Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We evaluated the responses of 39 children with cancer who, after failure to respond to conventional chemotherapeutic agents, received either or both of two epipodophyllotoxins: 4'-demethylepipodophyllotoxin 9-(4,6-o-2-thenylidene-beta-D-glucopyranoside) (NSC-122819) and 4'-demethylepipodophyllotoxin 9-(4,6-o-ethylidene-beta-D-glucopyranoside) (NSC-141540). Seventeen patients has acute lymphocytic leukemia (ALL). 12 had acute nonlymphocytic leukemia (ANLL), and ten had solid tumors. Initially, the patients in each disease category were randomized to receive 50 mg/m2/dose of NSC-122819 intravenously (iv) twice weekly or 75 mg/m2/dose iv of NSC-141540 twice weekly for 4 weeks. Drug dosages and schedules of administration were adjusted during the course of the study. Although objective responses were not detected in the heterogeneous group of solid tumor patients, definite clinical responses were obtained in nine of the 29 patients with acute leukemia. The responses to the two epipodophyllotoxins were noted in patients with ALL as well as in patients with ANLL. Toxic side-effects included nausea, vomiting, diarrhea, fever, alopecia, leukopenia, and thrombocytopenia. These results, the first reported with both NSC-122819 and NSC-141540 in childhood cancer, indicate that the epipodophyllotoxins are well tolerated and may be effective against acute leukemia.
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PMID:4'-demethylepipodophyllotoxin 9-(4,6-o-2-thenylidene-beta-D-glucopyranoside) (NSC-122819; VM-26) and 4'-demethylepipodophyllotoxin 9-(4.6-0-ethylidene-beta-D-glucopyranoside) (NSC-141540; VP-16-213) in childhood cancer: preliminary observations. 110 Feb 25

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 phase I trial of fazarabine (ara-AC, 1-beta-D-arabinofuranosyl-5-azacytosine, NSC 281272) administered as a 24-h continuous infusion was performed in 24 adults with solid tumor malignancies. The majority of patients had received prior marrow-suppressive therapy. Level 7 (54.5 mg/m2/h for 24 h) was the maximum tolerated dose since during 6 evaluable first courses, 2 episodes of grade 4 granulocytopenia and 3 episodes of grade 3 occurred. Moderate thrombocytopenia also occurred at level 7 with 3 episodes of grade 1 and 1 episode of grade 4 thrombocytopenia during 6 first course treatments. Minimal myelosuppression, principally leukopenia, was seen prior to level 7. The nadir WBC through 47 courses had a linear relationship with plasma steady-state concentrations of ara-AC. The only other toxicity noted was moderate nausea/vomiting, which did not appear to be dose related. Plasma steady-state concentrations of ara-AC were reached in all patients within 4-6 h and ranged from 1.1 microM (11 mg/m2/h for 24 h) to 7.5 microM (54.5 mg/m2/h for 24 h). The mean total body clearance of ara-AC for 47 courses, levels 1-7, was 592 +/- 147 (SD) ml/min/m2 which is similar to prior pharmacokinetic data from the 24-h and 72-h infusion trials of the Pediatric and Medicine Branches, respectively. There were no objective disease responses during the trial. The recommended adult phase II dose for a 24-h infusion of ara-AC is 45-50 mg/m2/h.
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PMID:Phase I clinical trial of fazarabine as a twenty-four-hour continuous infusion. 170 65

Taxol, a novel antimicrotubule agent that enhances tubulin polymerization and microtubule stability, was administered to adults with refractory leukemias as a 24-h i.v. infusion in a Phase I study. The primary objectives were to determine the maximum tolerated dose of taxol administered on this schedule to patients with acute leukemias and describe the nonhematological toxicities which became dose limiting. The starting dose, 200 mg/m2, was based on the maximum tolerated dose in solid tumor trials, in which myelosuppression precluded dose escalation. Seventeen patients received 28 evaluable courses at 200, 250, 315, and 390 mg/m2. Severe mucositis limited further dose escalation. Other nonhematological effects included peripheral neuropathy, alopecia, myalgias, arthralgias, nausea, vomiting, diarrhea, and an acute pulmonary reaction that was presumptively due to taxol's Cremophor vehicle. Mean peak taxol plasma concentrations at all dose levels were in the range of concentrations that were previously demonstrated to induce microtubule bundles, a morphological effect associated with cytotoxicity, in leukemia cells in vitro. Pretreatment blasts from 12 patients were incubated with taxol ex vivo. Taxol-induced microtubule bundles were apparent in the blasts of eight patients who also had cytoreduction of tumor, and sensitivity to bundle formation was related to the magnitude of antitumor activity. In contrast, taxol did not induce microtubule bundles ex vivo in the blasts of the other four total nonresponders. Based on this study, the maximum tolerated doses and recommended Phase II doses for taxol, limited by nonhematological toxicity and administered as a 24-h i.v. infusion to patients with refractory leukemias, are 390 and 315 mg/m2. Phase II trials at these myelosuppressive doses are required to determine taxol's activity in the treatment of leukemias. In addition, further evaluation of microtubule bundle formation ex vivo in Phase II studies is necessary to determine the ultimate utility of this assay in assessing tumor sensitivity to taxol.
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PMID:Phase I and pharmacodynamic study of taxol in refractory acute leukemias. 256 75

