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)

Etoposide (VP 16) is a semi-synthetic derivative of 4'- demethylepipodophyllotoxin , a naturally occurring compound synthesized by the North American May apple (Podophyllum peltatum ) and the Indian species Podophyllum emodi Wallich . Although podophyllotoxins are classical spindle poisons causing inhibition of mitosis by blocking mitrotubular assembly, etoposide inhibits cell cycle progression at a premitotic phase (late S and G2), probably via inhibition of DNA synthesis. There appears to be a selective antileukemic dose response relationship when compared to normal hematopoietic elements. Etoposide is effective when administered orally at about twice the recommended parenteral dosage. Schedule dependency in both animal models and clinical trials has been observed; multiple dosing over three to five consecutive days is superior to weekly single dose administration. Etoposide's dose-limiting toxicity is myelosuppression (leukopenia), which is quite predictable; alopecia and Gl toxicity (nausea, vomiting, stomatitis) occur in about 20-30% of patients given recommended dosages. Etoposide appears to be one of the most active drugs for small cell lung cancer, testicular carcinoma (the Food and Drug Administration approved indication), ANLL and malignant lymphoma. Etoposide also has demonstrated activity in refractory pediatric neoplasms, hepatocellular, esophageal, gastric and prostatic carcinoma, ovarian cancer, chronic and acute leukemias and non-small cell lung cancer, although additional single and combination drug studies are needed to substantiate these data. Its contribution in front-line combination chemotherapeutic regimens for these cancers will be better defined in the forthcoming years. Etoposide appears to have minimal activity in breast cancer and, based on current data, it is inactive against malignant melanoma, colorectal adenocarcinoma and cancer of the head and neck, although the dosage and schedules used in many of the Phase II studies may have been suboptimal.
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PMID:Etoposide: a semisynthetic epipodophyllotoxin. Chemistry, pharmacology, pharmacokinetics, adverse effects and use as an antineoplastic agent. 632 63

28 consecutive patients (age 15-58 years) with refractory acute leukaemia (24 AML, 4 ALL) have been treated with high or intermediate dose cytosine arabinoside (AraC). Twenty patients received AraC at a dose of 3000 mg/m2, twice daily for 6 days (13 patients AraC alone, 7 patients AraC and doxorubicin) and 8 patients received AraC at a dose of 1000 mg/m2, twice daily for 6 days and daunorubicin. 10 of the 20 patients treated with high dose AraC achieved a complete remission (50%) and 2 a partial remission. No patients in the intermediate dose AraC group achieved a remission (p = 0.05). Toxicity of these protocols was acceptable. Vomiting, headache, somnolence, fever, conjunctivitis, and minor cardiac arrhythmias were found most frequently. The pancytopenic period ranged from 16-30 days for the high dose protocol and 14-23 days for the intermediate dose protocol. Sophisticated isolation and blood banking facilities are required in this period. Median duration of remission was 6 months. Results obtained are in favour of the high dose protocol in refractory leukaemia. Only a large dosage increment of AraC can overcome refractoriness of leukaemic blast cells.
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PMID:Experience with intermediate and high dose cytosine arabinoside in refractory acute leukaemia. 635 50

The toxic effects of high-dose busulfan (16 mg/kg) and cyclophosphamide (200 mg/kg) with autologous or syngeneic bone marrow rescue were evaluated in 19 patients (11 with acute myelocytic leukemia, one with acute lymphocytic leukemia, one with acute myelofibrosis, two with chronic myelocytic leukemia, one with Hodgkin's disease, and three with non-Hodgkin's lymphoma). Their mean age was 26 years (range, 6-50); nine patients had syngeneic and ten had autologous bone marrow rescue (six of whom had in vitro bone marrow incubation with 4-hydroperoxycyclophosphamide). Severe myelosuppression was expected and was seen in all patients; leukocyte and platelet count recovery occurred at a median of 19 days (range, 11-59) and 30 days (range, 20-89), respectively. Nausea, vomiting, and diarrhea were frequent but readily managed with vigorous medical therapy. Stomatitis was severe in 14 patients. Skin, renal, cardiac, pulmonary, and CNS complications directly attributable to drug-related toxic effects were transient and non-life-threatening. Hepatic function abnormalities were common but tended to be transient. Most patients tolerated high-dose busulfan and cyclophosphamide with manageable side effects. Hepatic veno-occlusive disease was fatal in two patients, while diffuse interstitial pneumonitis with disseminated herpes virus infection was fatal in three patients with lymphoma. All patients treated in relapse or without previous therapy had a complete tumor response. Further studies with this regimen should be pursued.
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PMID:Preliminary results of high-dose busulfan and cyclophosphamide with syngeneic or autologous bone marrow rescue. 637 4

