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)

Clinical studies involving 5-azacytidine, a ring analogue of cytidine, began in Europe in 1967 and the United States in 1970, and we review available preclinical and clinical studies here. The drug possesses cytotoxic, antimicrobial, antineoplastic, abortive, and mutagenic activity in various biological systems. 5-Azacytidine is thought to exert its antineoplastic effect through interference with nucleic acid metabolism. The dose-limiting toxicities are nausea, vomiting, and leukopenia, while the incidence of thrombocytopenia is low. Hepatic toxicity ranges from abnormal findings in liver function tests to hepatic coma. Clinical results in solid tumors are not encouraging, but 5-azacytidine shows consistent antitumor activity in patients with acute myelogenous leukemia resistant to previous treatment. An overall response rate of 36%, with 20% complete remissions, was achieved in 200 previously treated patients with acute myelogenous leukemia. Further studies must define the role of 5-azacytidine alone and in combination for the first-line treatment of acute myelogenous leukemia.
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PMID:5-Azacytidine. A new anticancer drug with effectiveness in acute myelogenous leukemia. 6 73

A 7-year-old boy, having had headache and vomiting for one month, was operated for a tumour in the left side of the posterior fossa. The tumour, weighing 52 g, infiltrated the dura mater, leptomeninges, and also, superficially, the left cerebellar hemisphere. The patient died five weeks after operation. Light and electron microscopical examination revealed a granulocytic sarcoma (chloroma). Pre- and postoperative blood examinations, together with postoperative and autopsy bone marrow examinations, showed no sign of acute myelogenous leukaemia. This is the second reported case of primary intracranial chloroma with no preceding sign of acute myelogenous leukemia, and the first case with cerebellar infiltration.
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PMID:Granulocytic sarcoma (chloroma) of the cerebellum and meninges a case report. 28 6

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

Homoharringtonine (HHT) is one of several cephalotaxine alkaloids that has shown clinical efficacy in patients with acute myelogenous leukemia (AML). In a phase I trial we evaluated cytarabine 100 mg/m2 by continuous infusion daily for 7 days in combination with four dose levels of HHT ranging from 1.5-5 mg/m2 by continuous infusion daily for 7 days to see if an effective regimen could be developed. Twenty-two patients with relapsed and/or primary refractory AML were treated. Seventeen males and five females were treated, with a median age of 40 years (range 19-63). There were five remissions in 14 patients with relapsed AML and none of eight responders in patients with primary refractory AML. None of the three patients treated at 1.5 mg/m2 dose level of HHT responded. Of three patients treated at the 3 mg/m2 dose level, there was one complete remission. At both 4 mg/m2 and 5 mg/m2, two of eight patients achieved complete remission. Four of the five remissions occurred in patients with acute promyelocytic leukemia. Drug induced pancytopenia was universal, and hypotension and fluid retention were more common at the higher dose levels. Other toxicity was mild and included nausea, vomiting, diarrhea, and mucositis. No significant hepatic, renal, or cardiac toxicity was seen. We conclude that the dose of HHT 4 mg/m2 for 7 days by continuous infusion in combination with cytarabine is safe for patients with AML; and this combination is appropriate for a phase II evaluation.
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PMID:Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia. 143 3

A 59-year-old man was admitted because of generalized lymphadenopathy with fever and vomiting. His peripheral blood showed leukocytosis with a WBC of 93,500/microliters, and the bone marrow picture revealed a predominance of blast cells. The blasts were negative for peroxidase, alpha-naphthyl butyrate esterase and PAS, and had the phenotype of CD 7, 13 and 33 positive. A diagnosis of AML M0 was made, based on the criteria of the NCI-sponsored workshop in 1988. His initial status had been compromised by acute renal failure which necessitated hemodialysis. He responded partially to chemotherapy consisting of daunorubicin, cytarabine and prednisolone. However leukemia recurred and the patient suffered from various episodes of infection and died six months after admission. The Southern blotting showed the germ line configuration for TCR-beta chain and immunoglobulin heavy chain genes. No messenger RNA was detected for myeloperoxidase, c-myc and c-jun, while c-fms, c-fos and c-myb were expressed on Northern blotting. It is intriguing to detect c-fms and c-fos expression in these poorly differentiated leukemic cells.
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PMID:[A case report of AML M0:CD7, 33 (+) AML M0 case initially presented with cervical lymphadenopathy]. 160 10