Iproplatin was administered intravenously over 30 min daily for 5 consecutive days every 3 weeks to 80 evaluable patients with a variety of refractory solid tumor malignancies. Thrombocytopenia was the dose-limiting toxicity. Reversible drug-induced renal dysfunction was observed in 3 patients. One patient sustained mild ototoxicity but neurotoxicity was not encountered. Transient neutropenia, anemia, nausea, vomiting, diarrhea, elevations of liver enzymes, alopecia, and skin rash also occurred. The spectrum and severity of toxicity of iproplatin were found to differ from those of cisplatin. The maximally tolerated dose (MTD) was 45 mg/m2/day in patients who received prior chemotherapy and 65 mg/m2/day in those who did not. No complete responses occurred. Partial responses were obtained in 2/15 patients with colon cancer, 3/18 with breast cancer, 2/4 with carcinoma of unknown primary site and 1/2 with pancreatic cancer. Thirteen patients with lung (5), breast (4), colon (2), head and neck (1) and cervical (1) cancers had stable disease. Based on the different toxicity profiles between iproplatin and cisplatin and the possible antitumor efficacy of the former, phase II investigation of iproplatin has been initiated.
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PMID:Phase I--preliminary phase II trial of iproplatin, a cisplatin analogue. 319 85

A report on a rare case of pineocytoma is presented. A 27-year-old woman visited our clinic because of a 3-month history of intermittent headaches and nausea. A CT scan revealed the presence of a marked obstructive hydrocephalus and mass without any contrast enhancement in the pineal region. Immediately, V-P shunting was performed and resulted in relief of all symptoms. Ventriculography showed a complete occlusion at the aqueductus Sylvii and filling defect at the posterior part of the 3rd ventricle. The patient was operated on in the prone position via infratentorial supracerebellar approach by suboccipital craniectomy on November 9, 1982. A grayish red-colored, well-defined solid tumor located at the pineal region was removed partially. The histopathological appearance of this tumor resembled the pattern of the normal pineal gland. Many cells exhibited a polar form, eosinophilic cytoplasm with the process often being directed toward a blood vessel. The cells around the central areas occupied by pale eosinophilic material were arranged like a "rosette". Combined chemo-radiotherapy was carried out after surgery. That is, a total dose of 4,825 rads to the whole brain was irradiated, and ACNU 140 mg and VCR 6 mg in total were administered intravenously and intermittently. After irradiation therapy, the tumor increased in size producing a ring-like enhancement effect as shown on repeated CT scans. During this time, she started to complain of blurred vision with Parinaud's sign. A second operation via interhemispheric approach by right parietal craniotomy was undergone, and the tumor was partially resected again on March 29, 1983.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Pineocytoma--a case report]. 370 49

Aziridinylbenzoquinone is a quinone compound capable of penetrating the central nervous system. It has demonstrated activity against both intracranial and i.p. murine tumors and human tumor xenographs. We have conducted a Phase I trial of aziridinylbenzoquinone in 60 children with advanced cancer who were refractory to conventional therapy. The drug was given by slow i.v. push on a daily schedule for 5 days every 3 to 4 weeks. The dose range explored included 6 dose levels, ranging from 6 to 12 mg/sq m daily for 5 days in patients with solid tumors and leukemia, and in patients with leukemia, 20, 25, and 30 mg/sq m daily for 5 days. Myelosuppression was the dose-limiting side effect. In patients with solid tumor the highest dose studied was 12 mg/sq m, and the median nadir white blood cell and platelet counts were 0.7 X 10(3) and 6.0 X 10(3)/microliter on Days 17 and 22, respectively. The median recovery day for white blood cells was 39. There may be some evidence of cumulative toxicity with prolonged thrombocytopenia. Other side effects were mild nausea, vomiting, and mucositis. Elevations in liver enzymes and bilirubin were transient and dose dependent, occurring 3 to 4 weeks after drug administration. Of the 34 children with solid tumors, 33 were evaluable for hematopoietic toxicity, 3 were early deaths, and 31 receiving a total of 55 courses were evaluable for therapeutic response. Partial responses lasting 3 weeks to 6 months were seen in the 4 patients with Hodgkin's disease, and in a child with a metastatic spinal cord ependymoma. Fifty-two courses were given to 9 patients with acute lymphocytic leukemia and 17 with acute nonlymphoblastic leukemia. Of the 15 patients with acute nonlymphoblastic leukemia treated at doses greater than or equal to 25 mg/sq m/day for 5 days there was one early death and there were 2 M1 (less than or equal to 5% blasts with normal cellularity), 3 M2A (6 to 15% blasts), and 2 M2B (16 to 39% blasts) bone marrow responses lasting 1 to 3.5 months. Aziridinylbenzoquinone demonstrated activity against acute nonlymphocytic leukemia with maximal tolerated doses of 30 mg/sq m daily for 5 days. Its effect in Hodgkin's disease is encouraging; however, further study will be required to determine its efficacy in central nervous system cancers. Recommended doses for Phase II studies, using daily schedule for 5 days in children with solid tumors, is 9 mg/sq m, and in children with leukemia, it is 25 mg/sq m.
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PMID:Phase I study of aziridinylbenzoquinone (AZQ, NSC 182986) in children with cancer. 669 81

