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)

The aim of this study was to verify the tolerability and efficacy of therapeutic chemotherapy protocols, employing different combinations of cisplatin, carboplatin, etoposide and carmustine in primary glioblastoma patients. The purpose was focused on 2 end points: the response index to treatment, the TTP (tumor progression) and the ST (survival time). Eighty-four out of a group of 99 consecutive glioblastoma patients, entered this study. Patients were divided into 4 disparate treatment groups: (A) BCNU alone; (B) CDDP + VP-16; (C) CBDCA + BCNU; (D) CBDCA + BCNU + VP-16. The effectiveness and the TTP of the protocols differed, but differences were not statistically significant. Data concerning platinum treatment compare favorably with the best literature results. At 18 months more than half the carboplatin-treated patients are alive. Moreover these patients had a significantly longer ST than those treated with BCNU. We conclude that platinum-based chemotherapy has a beneficial effect on glial tumors.
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PMID:Carboplatin combined with carmustine and etoposide in the treatment of glioblastoma. 148 54

Thirty patients with recurrent malignant glioma were treated with intravenous (IV) carboplatin (CBDCA) every 4 weeks at a starting dose of 400 mg/m2 escalating to 450 mg/m2. All patients had documented recurrent tumor after prior radiotherapy but had not received prior chemotherapy. Of 29 assessable patients, four (14%) responded to the treatment for 44, 51+, 72, and 91 weeks; 10 (34%) achieved stable disease (S); while 15 (52%) had progressive disease (P). The total response (responses plus S) rate was 48%, with a median time to progression (MTP) of 26 weeks in these patients; the MTP for all 29 patients was 11 weeks. The toxic effects were mainly hematologic, with thrombocytopenia and granulocytopenia being mild at 400 mg/m2 and 450 mg/m2 doses. NO neurotoxicity or renal toxicity was encountered. These results suggest that CBCDA given at 400 mg/m2 or 450 mg/m2 every 4 weeks is marginally active in patients with recurrent malignant gliomas. Since hematologic toxicity is mild, a higher dose could possibly be given, and may increase the response rate.
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PMID:Intravenous carboplatin for recurrent malignant glioma: a phase II study. 184 86

Carboplatin has lower nephro- and neurotoxicities and better penetration into brain tissue than cisplatin. If carboplatin has comparable cytotoxicity against glioma cells, it might have a therapeutic advantage in the treatment of malignant gliomas. Using an assay of colony-forming efficiency, we compared the cytotoxicity of these two drugs in human glioma cell lines SF-126, SF-188, U87-MG, and U251-MG. The experiments were designed so that the product of in vitro drug concentration (C) and time (T) would encompass the same range of values as the C x T of the ultrafilterable platinum plasma fraction as determined by pharmacokinetic studies in man. The in vitro stability of the drugs was evaluated by measuring the cytotoxicity of aged drugs with a microculture tetrazolium assay. Cisplatin and carboplatin were both stable during the 2-h treatment. The cytotoxic activities of these drugs at clinically achievable levels of drug exposure were of the same order of magnitude. These results, in conjunction with the lower nephro- and neurotoxicities of carboplatin, the higher platinum levels in brain tissue after treatment with carboplatin, and the encouraging results of carboplatin in the clinical treatment of brain tumors that have been demonstrated in other studies, suggest that carboplatin might be preferable to cisplatin in the treatment of patients with malignant glioma.
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PMID:Comparison of the cytotoxic activities of cisplatin and carboplatin against glioma cell lines at pharmacologically relevant drug exposures. 191 43

Carboplatin is one of a series of cisplatin analogs now undergoing clinical investigation. Phase I and II trials in adults demonstrate activity in a number of human cancers and less toxicity than might be expected with the parent compound. This phase I trial was undertaken to establish the maximum tolerated dose and the recommended phase II dose in children treated by a 1-hour iv infusion every 4 weeks. Twenty-nine patients with recurrent or progressive tumor were entered in this study at the Children's Hospital of Los Angeles and Children's Memorial Hospital in Chicago between April 12, 1983, and November 27, 1984. Beginning with a dose of 350 mg/m2 (about 80% of the adult phase II dose), we escalated the dose in groups of patients to 670 mg/m2; dose-limiting myelosuppression was encountered at this dose. Fifty-seven infusions are at least partially evaluable for toxicity. Asymptomatic hypomagnesemia, hypocalcemia, and ototoxicity were observed infrequently, and nausea and vomiting were mild. One patient with a mixed glioma of the posterior fossa achieved a good partial response lasting 9 months. Stable disease for greater than or equal to 6 months was observed in three patients: one each with ependymoma, brain stem glioma, and spinal cord astrocytoma. The recommended pediatric phase II dose is 560 mg/m2 given as a 1-hour iv infusion every 4 weeks.
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PMID:Pediatric phase I trial of carboplatin: a Childrens Cancer Study Group report. 331 95

