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)

Sixteen patients with disseminated squamous cell carcinoma of the lung and 26 patients with adenocarcinoma of the colon and rectum were given rubidazone. Only one partial remission was observed in a previously untreated patient who had local recurrence of a rectal adenocarcinoma. The main toxic effects observed in previously treated patients consisted of leukopenia and thrombocytopenia. Also observed were anorexia, nausea, vomiting, alopecia, fever, and chills. Cardiotoxicity was observed in one patient after a total dose of 720 mg/m2 of rubidazone. It is concluded that rubidazone is a relatively inactive compound in the management of these two diseases.
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PMID:Clinical trial of rubidazone in advanced squamous cell carcinoma of the lung and adenocarcinoma of the large intestine. 36 Dec 29

4'-(9-Acridinylamino)methanesulfon-m-anisidide (m-AMSA, NSC 249992), an acridine derivative, was given to 28 patients with solid tumors and one patient with Hodgkin's disease in a Phase I clinical trial. The dose schedule used was a single dose given every 14 days for three doses. The amount given ranged from 10 to 120 mg/sq m/dose. Dose-limiting toxicity was moderate to severe leukopenia which occurred at and above 70 mg/sq m. Thrombocytopenia was infrequent and did not require transfusion. Nonhematological side effects were mild and included nausea, vomiting, local irritation, and fever. Antineoplastic activity was noted in liposarcoma, adenocarcinoma of unknown primary origin, and squamous carcinoma of unknown primary origin (one patient each). Pharmacokinetics studies were done in 19 patients. Total m-AMSA and free m-AMSA concentrations showed a biphasic distribution with an initial rapid phase of t1/2 = 10 to 15 min for both, and a second slow phase of t1/2 = 8 to 9 hr for total m-AMSA and 3 hr for free m-AMSA. Phase II studies with m-AMSA, in hematological cancers are warranted, since its most consistent effect is on leukocytes. The recommended dosages for solid-tumor Phase II studies are 70 mg/sq m for good-risk patients and 50 mg/sq m for poor-risk patients, given as a single dose every other week, or 120 mg/sq m for poor-risk patients for the single-dose every-3-week schedule.
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PMID:Phase I clinical and pharmacological study of 4'-(9-acridinylamino)-methanesulfon-m-anisidide using an intermittent biweekly schedule. 47 24

N-(Phosphonacetyl)-L-aspartic acid, an inhibitor of aspartate transcarbamylase, was administered to 25 patients with advanced cancer by 10-minute infusion daily x 5 consecutive days to determine the toxicity and to look for evidence of therapeutic effect. Planned dose escalations ranged from 100 to 1250 mg/m2 (daily dose). Nausea, vomiting, and diarrhea were the most frequent toxic effects, with three of six patients treated at a daily dose of 1250 mg/m2 having severe diarrhea. Other toxic effects were encountered rarely and were not dose-limiting; these included mild leukopenia, thrombocytopenia, rash, stomatitis, and increases in SGOT. One patient with a widely metastatic carcinoid of unknown origin had an objective response lasting 6 weeks.
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PMID:Phase I study of N-(phosphonacetyl)-L-aspartic acid (PALA). 52 23

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

In the present discussion, the author summarized the toxicological and biological features of thirty kinds of trichothecene mycotoxins which are produced by a wide range of Fusarium, Myrothecium and others. The 12, 13-epoxytrichothecenes induce nausea, emesis, vomiting, skin inflamation, leukopenia, diarrhea, hemorrhage in lung and brain, and destruction of bone marrow. Since these toxicological characteristics coincide with a major symptom of intoxicated humans and farm animals induced by consumption of moldy cereals and feeds, the red-mold toxicosis and bean-hulls poisoning in Japan, moldy corn toxicosis in U.S.A., A.T.A., stachybotryotoxicosis and dendrochiotoxicosis in Europe, are originated from a common toxicant, trichothecenes. Orally administered trichothecenes are rapidly absorbed and eliminated into the feces and urine upon deacetylation at C-4 by the microsomal esterase of liver. Biochemical approaches to the mode of action revealed that the trichothecenes are a potent inhibitor of protein and D.N.A. syntheses in eukaryotic cells. Bindings to the eukaryotic polysomes and ribosomes and the subsequent inactivation of ribosomal cycle is responsible for their inhibitory effect to initiation and termination reactions. Microbial approaches revealed that the trichothecenes are mutagenic to yeast cells, but are negative in D.N.A.-attacking ability to Bacillus subtilis and reversion assay with Salmonella typhimurium. Reactivity of the epoxide ring of trichothecenes with S.H.-group of proteins will be discussed in relation to the molecular mechanism of action.
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PMID:Mode of action of trichothecenes. 61 39

