Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Twenty-two evaluable adult patients with relapsed, acute nonlymphocytic leukemia (ANLL) were treated with the combination of amsacrine (m-AMSA) and 5-azacytidine (AZA) as part of an Eastern Cooperative Oncology Group (ECOG) pilot study to evaluate efficacy and toxicity. Each drug was given in a dosage of 150 mg/m2 i.v. daily for 5 consecutive days. A complete response (CR) was obtained in 8 of 22 patients (36%) and a partial response was seen in two others, yielding an overall response rate of 45%. Median survival for all 22 patients was 2.5 months, but medium survival was 7.2 months (range 4.3-13 months) for those with a CR. Twelve of 22 died during the first 3 months, seven of these during the period of drug-induced aplasia. Moderate to severe toxicity included serious infection (16 of 22); nausea, vomiting, and diarrhea (19 of 22); and mucositis (10 of 22). There were four instances each of cardiac abnormalities and hepatic abnormalities but all reversed spontaneously. We conclude that this combination therapy cannot be recommended for further investigation in relapsed patients with ANLL since there was no notable increase in long-term survival and since there were 10 treatment-related deaths out of 22 patients.
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PMID:Amsacrine [4'-(9-acridinylamino)-methanesulfon-m-anisidide] (m-AMSA) and 5-azacytidine (AZA) for remission reinduction in patients with relapsed adult acute nonlymphocytic leukemia. An ECOG pilot study. Eastern Cooperative Oncology Group. 243 42

A series of 46 patients with acute leukaemia were treated with amsacrine (m-AMSA) and cytosine arabinoside (ara-C). Complete remission (CR) was achieved in 15 of 38 (40%) patients with acute myelogenous leukaemia (AML) and 4 of 8 (50%) patients with acute lymphoblastic leukaemia (ALL). The CR rate was significantly higher (P less than 0.05) for the younger, previously treated patients with AML (9/16) than for the older previously untreated ones (6/22), because of higher treatment mortality in the latter group. Myelosuppression was prolonged and profound. Major nonhaematological toxicity affected the gastrointestinal tract (nausea, vomiting, mucositis, bleeding and ileus associated with severe diarrhoea). Many patients also developed reversible hepatic dysfunction and two elderly patients died of cardiac arrhythmia. Further trials of this combination are justified in patients with relapsed or resistant leukaemia, but for older patients dose reduction is recommended.
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PMID:Treatment of acute leukaemia with m-AMSA in combination with cytosine arabinoside. 346 35

Amsacrine and high-dose cytarabine (HiDAc), when administered as single agents, are effective treatment of acute leukemia. When used in combination, a high remission rate is also possible. We treated 47 patients with acute myelogenous leukemia (AML), acute lymphoblastic leukemia (ALL), and blastic phase of chronic myelogenous leukemia (CML) with a combination of amsacrine and HiDAc. The patients received amsacrine 200 mg/m2 daily for three days and, concurrently, HiDAc 3 g/m2 over three hours once daily for five days. Of 20 evaluable patients with AML in relapse, there were 12 remissions; of seven additional patients with primary refractory AML, there were two remissions, and of 12 patients with ALL in relapse, there were eight remissions. The three patients with blastic phase CML and the three patients with biphenotypic leukemia did not respond. Nausea, vomiting, stomatitis, hepatic dysfunction, and diarrhea were common, but cutaneous, conjunctival, and significant cerebellar and cerebral side effects were absent. We conclude that this regimen is highly effective therapy for AML and ALL and is also safe, eliminating the major toxicities encountered with HiDAc.
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PMID:A new regimen of amsacrine with high-dose cytarabine is safe and effective therapy for acute leukemia. 354 13

