Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Twenty-nine patients with recurrent malignant brain tumors were evaluated. BCNU (180 mg/m2) was administered iv on Day 1 and 5-fluorouracil (1 g/m2/day) was given by continuous infusion on Days 15--17. Courses were repeated every 6 weeks until tumor progression occurred. Before each course, a neurologic examination and radionuclide and computerized tomographic scans were performed. Response and progression were defined as improvement or deterioration, respectively, in at least two of the three tests. Nine of 29 patients (31%) responded to therapy, five of 29 (17%) showed progression, and 15 of 29 (52%) had disease stability. The estimated median time to progression was 27 weeks for all patients, 34 weeks for the response group, and 25 weeks for the stable group. Of all 29 patients, 24 (83%) had tumor progression arrested; 40% with response and 6% with stable disease were continuing therapy after 1 year. The stable disease group was larger and the duration of stability was longer than that seen in previous studies. Evaluated by time to progression, a BCNU-5-fluorouracil combination is superior to either BCNU alone or a BCNU-procarbazine combination.
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PMID:BCNU-5-fluorouracil combination therapy for recurrent malignant brain tumors. 22 Nov 13

Twenty-one patients with grade III or IV astrocytomas were assigned randomly to receive either BCNU alone or BCNU and VM-26 after surgery and radiation therapy. Patients surviving radiation therapy and receiving single-agent chemotherapy had a median survival of 14 months while those receiving combination chemotherapy had a median survival of 22 months (P greater than 0.05). None of the patients who failed BCNU-only therapy responded to VM-26. Performance status was not affected by either regimen. Computerized tomographic scanning of the brain was useful only in confirming tumor progression. Two patients died from BCNU-related interstitial pulmonary fibrosis.
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PMID:Treatment of grade III and IV astrocytomas with BCNU alone and in combination with VM-26 following surgery and radiation therapy. 23 Aug 93

During chemotherapy and regrowth of brain tumors, tumor-cell heterogeneity, and possibly tumor progression, may change as a result of both the selective forces and mutagenic effects of treatment. We have isolated and characterized drug-response variants of multicellular rat 9L brain-tumor spheroids exposed to 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Ten colonies were isolated from spheroids disaggregated immediately after treatment, and 10 colonies were isolated from treated spheroids disaggregated after 1 week in suspension culture. The sensitivity to BCNU was determined by assays of sister chromatid exchange and colony-forming efficiency in monolayer cultures of each subline after a 1-hr exposure to graded doses of BCNU. Three classes of response were found: BCNU sensitivity increased, decreased, or was comparable to that of uncloned, parent 9L cells. Resistant phenotypes were predominant (8/10) in sublines from spheroids disaggregated immediately after treatment, whereas hypersensitive phenotypes (4/8) were isolated only from spheroids disaggregated after 1 week of regrowth. Since subpopulations isolated immediately after treatment do not have the same biological characteristics as those isolated after a period of regrowth, these data suggest that tumor-cell heterogeneity may be generated by distinct processes at various times during therapy. The predominance of hypersensitive sublines obtained by the regrowth protocol may have resulted from the recovery of cells that would have died if isolated but were instead able to repair the drug-induced damage when left in contact with neighboring, possibly resistant cells. Two resistant and two hypersensitive sublines were studied further.
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PMID:Production of stable phenotypes from 9L rat brain tumor multicellular spheroids treated with 1,3-bis(2-chloroethyl)-1-nitrosourea. 139 17

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

Twenty-three patients with malignant melanoma metastatic to the central nervous system (CNS) were treated with intracarotid cisplatin-based chemotherapy. Twenty-two had failed prior cranial radiation therapy (one patient refused radiation therapy) and had progressive brain metastases documented by computerized tomography (CT). Intracarotid cisplatin 40-75 mg/m2 was administered alone (seven patients) with 1,3-bis(2-Chloroethyl)-1-nitrosourea (BCNU) (13 patients) or bleomycin (three patients). Courses were repeated monthly with CT scan. Seven patients (30%) had objective improvement in CT scans and three patients (13%) had stabilization of disease. The median time to tumor progression for responding patients was 20 weeks (range 8-34 weeks) while stable disease ranged from 9-12 weeks. In three patients the extracranial disease progressed while the brain metastases responded. Neurological and retinal toxicity were potential complications of therapy. Intracarotid cisplatin-based chemotherapy may be useful for palliation in selected patients with malignant melanoma and CNS metastases.
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PMID:Intracarotid cisplatin-based chemotherapy in patients with malignant melanoma and central nervous system (CNS) metastases. 169 2