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

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

To assess the interaction of carboplatin and hyperthermia in vitro, the thermochemosensitivities of three glioma cell lines, C6 rat glioma cell line, human glioma cell lines T98G and KMG4, were examined by 3-(4,5-dimethylthiazol-2-yl) -2,5 diphenyltetrazolium bromide (MTT) assay. The cell survival of each cell line decreased according to increasing CBDCA concentration and temperature. With a certain CBDCA concentration, the cell survival at following temperature was significantly decreased from that at 37 degrees: 43 degrees C and 44 degrees C for C6 cells (2.5 micrograms/ml); 41 degrees C, 42 degrees C, 43 degrees C and 44 degrees C for C6 cells (128 micrograms/ml); 42 degrees C, 43 degrees C and 44 degrees C for KMG4 cells (8 micrograms/ml) (CBDCA concentration within parentheses). It is generally considered that the highest tolerable temperature of normal brain is 42 degrees C for 60 minutes, while under 43 degrees C, there is a possibility that a sufficient tumoricidal effect might not be obtained. This study revealed enhanced cytotoxicity of CBDCA with hyperthermia at the temperature lower than 42 degrees C and suggests the possibility to gain increased tumoricidal effect without injuring normal brain by hyperthermia at the normal-tissue-tolerant temperature with systemic administration of relatively lower dose of CBDCA.
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PMID:[Synergistic effect of carboplatin and hyperthermia in rat and human glioma cell lines]. 781 71

We measured the concentrations of MCNU and CBDCA in the serum, brain tumor and normal brain tissue. Six patients with malignant glioma were treated with intravenous chemotherapy using 80mg/m2 MCNU and 300mg/m2 CBDCA during surgery. After drug administration, specimens of serum, tumor and normal brain tissue were collected every 30 min and then the drug concentration in each sample was measured. The highest MCNU levels in all samples were obtained immediately after administration which followed by gradual decrease. On the contrary, the mean CBDCA levels in the tumor and normal tissue remained almost at a constant level, although serum CBDCA level declined rapidly as MCNU. As expected, MCNU seemed to have advantages in the treatment of brain tumors as it distributed with higher concentration in the tumor tissue than in the serum and normal brain tissue. On the contrary, CBDCA in the tumor tissue did not exceed the concentration in the serum. Nevertheless, it remained longer in the tumor tissue with a constant level, suggesting that CBDCA can achieve an effective area under the concentration versus time curve (AUC) in the brain tumor tissue to kill tumor cells.
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PMID:[Clinical pharmacokinetics of carboplatin and MCNU in malignant brain tumor and normal brain tissues]. 803 Nov 57

Optic pathway tumors are common in children with neurofibromatosis-1 (NF-1). The optimal management of these tumors is unknown, particularly when the optic chiasm and other brain structures are involved. We report the dramatic response to carboplatin in a 10-year-old girl with NF-1 and a progressive optic pathway tumor. Tumor shrinkage was accompanied by striking improvement in visual fields, return of color discrimination, and marked improvement in visual acuity. No significant toxicity was observed. One year following completion of chemotherapy the glioma remains as small or smaller than it was at the conclusion of therapy, and there has been no deterioration of vision. Carboplatin is a promising agent for the treatment of optic pathway tumors in children with NF-1.
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PMID:Carboplatin-induced regression of an optic pathway tumor in a child with neurofibromatosis. 841 4

Between April, 1992 and December, 1995, forty consecutive patients with a cerebral malignant glioma (WHO Grade III and IV) were enrolled in a trial consisting in surgery and post-operative administration of radiotherapy (4500-6000 cGy), carboplatin (CBDCA; dose of 450-600 mg/m2), and oral tamoxifen (TAM; at doses of 40, 80 or 120 mg/day). Two patients of the TAM group died in the postoperative period from a pulmonary embolism and myocardial infarction, respectively. The patients (all dosages combined) had a median survival time of 13 months from the time of diagnosis. The 12-month and 24-month survival rates were 52% and 32%, respectively. The median relapse-free survival time was 7 months. Patients treated with higher doses of TAM (80-120 mg/day) demonstrated a longer median survival rate (13 months both) and a longer 12-month survival result (58% and 76%, respectively). Patients who assumed TAM for a period longer than 3 months (group +3) have a higher median survival rate (16 months) and better 12-month and 24-month results (62% and 40%, respectively). Moreover, the median relapse-free survival time was 10 months (versus 6 months in group -3; p = 0.0038). However, it is not possible to exclude that patients of group +3 had a slower growing or a stable tumor and were well enough to assume TAM for a longer period. The results observed in the TAM-group have been compared with those of 40 matched controls treated with surgery, radiotherapy and CBDCA. These patients had a median survival time of 9 months (p = 0.04) and the 12-month and 24-month survival rates were 30% and 0%, respectively. The median relapse-free survival time was 4 months (p = 0.0014). These data suggest a potential role for combinational TAM-CBDCA therapy in the post-operative treatment of cerebral malignant gliomas; further clinical phase III trials, especially those with higher dosages of TAM are warranted.
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PMID:Tamoxifen and carboplatin combinational treatment of high-grade gliomas. Results of a clinical trial on newly diagnosed patients. 954 58


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