Pentamethylmelamine (PMM), a demethylated soluble analog of hexamethylmelamine, was given to 35 patients with solid tumors in a phase I clinical trial. Thirty patients were given single doses ranging from 80 to 2000 mg/m2 in a 2-hour infusion every 3 weeks. Once a maximum tolerated dose was defined for this schedule, an additional five new patients plus four patients who had already received PMM were treated on a multiple-dose schedule of PMM given three times a week every Monday, Wednesday, and Friday (M-W-F) for 4 weeks. Dose-limiting toxic effects for the single-dose schedule were in the central nervous system and gastrointestinal tract, manifested by nausea (60%), vomiting (49%), somnolence (37%), depression (6%), and headache (6%). Other toxic effects observed on this schedule included anorexia (34%), diarrhea (7%), and diaphoresis (21%). The toxic effects were first observed in mild form at 400 mg/m2/dose and became progressively more severe and prolonged with each dose escalation; they were considered intolerable at the 2000-mg/m2 dose level in all patients treated. The nine patients receiving the multiple-dose schedule were given PMM at a dose of 1000 mg/m2 three times a week (M-W-F). This level produced dose-limited nausea and vomiting in all patients so that no patient completed greater than 3 weeks of treatment on this schedule. One patient developed PMM-related visual hallucinations. PMM produced no hematologic, hepatic, renal, allergic, or acute side effects; no alopecia was observed. Minor tumor regressions of 1 month's duration were seen in two patients, one with pleural mesothelioma and one with a parotid gland tumor. The recommended doses for solid tumor phase II studies are 1500 mg/m2 given as a 2-hour infusion every 3 weeks and 1000 mg/m2 given three times a week (M-W-F), repeated at 3-week intervals.
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PMID:Phase I trial of pentamethylmelamine in patients with previously treated malignancies. 678 47

Aclacinomycin A (ACM-A), an anthracycline analog, was given to 17 patients with solid tumors and to one patient with multiple myeloma, in a phase I clinical trial. A single dose of 60-120 mg/m2 was given every 3 weeks. Dose-limiting toxicity was myelosuppression, especially thrombocytopenia. Granulocytopenia was variable and did not always recover by Day 21 in time for the next ACM-A treatment. Other toxic effects were nausea, vomiting, urticaria, and elevation of hepatic enzymes. Alopecia was not a side effect, even in patients receiving multiple courses of ACM-A. Nine patients were monitored with 24-hour continuous ECG recordings (Holter) on 19 ACM-A treatment days. The incidence of premature atrial and ventricular beats was significantly increased following ACM-A administration. In addition, one patient developed episodes of high-degree atrioventricular block and complete heart block after each of four ACM-A doses, necessitating the insertion of a pacemaker. No antitumor responses were seen in the ten patients who had measurable disease and who had received two or more courses of ACM-A. The recommended doses for solid tumor phase II studies are 100 mg/m2 as a single dose every 4 weeks for patients with high performance status and minimal prior chemotherapy and 60 mg/m2 every 4 weeks for all other patients. Until the acute cardiac effects of ACM-A are further understood, we recommend that all patients receiving ACM-A be monitored by ECG recordings.
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PMID:Phase I trial of aclacinomycin A. 695 61

KW2083 7-N-(p-hydroxyphenyl) mitomycin C is a mitomycin C derivative, but not its masked compound. KW2083 differs from mitomycin C in various points. A phase I study of KW2083 by single intravenous injection was performed in 21 patients with advanced solid tumor. The dose limiting factor of this drug is marrow depression, and 70mg/m2 causing marked thrombocytopenia was determined as maximum tolerated dose. The thrombocyte count and the WBC count reached to nadir the minimum 2 to 3 weeks after and 1 to 2 weeks after the administration and recovered in 1 to 2 weeks and in 2 to 3 weeks respectively. As gastrointestinal symptoms, nausea or vomiting (38.1%), and anorexia (28.6%) occurred soon after the administration, and stomatitis and diarrhea were also observed in one case each. In addition, petechia, hemorrhagic tendency and fever were found in one case each. Patients receiving 70mg/m2 showed slight alopecia and transient slight in GOT and GPT elevation.
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PMID:[Phase I study of KW2083 7-N-(p-hydroxyphenyl) mitomycin C]. 718 79


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