Amsacrine, an antineoplastic agent currently undergoing clinical trials in the U.S., has been shown to be active against adult and pediatric leukemias, Hodgkin's disease, and non-Hodgkin's lymphomas. Amsacrine is highly bound to plasma proteins and is eliminated primarily via hepatic metabolism. Severe hepatic dysfunction will result in a decreased excretion rate of the drug. The primary side effect is a dose-related suppression of bone marrow function. Other reported toxic effects include mucositis, nausea, vomiting, cardiotoxicity, liver dysfunction, and alopecia. Despite these negative effects, amsacrine appears to have a role in the combination therapy of acute leukemias.
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PMID:Amsacrine evaluation. 355 46

A total of 70 patients with malignant lymphomas refractory to one or more chemotherapeutic regimens were treated with iv amsacrines (m-AMSA and m-AMSA lactate). Of 58 evaluable patients, 12 had Hodgkin's disease and 46 had non-Hodgkin's lymphoma. Twenty-nine of the evaluable patients received m-AMSA and 29 received m-AMSA lactate. The amsacrines were recycled every 3 weeks. The doses of m-AMSA were 90-120, 70, and 25-30 mg/m2/day for 3 days, respectively. All patients treated with m-AMSA lactate received a single dose of 225 mg/m2. In Hodgkin's disease, the response rate was 58.3% (one complete response among 12 patients), and in non-Hodgkin's lymphoma, the response rate was 30.4% (six complete responses among 46 patients). The median duration of response was 3 and 5 months, respectively. The response rate was unfavorably affected by the presence of extra-nodal disease and a Karnofsky performance status less than 80. There was no important difference in the incidence and duration of response between m-AMSA and m-AMSA lactate. After vomiting, myelosuppression was the most frequent observed toxic effect. One patient showed an unexpected fatal bone marrow aplasia following the first course of 90 mg/m2. This study indicates that m-AMSA and m-AMSA lactate are active and moderately toxic in previously treated malignant lymphomas. Thus, amsacrines could be effectively incorporated into salvage polydrug regimens.
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PMID:Phase II study with amsacrines (m-AMSA and m-AMSA lactate) in refractory lymphomas. 383 14

27 patients (aged 15-55 years) with relapsed acute myelogenous (AML) and lymphoblastic leukaemia (ALL), and with lymphoblastic non Hodgkin's lymphoma (NHL) have been treated with intermediate dose cytosine arabinoside (AraC, 1 g/m2 q 12 h X 12) and 3 d of m-AMSA (20 patients), 90-115 mg/m2 daily, or daunorubicin (7 patients). 18 of them attained a complete remission (AML 10/14, ALL 3/5, NHL 5/8). 7 patients received consolidation treatment with 1-2 courses comprising 4 d of AraC (3 g/m2 q 12 h X 8) and m-AMSA (90-115 mg/m2) on d 5 of each course. 2 patients underwent allogeneic bone marrow transplantation and 9 received no further treatment after remission induction. In addition to vomiting, fever and conjunctivitis, toxicity in 6 patients included a combination of severe diarrhoea, fever and signs of paralytic ileus. 3 of them died during the pancytopenic phase. The pancytopenic period ranged from 16-25 d (median 21 d) after the remission induction and 14-21 d (median 19 d) after the consolidation course. Median remission duration was 5 months for those patients who received no treatment after remission induction and greater than 9 months (4+ - 16+ months) for the patients who received consolidation courses. Increased dosages of AraC are active in relapsed leukaemia and lymphoma, although optimal dose and schedule are still undetermined.
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PMID:Intermediate and high-dose ARA-C and m-AMSA (or daunorubicin) as remission and consolidation treatment for patients with relapsed acute leukaemia and lymphoblastic non-Hodgkin lymphoma. 385 71