Twelve patients with refractory acute leukemia (7 patients with acute myelocytic leukemia and 5 patients with acute lymphocytic leukemia) were treated with a new anthracycline antibiotic, aclacinomycin-A (ACM). ACM was administrated by intravenous drip infusion at a dose of 20 mg/day for 7 or 14 days and this was repeated after at least 7 days. Four of 12 patients (33.3%) achieved a complete remission; 3 of 7 acute myelocytic leukemia (42.8%) and 1 of 5 acute lymphocytic leukemia (20.0%). The days required for achieving the complete remission ranged from 23 to 78 days (median: 61) and the total doses of ACM used from 180 to 500 mg (median: 310), and the durations of complete remission from 11 to 28+ weeks (median: 21+). The untoward effects on digestive organs, such as nausea, vomiting and anorexia, and hematological toxicities were frequently seen; however, they were controlled by supportive treatment. Alopecia was not observed. Arrythmia was recognized in one patient at the initiation of ACM infusion with complete remission without withdrawal of ACM. These results suggest that ACM is a potentially effective anthracycline antibiotic in the clinical management of acute leukemia.
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PMID:Treatment of refractory acute leukemia with aclacinomycin-A. 644 34

Aclarubicin (ACM) was administered as induction treatment to 40 patients with acute myeloid leukemia (AML) who were either refractory to initial induction chemotherapy or in relapse. Thirty-eight patients with AML, 2-80 years of age (mean +/- SE, 35.0 +/- 3.2), were evaluated during this study. Seventeen of these patients were given ACM after an unsuccessful attempt had been made to attain a complete remission (CR) with various regimens that included doxorubicin or daunorubicin; this group was considered resistant to these drugs. ACM was administered by rapid iv injection. Thirteen patients received a single course of ACM at a daily dose of 10-30 mg/m2 until a maximum total dose of 300 mg/m2 was reached or until unacceptable toxicity appeared. Of these patients, two (15%) attained a CR. The other 25 patients were given 10-day courses of ACM at a daily dose of 15 mg/m2 with 10-day intervals between courses; courses were repeated until the blast cells were cleared from peripheral blood and bone marrow or until progressive disease became evident. With this regimen, 11 patients (44%) attained a CR. The overall CR rate for the 38 patients was 34%. Total doses necessary to achieve a CR ranged from 150 to 600 mg/m2. A CR was attained by six patients who were previously resistant to a regimen containing moderate doses of doxorubicin. The incidence and severity of the toxic effects were related to the dose of ACM administered per course of therapy. The incidence of mucositis, diarrhea, vomiting, and infection in patients who received doses greater than 150 mg/m2/course was significantly higher than that observed in patients who received a dose of 150 mg/m2/course. In the latter patients, toxicity was within acceptable limits. Alopecia was not observed. Three patients had transient T-wave inversion, and reversible atrial flutter developed in one patient. Our results indicate that ACM is a major new drug for the treatment of AML.
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PMID:Phase I-II study of aclarubicin for treatment of acute myeloid leukemia. 658 33

Aclacinomycin A (ACM) was administered for induction treatment to 40 previously treated acute myeloid leukemia (AML) patients. 38 patients aged 2 to 80 years (mean +/- SE, 35.0 +/- 3.2 years) with overt AML were evaluated; of these, seventeen patients were given ACM after an unsuccessful attempt to obtain a complete remission (CR) with various regimens comprising adriamycin (ADM) or daunorubicin (DNR) and were considered resistant to these drugs. Thirteen patients received ACM at a daily dose of 10 to 30 mg/m2 IV bolus until the maximum total dose of 300 mg/m2 per course was reached or until unacceptable toxicity appeared; of these patients, 2 (15%) attained a CR. Twenty-five patients were given 10-day courses of ACM at the daily dose of 15 mg/m2 IV bolus with 10-day intervals between courses; with this regimen 11 patients (44%) attained a CR. The overall CR rate was 34%. Total doses necessary to attain a CR ranged from 150 to 600 mg/m2. CR was attained by 6 patients (35%) of the 17 who were previously resistant to ADM or DNR. The incidence and severity of the toxic effects such as mucositis, diarrhea, vomiting and infection were related to the dose of ACM administered during each course of therapy. However, in patients who received 150 mg/m2 per course the toxicity was within acceptable limits. Alopecia was not observed. Transient T-wave inversion was observed in 3 patients and atrial flutter developed in one patient. Therefore, we conclude that ACM is a new major drug in the treatment of AML.
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PMID:Phase I-II study of aclacinomycin for a treatment of acute myeloid leukemia. 659 62

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

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

High-dose cytarabine (HDARA-C) at doses ranging from 1000 to 3000 mg/m2 administered as 30-min iv infusions was used in 12 patients with acute leukemia. HDARA-C toxicity was marked by nausea, vomiting, and somnolence; fever occurred in one patient. Myelosuppression was brief and reversible; the wbc count nadir occurred between Days 10 and 15 after treatment. In this study of a limited number of patients, no reliable conclusions could be drawn about antileukemic activity. However, (a) HDARA-C appeared to be a well-tolerated regimen in acute myeloblastic leukemia in complete remission; (b) a clear improvement was obtained in a patient with central nervous system leukemia; and (c) a sharp but transient decrease in peripheral blast cell counts was seen in two patients with acute myeloblastic leukemia. Cytarabine distribution was bi- or tri-compartmental; plasma final half-life was greater than 4 hrs in six patients. Pharmacokinetic parameters were not correlated with serum deoxycytidine deaminase activity. HDARA-C crosses the blood-brain barrier and may be useful in the prophylaxis against and treatment of central nervous system leukemia.
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PMID:High-dose cytarabine in acute leukemia: toxicity and pharmacokinetics. 685 Jun 54

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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