Poly IC, stabilized with poly-L-lysine and carboxymethyl cellulose (poly ICLC), resists hydrolysis by primate serum (unlike the parent compound), induces high levels of serum interferon, and is effective in acute viral infections of subhuman primates. In a phase I-II clinical trial, poly ICLC was given iv in 15 daily doses of 0.5-27.0 mg/m2 to 19 patients with various solid tumors and to six patients with acute leukemia (1-65 years of age). At least three complete trials were conducted at each of six dose levels. Toxic reactions included fever (in 100% of trials), nausea (44%) hypotension (28%), thrombocytopenia and leukopenia (68%), erythema (12%), and polyarthralgia plus myalgia (16%). Hypotension and arthralgia-myalgia were related to dose level and/or magnitude of interferon induction, but other toxic manifestations were not. Poly ICLC induced significant serum interferon levels in 76% of trials, and the correlation between dose and peak interferon titer was linear. The maximum tolerated dose for all patients at a given drug dose was 12 mg/m2; at this dose, the mean peak interferon titer was 1940 reference units/ml. At a dose of 18 mg/m2, the mean peak interferon titer was 4473 reference units/ml, but severe myalgia and arthralgia were intolerable in at least half of the patients, and most had significant hypotension. At a dose of 27 mg/m2, one patient had acute renal failure. At high doses, iv poly ICLC also induced interferon in the cerebrospinal fluid.
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PMID:Phase I-II trials of poly IC stabilized with poly-L-lysine. 72 10

In a phase I study, the best antitumor/toxicity ratio for DTIC was reported to be at a dose of 250 mg/m2/day X 5 repeated at 28-day intervals. Nausea, vomiting, leukopenia, and thrombocytopenia were the major toxic effects noted. The best responses were seen in disseminated melanoma (19%), various sarcomas (22%), and Hodgkin's disease. A subsequent phase II study in refractory lymphomas showed a response rate in Hodgkin's disease of 56%. In disseminated melanomas, DTIC was then combined with vincristine and BCNU and demonstrated a response rate of 23% which did not improve with the addition of chlorpromazine (23%). A response rate of 31% was seen with the combination of DTIC, BCNU, and hydroxyurea which did not improve with the addition of vincristine (30%). Responders had a more significant survival rate as compared to nonresponders.
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PMID:DTIC (NSC-45388) studies in the southwest oncology group. 76 72

Phase II chemotherapy trials of dianhydrogalactitol and VP-16-213 were conducted in patients with metastatic colorectal cancer who had measurable malignant disease which served as indicators of response to therapy. Dianhydrogalactitol was given in a 5-day course at a dosage of 30 mg/m2/day. Toxic reactions included nausea, vomiting, leukopenia, thrombocytopenia, and anemia. There was a definite tendency to a compounding of hematologic toxicity with repeated courses. No evidence of objective therapeutic response was observed among 30 patients treated. VP-16-213 was given at a dosage of 130 mg/m2 on Days 1, 3, and 5. Toxic reactions included nausea, vomiting, alopecia, leukopenia, thrombocytopenia, and anemia. Hematologic toxicity was more severe in patients with elevated serum bilirubin levels. No evidence of objective therapeutic response was observed among 28 patients treated.
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PMID:Phase II studies of dianhydrogalactitol and VP-16-213 in colorectal cancer. 79 47

Trimethylcolchicinic acid methyl ether d-tartrate (TMCA; NSC-36351) was administered daily by mouth to 71 patients with malignant lymphomas. Partical (greater than 50%) responses were observed in eleven of 37 patients with Hodgkin's disesse, two of 22 patients with lymphocytic lymphoma, and one of two patients with mixed cell lymphoma. One complete and three partial responses were noted in nine patients with histiocytic lymphoma. Responses lasted from one to 91+ months (median: four months) and occurred in patients whose disease was resistant to alkylating agents, vinblastine, vincristine, procarbazine, prednisone or BCNU. Toxic effects included leukopenia, thrombocytopenia, nausea, diarrhea, stomatitis, alopecia and dermatitis.
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PMID:Effect of trimethylcolchicinic acid methyl ether d-tartrate (TMCA) on Hodgkin's and non-Hodgkin's lymphoma. 79 48

Tamoxifen (NSC-180973), a synthetic antiestrogen, was studied for efficacy and toxicity in patients with metastatic breast adenocarcinoma. Two dose levels were used, 10 mg bid and 15 mg/m2 bid, in separate groups. In the 10-mg bid dosage group, 30 of the 31 patients were considered evaluable for efficacy. Five complete and 11 partial responses were recorded, for an overall response rate of 53%. In the 15-mg/m2 bid dosage group, 44 of the 45 patients were considered evaluable for efficacy. Three complete and 16 partial responses were recorded, for an overall response rate of 43%. All 76 patients were evaluated for toxicity. Side effects were generally mild, consisting mostly of hot flushes, transient leukopenia, transient thrombocytopenia, nausea, and fluid retention. A high degree of correlation between response and positive estrogen-receptor assay suggests the value of the test as a means to select patients for tamoxifen treatment. The conclusion from this study is that tamoxifen used as a single agent is an effective drug with minimal toxicity for treatment of metastatic breast adenocarcinoma.
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PMID:Phase II study of tamoxifen: report of 74 patients with stage IV breast cancer. 79 26


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