Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023380 (lethargy)
 5,697 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acivicin (AT-125) is a glutamine antagonist with dose-limiting, schedule-dependent CNS toxicity and predictable CSF penetration after intravenous administration. Because of these properties, a trial in CNS malignancies was initiated. Thirty-two patients with recurrent or residual malignant astrocytomas were treated with AT-125. The majority of patients had glioblastoma multiforme (24) and had received prior nitrosoureas (21). The median age was 50 years, and Southwest Oncology Group (SWOG) performance status was 2. The major determinant of response was based upon radiologic criteria using computed tomographic (CT) scanning and/or magnetic resonance imaging (MRI) scans. The tumor mass was measured in two perpendicular planes, which yielded the largest cross-sectional area. Standard solid tumor criteria for response were used. All responding patients also had a stable or tapered dose of corticosteroids with stable or improved performance status and neurologic examination. There were four objective responses (12%): one complete remission (3 1/2+ years) and three partial remissions (57, 86, and 322 days). Two patients had improvement in disease that did not meet requirements for a partial remission. Toxicity was mild and primarily consisted of nausea, vomiting, and lethargy. Two patients were removed from study due to neurotoxicity (depression and hallucinations). The strict response criteria used in this trial were not those that have been used in testing other active agents such as carmustine (BCNU). We conclude that AT-125 has objective antitumor activity in malignant astrocytomas and warrants further study.
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PMID:Objective antitumor activity of acivicin in patients with recurrent CNS malignancies: a Southwest Oncology Group trial. 164 69

A 41 year old male presented with headache, lethargy, and ataxia and found to have a left temporal lobe mass and a leukoerythroblastic peripheral blood smear. The latter prompted an iliac crest bone marrow biopsy on which a diagnosis of metastatic glioma was made and verified by immunohistologic characterization. The patient was treated with cranial irradiation and simultaneous systemic BCNU (bis-dichloroethylnitrosurea) with complete response. This case with diffuse bone marrow involvement demonstrates that a glioblastoma is capable of extracranial metastases without previous intervention. From a review of reported cases of gliomas of extraneural metastasis, it is concluded that untreated gliomas are capable of vascular spread although less frequently than previously manipulated tumors.
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PMID:Intracranial astrocytoma with diffuse bone marrow metastasis: a case report and review of the literature. 329 52

Intracarotid BCNU (100 mg/m2) and cisplatin (60 mg/m2) were administered to 36 patients with malignant brain tumors recurrent or progressive after cranial irradiation. Courses of therapy were repeated at 4-6 week intervals. Of 23 evaluable patients with recurrent glioma, 9 (39%) had tumor regression by CT scan and 3 had stable disease. The median time to tumor progression for responding patients was 37 weeks. For all patients with primary tumors it was 14 weeks. Six of 9 patients with no prior chemotherapy had a response and 1 had stable disease. Of 14 patients who had received prior chemotherapy, 3 had a response and 2 had stable disease. Survival ranged from 9 weeks to 95+ weeks (median 34 weeks) from start of therapy. Six of 23 patients with primary tumors are alive 1 year or more following therapy. Four of 11 patients with brain metastases had a response and 2 had stable disease. Major neurologic toxicity of intracarotid BCNU and cisplatin appeared cumulative and consisted of reversible hemiparesis in 3% of 118 courses, TIA in 1%, expressive aphasia in 9%, lethargy in 3%, seizures in 12%, and reversible confusion in 1%. Retinal toxicity consisted of mild blurring of vision in 4 patients and ipsilateral blindness in 5 patients. Three of 22 patients who had received supraophthalmic infusion later developed evidence of leukoencephalopathy. Intracarotid BCNU and cisplatin appears to have modest increase in activity over intracarotid cisplatin alone (Cancer 54:794, 1984), however, neurologic and retinal toxicity may also be increased.
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PMID:Phase II trial of intracarotid BCNU and cisplatin in primary malignant brain tumors. 370 37

Twenty-six patients affected by acute myeloid leukemia (AML) who relapsed after autologous stem cell transplantation (ASCT) were treated with the FLAG regimen (fludarabine, cytarabine, and G-CSF). Their median age was 39 years (range 14-59). The median interval from achievement of CR to ASCT was 4 months (2-8). The conditioning regimen was BAVC (BCNU, amsacrine, VP-16, cytarabine) in eight patients, BuCy (busulfan, cyclophosphamide) in 13, and TBI-Cy (total body irradiation, cyclophosphamide) in five. Relapse occurred after a median of 7 months (2-18). ASCT had been performed in CR1 for 23 patients and in CR2 for three. Nineteen patients had been given bone marrow, seven peripheral blood stem cells collected following consolidation plus G-CSF. Overall, CR was obtained by 13 patients (50%), all remitters requiring a single course. The median time for hematological recovery of neutrophils >500/microl and platelets >20,000/microl was 24 and 30 days, respectively. The median duration of G-CSF administration was 25 days, while the median hospitalization was 31 days. There were four deaths in induction (15%), while nine patients (35%) were resistant. After achieving CR, two patients received allogeneic BMT, five a second ASCT, and four were consolidated with HD-ARA-C. Only two patients were judged unable to receive any further therapy. There were 14 documented infections, while nine patients experienced fever of unknown origin. WHO >2 nonhematological toxicity consisted of stomatitis (50%), hepatic dysfunction (11%), diarrhea (11%), and lethargy (4%). Median overall survival and disease-free survival were 6 and 13 months, respectively. Six patients are in CCR at present. We conclude that FLAG is effective in patients with AML who are relapsing after ASCT. The toxicity is acceptable, enabling most patients to receive further treatment, including second transplantation procedures.
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PMID:Fludarabine, cytarabine, and G-CSF (FLAG) for the treatment of acute myeloid leukemia relapsing after autologous stem cell transplantation. 1046 Mar 53