previously treated with a chemotherapy regimen including a nitrosourea (four of the seven objective responses were seen in such patients). Diaziquone is well tolerated and deserves further study in the management of malignant glioma.
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PMID:Phase II evaluation of diaziquone (CI-904, AZQ) in the treatment of human malignant glioma. 405 53

Extraneural metastases from malignant glioma and glioblastoma are believed to be rare. The most common sites of metastases are lung, lymph nodes, bone, and liver. We recently encountered two patients with glioblastoma multiforme who presented with pain and thrombocytopenia caused by diffuse metastasis to bone marrow. A premortem diagnosis was established in the first patient with the aid of peroxidase-antiperoxidase staining of the bone marrow biopsy specimen for glial fibrillary acidic protein, a glial-specific marker. In the second patient glial fibrillary acidic protein staining confirmed the glial nature of the primary brain tumor as well as the metastatic tumor in bone marrow. The first patient also had metastatic nodules on the pleural surface and on the fifth rib. All three metastatic foci had similar cellular morphology, suggesting selection of a population of tumor cells with extraneural metastatic potential.
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PMID:Diffuse bone marrow metastasis by glioblastoma: premortem diagnosis by peroxidase-antiperoxidase staining for glial fibrillary acidic protein. 631 36

The authors examined the growth rate of mouse 203 glioma cells in vitro and found it to be markedly inhibited after exposure to ACNU for 5 minutes at a drug concentration of 100 micrograms/ml. Rats that had undergone intracranial implantation of T1 neurogenic tumor were treated by 5 mg/kg of ACNU administered either intravenously or intra-arterially. The median survival times for the control animals and the animals undergoing intravenous or intracarotid administration of ACNU were 23, 29, and 46 days, respectively. The difference in survival time between the intravenous and intracarotid administration groups was statistically significant (p less than 0.01) when examined by the Cox-Mantel test. In a clinical trial, 17 patients with glioblastoma were treated by ACNU, eight intravenously and nine by the intra-arterial route. The drug was given in doses of 2 to 3 mg/kg at least twice before and twice after a course of postoperative radiotherapy. Intra-arterial administration was performed over a period of 5 minutes under local anesthesia. The median postoperative survival time for the patients in the intra-arterial group was 12.5 months, compared with 9.0 months for those in the intravenous group. The survival rate for the intra-arterial group was slightly higher, although statistically not significant, probably because the number of cases was small. The degree of thrombocytopenia due to ACNU tended to be less marked in the intra-arterially treated patients. The theoretical advantages of the intra-arterial administration of ACNU are discussed.
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PMID:Intra-arterial ACNU therapy for malignant brain tumors. Experimental studies and preliminary clinical results. 657 43

Within three weeks of definitive surgical intervention, 467 patients with histologically proved malignant glioma were randomized to receive one of four treatment regimens: semustine (MeCCNU), radiotherapy, carmustine (BCNU) plus radiotherapy, or semustine plus radiotherapy. We analyzed the data for the total randomized population and for the 358 patients in whom the initial protocol specifications were met (the valid study group). Observed toxicity included acceptable skin reactions secondary to radiotherapy and reversible leukopenia and thrombocytopenia due to chemotherapy. Radiotherapy used alone or in combination with a nitrosourea significantly improved survival in comparison with semustine alone. The group receiving carmustine plus radiotherapy had the best survival, but the difference in survival between the groups receiving carmustine plus radiotherapy and semustine plus radiotherapy was not statistically significant. The combination of carmustine plus radiotherapy produced a modest benefit in long-term (18-month) survival as compared with radiotherapy alone, although the difference between survival curves was not significiant at the 0.05 level. This study suggests that it is best to use radiotherapy in the post-surgical treatment of malignant glioma and to continue the search for an effective chemotherapeutic regimen to use in addition to radiotherapy.
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PMID:Randomized comparisons of radiotherapy and nitrosoureas for the treatment of malignant glioma after surgery. 700 Dec 30

Twenty-six patients with cerebral malignant glioma (7 cases of astrocytoma Grade 3, and 19 of astrocytoma Grade 4) were treated by intra-arterial and local administration of MCNU. Nineteen patients were treated in combination with local radiation in a dose of 60 Gy. Intra-arterial administration of MCNU was performed by puncture of the ipsilateral common carotid artery and injection of 25mg of MCNU in 20 ml of physiological saline. Local administration of MCNU was performed by puncture of the Ommaya reservoir placed within the cavity after tumor resection. Objective tumor regression was observed on computerized tomography (CT) scans after intra-arterial and/or local administration of MCNU combined with radiotherapy in three of seven patients who had evaluable enhanced lesions on CT after surgery. It was also observed after chemotherapy alone in one of three patients with evaluable lesions. The response rate was 42.9% among patients treated with MCNU in combination with radiotherapy, and 33.3% in patients treated with MCNU alone. In two patients, local administration of MCNU induced brain edema, which was transient and caused no neurological sequelae. One patient suffered mild thrombocytopenia after seven intra-arterial doses of MCNU, however, no myelosuppression requiring administration of gamma-GCSF or blood transfusions was observed. These findings suggest that intra-arterial and local administration of MCNU can be expected to serve as effective and non-myelosuppressive chemotherapy in patients with cerebral malignant gliomas.
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PMID:[Effect of intra-arterial and local administration of MCNU on cerebral malignant gliomas]. 775 90

Thirty-two patients with recurrent glioma who had previously received radiation therapy and chemotherapy with nitrosoureas were treated with intravenous carboplatin every 3 weeks, starting at a dose of 350 mg/m2, with a dose escalation of 25 mg/m2 every 6 weeks until a level 4 hematologic toxicity was reached. Of the 28 patients who could be evaluated for a response, 50% demonstrated a response or had stabilization of their disease after two infusions of carboplatin. Their median time to tumor progression and median duration of survival were 19 weeks and 38 weeks. Thrombocytopenia was the major toxicity and was severe in one-third of the patients. No neurologic or renal toxicities were noted. Carboplatin has demonstrated activity against recurrent gliomas in patients who have already had extensive chemotherapy. Increasing the dose of carboplatin may improve the rate of response and the duration of progression-free survival in patients with recurrent glioma.
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PMID:A phase II study of intravenous carboplatin for the treatment of recurrent gliomas. 781 6


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