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)

cis-Dichlorodiammineplatinum(II) (DDP), at a dose of 15 mg/m2/day x 5 consecutive days, was administered to 68 evaluable patients with metastatic soft tissue and bony sarcomas. All patients, except one, had received extensive prior chemotherapy and had had progressive disease at the start of the study. Responses observed included one complete response in a patient with mesothelioma and three partial responses in patients with soft tissue sarcomas (7%). No responses were seen in 18 patients with bony sarcomas. Significant leukopenia and thrombocytopenia were observed in less than 20% of evaluable courses, although two patients manifested life-threatening leukopenia (less than 1000 cells/microliter) and three had life-threatening thrombocytopenia (less than 24,000 cells/microliter). Nephrotoxicity was noted in less than 25% of evaluable courses. Nausea and/or vomiting was recorded in 55% of evaluable courses. DDP is considered to be marginally active in the secondary treatment of metastatic sarcomas at this dose and schedule. Further studies of DDP in mesothelioma are indicated.
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PMID:Cis-dichlorodiammineplatinum(II) in advanced soft tissue and bony sarcomas: a Southwest Oncology Group Study. 57 67

A 50-year-old female was admitted because of nausea, vomiting, and cerebellar ataxia. Computed tomography scan revealed an enhanced mass accompanied with a cyst in the right cerebellar hemisphere. The mass situated in the subcortical region was removed. Histologically, highly vascular tumor cells lined the cavities. Postoperative radio- and chemotherapy were administered and the clinical symptoms improved gradually. Two months later, the patient complained of dyspnea. Chest X-ray on second admission demonstrated cardiomegaly. Hemorrhagic pericardial effusion amounting to 1000 ml was aspirated by pericardial puncture. Papillary clusters of tumor cells were demonstrated in the pericardial effusion. The patient died of cardiac failure. At necropsy solid tumors were located in the heart, lung, left inguinal region, and cerebellum. Histological diagnosis was mesothelioma arising from the heart. Primary pericardial mesotheliomas are rare; approximately 106 cases have been reported. Pericardial mesothelioma frequently spreads to the adjacent pleura and mediastinum, but distant metastases are extremely rare because patients with pericardial mesothelioma tend to die early due to cardiac failure or cardiac tamponade.
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PMID:[Brain metastasis from primary pericardial mesothelioma. Case report]. 170 70

We performed a phase I trial of CI-937 (DUP937), an anthrapyrazole, with the following objectives: (a) to determine the maximally tolerated dose in humans; (b) to define the toxicity spectrum of this agent; (c) to describe the pharmacokinetics of the drug; (d) to test a pharmacokinetics based hypothesis of dose escalation; and (e) to relate drug pharmacokinetics to pharmacodynamics. CI-937 was administered as a single bolus injection every 3-4 weeks at doses ranging from 3.6 to 25.2 mg/m2. Thirty-two patients and 57 courses were evaluable for toxicity. Pharmacokinetic analysis was performed in 30 patients on the first course using a sensitive and selective radioimmunoassay. The maximally tolerated dose in patients with no prior therapy was 25.2 mg/m2 and dose-limiting toxicity was neutropenia. Thrombocytopenia, nausea, vomiting, stomatitis, and alopecia were mild. A partial response was recorded in a patient with mesothelioma. The area under the curve increased linearly with dose, and total body clearance of CI-937 was independent of dose. The mean total body clearance was 107 +/- 55.8 ml/min/m2, mean steady state volume of distribution was 492 +/- 469 liters/m2, and terminal half-life was 3.78 +/- 2.86 days. The extended factors of 2 methods of pharmacologically guided dose escalation were intended for use but ultimately were equivalent to that of the modified Fibonacci dose escalation method. Dose and the area under the curve were significant predictors of a percentage change in WBC and neutrophil count in a univariate analysis. Only dose and baseline neutrophil count predicted a percentage change in WBCs in a multifactor analysis. Dose and prior chemotherapy predicted percentage change in neutrophil count in a multifactor analysis. We conclude that the dose-limiting toxicity of CI-937 is neutropenia and that the recommended phase II starting dose is 22 mg/m2.
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PMID:Phase I pharmacokinetic and pharmacodynamic study of a new anthrapyrazole, CI-937 (DUP937). 193 93