Between March, 1983, and February, 1989, 19 infants or children with chiasmal/hypothalamic gliomas were treated with chemotherapy after either surgical or radiological diagnosis. The patients ranged in age from 15 weeks to 15.6 years (median 3.2 years) at the start of therapy. Twelve patients were treated immediately after diagnosis because of progressive symptoms, and seven received chemotherapy after either radiographic progression or clinical deterioration, including progressive visual loss or intracranial hypertension. Based on biopsy results, seven of these tumors were classified as juvenile pilocytic astrocytomas, two as astrocytomas, two as highly anaplastic astrocytomas, and one as a subependymal giant-cell astrocytoma. There was associated neurofibromatosis in four patients. The two initial patients were treated with either actinomycin D and vincristine or 5-fluorouracil, hydroxyurea, and 6-thioguanine. The remaining patients received nitrosourea-based therapy; 15 evaluable patients were treated with a five-drug regimen that included 6-thioguanine, procarbazine, dibromodulcitol, 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU), and vincristine and one received 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) and 5-fluorouracil. Fifteen of the 18 evaluable patients initially managed with chemotherapy either responded to therapy or their condition stabilized. Median time to tumor progression has not been reached at a median follow-up period of 79 weeks (range 6.6 to 303 weeks), and no tumor-related death has occurred with a median follow-up period of 79 weeks (range 18 to 322 weeks) from the initiation of therapy. The four patients who failed therapy or whose disease progressed after chemotherapy were treated satisfactorily with radiation therapy. Initial improvement or stabilization of visual function was obtained in 16 patients. Endocrine function remained stable in all patients during treatment, although three patients required pharmacological treatment for endocrinopathy that was present at diagnosis. These preliminary results suggest that nitrosourea-based cytotoxic regimens are useful for the initial treatment of children with chiasmal/hypothalamic gliomas, and allow potentially harmful radiation therapy to be deferred until progression of disease.
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PMID:Management of chiasmal and hypothalamic gliomas of infancy and childhood with chemotherapy. 190 97

Data from Northern California Oncology Group protocol 6G61, which was closed in February 1983, were reanalyzed in December 1988. The protocol called for a randomized trial that compared the effects of following 60 Gy radiation/oral hydroxyurea treatment with either carmustine (BCNU) or the combination of procarbazine, lomustine (CCNU), and vincristine (PCV) for two histologic strata: glioblastoma multiforme and other anaplastic gliomas. PCV produced longer survival and time to tumor progression than BCNU for both histologic groups, although the difference was statistically significant only for the anaplastic gliomas. With PCV treatment, time to progression and survival doubled for anaplastic glioma patients in the 50th and 25th percentiles.
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PMID:Superiority of post-radiotherapy adjuvant chemotherapy with CCNU, procarbazine, and vincristine (PCV) over BCNU for anaplastic gliomas: NCOG 6G61 final report. 215 18

Thirty patients with histologically verified malignant supratentorial gliomas were treated with a preirradiation chemotherapy protocol consisting of two courses of intracarotid (i.c.) CDDP, 90 mg/m2, followed by i.v. BCNU, 200 mg/m2. Side effects from therapy were mild and self-limiting; no irreversible retinal or neurologic toxicity could be attributed to i.c. chemotherapy. Of the 27 patients who completed the chemotherapy portion of the protocol, tumor size on postchemotherapy computed tomography (CT) was decreased by greater than 50% in 13% as compared to the postoperative CT scan; in only 4% was the CT scan unequivocally increased in size. Twenty-five (83%) patients completed the entire protocol. Median time to tumor progression and survival in patients who completed the protocol was 53 (range of 13-130+) and 61 (range of 29-130+) weeks, respectively. Twenty-four percent of patients still have not demonstrated tumor progression at intervals greater than 1 year after diagnosis as judged by clinical and radiographic criteria. Tumor recurrences were always contiguous to the original tumor bed. We conclude that preirradiation chemotherapy may be administered safely and with low morbidity. Further study to determine an optimal timing between chemotherapy and radiation therapy is warranted.
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PMID:Preirradiation chemotherapy of supratentorial malignant primary brain tumors with intracarotid cis-platinum (CDDP) and i.v. BCNU. A phase II trial. 215 17

Twelve patients aged 34 to 65 with malignant gliomas were treated with VP-16, Procarbazine, Vincristine and concurrent radiation therapy. There were 9 patients with glioblastoma multiforme and 3 with anaplastic astrocytoma. All patients had a subtotal resection or biopsy as the initial procedure. Six patients (1 anaplastic astrocytoma) have developed progressive disease. Mean time to tumor progression was 46 weeks. This combined modality treatment program was associated with reversible hematologic toxicity which was severe in 2 patients. These data compare favorably to data obtained from similar patients treated with radiation therapy and BCNU.
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PMID:VP-16, vincristine and procarbazine with radiation therapy for treatment of malignant brain tumors. 216 15

Twenty-six patients with intracerebral tumors (predominantly gliomas) were treated with intraarterial BCNU, VM-26, and cisplatin combined with the systemic administration of VM-26, methotrexate, vincristine, bleomycin, and procarbazine. Oral glycerol was given before i.v. VM-26. Twelve patients responded (46% of all patients and 63% of the fully evaluable patients). The response rate for gliomas was 50% if all patients were considered and 71% if only fully evaluable patients were considered. The response rate did not seem to be affected by glioma grade, prior chemotherapy, or pretreatment performance status. Median time to tumor progression for responders was 19 weeks. Median survival from initiation of treatment was 21 weeks for evaluable patients and 17 weeks for all patients. Median survival from initial diagnosis was 55 weeks. Myelosuppression was dose-limiting for the systemic chemotherapy. Reversible neurological toxicity was common, but tolerable. One patient developed ipsilateral blindness, and two patients developed prolonged neurological toxicity. Pulmonary toxicity was also seen. Vertebral artery infusions proved feasible, although difficult and more toxic than carotid infusions. Overall, this regimen was not more active than the intraarterial combination of BCNU, VM-26, and cisplatin without the systemic chemotherapy. Further studies of more intensive intracarotid therapy combined with different systemic drugs are being initiated.
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PMID:Combined intraarterial and systemic chemotherapy for intracerebral tumors. 244 73


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