10 adult patients (age 27-62 years) with refractory or relapsed acute nonlymphocytic leukemia were treated with high dose cytosine arabinoside (HDAraC: 3 g/m2 q 12 h by IV infusion, d 1-6) either alone (7 patients) or with additional treatment, consisting of bone marrow transplantation (1 patient), m-AMSA (1pt.) and VP16 (1 patient). All patients had received conventional dose AraC (CDAraC); 8 patients were resistant to CDAraC, having failed 1 or more courses of CDAraC just before treatment with HDAraC. Recovery of granulocyte count (0,5 X 10(9)L) occurred at a median of 26 d (23-27 d) after initial therapy, and recovery of platelet counts (50 X 10(9)/L) at a median of 24 d (22-27 d). 6 patients became severely septic, 3 of them requiring granulocyte transfusions. Consequently, sophisticated blood banking facilities and supportive care are required. The non-myeloid toxicities associated with HDAraC were not severe. Vomiting (9/10), erythematous skin rash (4/10), conjunctivitis and photophobia (2/10) were found most commonly. CNS-toxicity, pulmonary toxicity or drug fever were not observed. 4 patients achieved a complete remission and 1 a partial remission. 2 patients failed to respond and 3 patients died during the period of pancytopenia. Thus, HDAraC is effective treatment for refractory or relapsed ANLL, even in cases of apparent resistance to CDAraC.
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PMID:[High-dose cytosine arabinoside in the treatment of recurrent or acute refractory myeloid leukemias]. 388 19

The pharmacology, chemistry, pharmacokinetics, clinical studies, and adverse effects of amsacrine, an investigational antineoplastic agent, are reviewed. Amsacrine's mechanism of action is not clearly understood, although the drug is known to inhibit DNA synthesis. As an investigational NCI "Group C" agent, amsacrine is available to physicians for the treatment of adult patients with refractory acute nonlymphocytic leukemia (ANLL) under an established protocol. Following intravenous administration, amsacrine has a biphasic plasma clearance. It is extensively metabolized by the liver to inactive compounds that are excreted in the bile. Phase I studies indicated that amsacrine was potentially effective in patients with solid tumors and acute leukemias. Patients with solid tumors could tolerate much lower doses of amsacrine than leukemia patients because of dose-limiting bone-marrow suppression in the former. In Phase II studies, amsacrine appeared effective in treating the acute leukemias, with response rates of 31% and 23% for acute lymphocytic leukemia and ANLL, respectively. Patients with other types of cancers have not responded to amsacrine therapy. Frequently occurring adverse effects of amsacrine include leukopenia and thrombocytopenia in patients with solid tumors; nausea, vomiting, and diarrhea; mucositis in patients receiving higher doses (leukemia patients); alopecia; hepatotoxicity; and phlebitis. The clinical usefulness of amsacrine appears limited to treatment of the acute leukemias. Studies of combination therapies that include amsacrine are currently underway and should further define the therapeutic role of amsacrine.
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PMID:Review of amsacrine, an investigational antineoplastic agent. 676 91

m-AMSA is a synthetic aminoacridine DNA intercalator found to have experimental murine antitumor activity. A phase I investigation was undertaken in 71 patients with solid tumors and acute leukemia. Using an intermittent every 3-week schedule in solid tumors, toxicity encountered was primarily hematologic, predominantly leukopenia with relative platelet sparing. The recommended dose for phase II evaluation in patients with solid tumors is 90 mg/m2 every 3 weeks; patients with minimal prior therapy could be treated at 120 mg/m2 and patients with hepatic dysfunction or marginal bone marrow reserve should have an initial dose reduction to 70 mg/m2. Therapeutic activity was seen in Hodgkin's disease, hepatoma, and epidermoid carcinoma of the esophagus. Various dose schedules were studied in leukemia. The recommended dose for phase II evaluation is 120 mg/m2 daily for 5 days as a daily 30-minute infusion. At this dose, nausea, vomiting, mucositis, alopecia, and hepatic toxicity were noted. Therapeutic activity was seen in AML, blastic CML, and CLL. Further clinical trials with this agent are warranted.
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PMID:Phase I study of m-AMSA in patients with solid tumors and leukemias. 689 83


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