Ninety-eight patients with previously-treated advanced soft tissue sarcoma, bone sarcoma, or mesothelioma were randomly assigned to one of two intravenous single-agent treatment regimens, either 6-diazo-5-oxo-l-norleucine (DON; brief infusions of 50 mg/m2/day for 5 consecutive days every 4 weeks) or aclacinomycin-A (ACM-A, as 30-min infusions of 100 mg/m2 or 85 mg/m2, administered every 3 weeks). Of 43 patients who were evaluable for response, survival and toxicity, there were two responses (5%) produced by ACM-A; one in a male with mesothelioma, and one in a female with malignant fibrous histiocytoma. None of the 36 evaluable patients treated with DON developed an objective tumor response. Median survival was 4.8 months in the DON treatment arm, and 6.8 months in the ACM-A treatment arm. No patients on the DON arm experienced lethal or life-threatening toxicities, and severe toxicities resulting from this treatment included nausea and emesis (10%), stomatitis (2%), gastrointestinal toxicity (2%), and anemia (2%). Moderate toxicities included vomiting (24%), hematologic toxicity (24%), neurologic toxicity (7%), diarrhea (7%), mucositis (5%), fever (5%), palpitations (2%), hepatotoxicity (2%), bleeding (2%) and edema (2%). Fifteen percent experienced at least one severe reaction, and 63% experienced at least one moderate or greater toxicity. ACM-A was associated with four cases of life-threatening myelosuppression (7%); severe toxicities included myelosuppression (11%), neurologic toxicity (4%), diarrhea (2%), respiratory toxicity (2%), pain and muscle spasms (2%), edema (2%), and ulceration following extravasation (2%).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Phase II trial of 6-diazo-5-oxo-L-norleucine versus aclacinomycin-A in advanced sarcomas and mesotheliomas. 218 26

A Phase I study of intravenous (IV) bolus 4'-0-tetrahydropyranyladriamycin (Pirarubicin) was done in 55 patients in good performance status with refractory tumors. Twenty-six had minimal prior therapy (good risk), 23 had extensive prior therapy (poor risk), and six had renal and/or hepatic dysfunction. A total of 167 courses at doses of 15 to 70 mg/m2 were evaluable. Maximum tolerated dose in good-risk patients was 70 mg/m2, and in poor-risk patients, 60 mg/m2. The dose-limiting toxic effect was transient noncumulative granulocytopenia. Granulocyte nadir was on day 14 (range, 4-22). Less frequent toxic effects included thrombocytopenia, anemia, nausea, mild alopecia, phlebitis, and mucositis. Myelosuppression was more in patients with hepatic dysfunction. Pharmacokinetic analyses in 21 patients revealed Pirarubicin plasma T 1/2 alpha (+/- SE) of 2.5 +/- 0.85 minutes, T beta 1/2 of 25.6 +/- 6.5 minutes, and T 1/2 gamma of 23.6 +/- 7.6 hours. The area under the curve was 537 +/- 149 ng/ml x hours, volume of distribution (Vd) 3504 +/- 644 l/m2, and total clearance (ClT) was 204 + 39.3 l/hour/m2. Adriamycinol, doxorubicin, adriamycinone, and tetrahydropyranyladriamycinol were the metabolites detected in plasma and the amount of doxorubicin was less than or equal to 10% of the total metabolites. Urinary excretion of Pirarubicin in the first 24 hours was less than or equal to 10%. Activity was noted in mesothelioma, leiomyosarcoma, and basal cell carcinoma. The recommended starting dose for Phase II trials is 60 mg/m2 IV bolus every 3 weeks.
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PMID:A phase I study of 4'-0-tetrahydropyranyladriamycin. Clinical pharmacology and pharmacokinetics. 222 62

Malignant peritoneal mesothelioma is an uncommon tumor with great diagnostic and therapeutic problems. Symptoms, clinical features and course of the disease are described in three patients which were seen at our hospital within the last years. At the beginning there are often severe weight loss, malaise and sometimes fever of unknown origin. Abdominal pain, increased abdominal girth or nausea indicate advanced tumor stages in most cases. Ultrasonography and computed tomography of the abdomen can give important information during the diagnostic approach. Nevertheless, the definite diagnosis can only be established by laparoscopy or open surgery with biopsy for a histological examination. Despite intern and extern radiotherapy as well as systemic and/or local chemotherapy the prognosis of malignant peritoneal mesothelioma remains unfavourable. Mean survival time ranges from six to 18 months.
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PMID:[Diagnosis and therapy of malignant peritoneal mesothelioma]. 253 Dec 68

A patient with malignant ascites refractory to conservative and conventional therapy underwent peritoneovenous shunt. The shunt provided palliation for 7 months with relief of nausea, vomiting, and anorexia and with decrease of weight and abdominal girth. There was no need for repeated paracenteses, which had been required before shunting. The patient's strength increased. However, increasing shortness of breath developed approximately 6 to 7 months after insertion of the shunt. The shunt was associated with extensive metastatic dissemination of peritoneal mesothelioma to both lungs. It is suggested that peritoneal mesothelioma is a contraindication for peritoneovenous shunt.
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PMID:Peritoneovenous shunt for intractable malignant ascites. A single case report of metastatic peritoneal mesothelioma implanted via LeVeen shunt. 620 8

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

Twenty-three patients with disseminated bony sarcoma and 23 patients with malignant mesothelioma were evaluable in a Southwest Oncology Group (SWOG) clinical trial utilizing rubidazone and DTIC. One partial remission (PR) was observed in a previously untreated patient with metastatic Ewing's sarcoma. One patient with giant cell tumor of bone had an improvement, short of PR. Thirteen patients with osteogenic sarcoma and 23 with malignant mesothelioma had no response to this combination of drugs. The major toxic effects of therapy included nausea, vomiting, and myelosuppression, especially leukopenia; no cardiac toxicity was noted. We conclude that the combination of rubidazone and DTIC is inactive in bony sarcoma and mesothelioma.
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PMID:Combination chemotherapy for advanced sarcomas of bone and mesothelioma utilizing rubidazone and DTIC: a Southwest Oncology Group Study. 683 8

Because of its unusual mechanism of action, docetaxel was selected for study in advanced soft tissue sarcomas of adults as part of a search for new active antisarcoma agents. Patients at least 18 years old with measurable histologically proven advanced nonosseous sarcomas were enrolled if they had ECOG performance status of < or = 2 and satisfactory leukocyte and platelet counts, and hepatic and renal function. Patients with Kaposi's sarcoma, mesothelioma, meningioma, embryonal rhabdomyosarcoma, and extraosseous Ewing's sarcoma were excluded, as were patients with brain or leptomeningeal metastases. Other specific contraindications to participation included other active cancer, previous or concurrent cancer chemotherapy or immunotherapy, and known allergy to the drug vehicle, polysorbate 80. Women of childbearing potential were required to have a negative pregnancy test. Following premedication with dexamethasone and diphenhydramine hydrochloride, docetaxel 100 mg/m2 as a concentrated solution containing 40 mg/ml in polysorbate 80 was infused over 1 h in 250 ml of either dextrose 5% in water or 0.9% saline. Treatment was repeated at 3-week intervals using standard definitions for objective responses. Up to two separate 25% toxicity directed dose reductions were permitted. Between May and December 1993, nine men and nine women registered (median age, 44 years). They received a total of 51 cycles of docetaxel (median, 2.5 cycles). Toxicity included moderate leukopenia (median first cycle nadir, 1.5 x 10(9)/L) but no significant thrombocytopenia. Alopecia, diarrhea, nausea, vomiting, and anorexia were common side effects. Fever, minor skin rashes, stomatitis, and edema were also observed. One drug-related death occurred in a neutropenic patient. One partial regression was observed (5.9%, 95% C.I. 0.15-28.7%) among the 17 eligible patients in a patient with metastatic uterine leiomyosarcoma.
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PMID:Phase II study of docetaxel in advanced soft tissue sarcomas. 893 74


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