Since continuous infusion of daunorubicin and of carboplatin have shown efficacy and reduced toxicity in early phase studies in acute myeloid leukemia (AML), 34 elderly patients with high-risk AML were treated with continuous infusion daunorubicin, 30 mg/m2 per day, from day 1 to day 4, and carboplatin, 200 mg/m2 per day from day 3 to day 7. Seven patients had therapy-related AML and/or AML following a myelodysplastic syndrome at diagnosis, 15 were in first and two in second relapse, and 10 were resistant to previous anthracycline and cytarabine therapy. Nine patients or 26%, with a 95% confidence interval (CI) ranging from 18-67%, achieved complete remission, including one patient at diagnosis (14%, CI: 0-58%), seven with relapsed AML (41%, CI: 18-67%), and one with resistant AML (10%, CI: 0-45%). Median durations of neutropenia below 0.5 x 10(9)/l and of thrombocytopenia below 20 x 10(9)/l were 24 and 20 days respectively. Severe toxicity included infections in 20 patients (59%), bleeding in two (6%), cardiac anomalies in two (6%), and vomiting in one (3%). Overall four patients (12%) died from chemotherapy related toxicity and 21 (62%) had resistant disease. Median overall survival was 4 months and median disease-free survival 8 months. We conclude that this regimen had efficacy with reduced toxicity in relapsed patients. Higher dosages for the same drugs could be tolerated by better risk patients for precise evaluation of cross reactivity with cytarabine-based regimens.
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PMID:Continuous-infusion daunorubicin and carboplatin for high-risk acute myeloid leukemia in the elderly. 164 Jul 28

An efficiency of the acute myeloblastic leukemia therapy has been assessed in 79 patients aged over 60 years. Twenty six patients out of this group have been treated with usual or reduced doses of doxorubicin and cytarabine (ADR-Ara-C) 35--low doses of cytarabine (LD Ara-C), 11-6-mercaptopurine (6 MP), and 7 patients died before chemotherapy. Complete remission in group treated with ADR-Ara-C was achieved in 23% of patients while partial remission in 42%. Median survival in this group was 5.8 months (range from 0.5 to 16 months). Percentage of the complete remissions in the group treated with LD-Ara-C was 6%, and partial remissions 40%. Median survival was 4.7 months (range from 0.5 to 14.2 months). Partial remission in 5 out of 11 patients treated with 6 MP (36%) and no complete remissions were noted. Median survival was 3.9 months. Therapy with ADR-Ara-C produced marked leucopenia and thrombocytopenia in the majority of treated patients. Vomiting, hemorrhagic complications, and bacterial infections have also been noted. These adverse reactions have been less frequent in patients treated with LD-Ara-C, and 6 MP. Ten patients (38%) treated with ADR-Ara-C and 7 patients treated with LD-Ara-C died during remission inducing therapy.
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PMID:[Results of treating acute myeloblastic leukemia in patients over 60 years of age]. 184 11

Thirty two patients with refractory or recurrent acute leukemia or blast crisis of chronic myelocytic leukemia were treated with 1-beta-D-arabinofuranosylcytosine (Ara-C), 100 mg/m2 [group I (n = 15)] or 200 mg/m2 [group II (n = 18)], and tetrahydrouridine (THU) 350 mg/m2, given concurrently as a 3 h continuous intravenous infusion at 12 h interval for eight doses. Two of 13 (15.3%) evaluable patients in group I achieved a complete response, both of whom had acute myelocytic leukemia. In group II, seven of 14 evaluable patients (50%) obtained objective responses--six with complete responses (42.8%) and one with partial response (7%). Myelosuppression was seen in all patients with a median duration of 32.5 days (group I) and 36.3 days (group II), respectively. Non-hematologic toxicity consisted of nausea, vomiting, diarrhea, conjunctivitis, skin rash, hepatocellular toxicity, hemorrhage, and renal toxicity. Pharmacokinetic studies revealed, for group I, mean peak plasma Ara-C levels at 3 h (Cp3h) of 1254 ng/ml, area under the curve (AUC) 4651 ng x h/ml, total body clearance (TBC) 32.65 l/h/m2, renal clearance (RC) 7.04 l/h/m2 with a mean of 12.36% of the injected amount of Ara-C excreted unchanged in urine over the first 24 h. The corresponding mean values for group II are Cp3h 3305 ng/ml, AUC 15080 ng x h/ml, TBC 20.48 l/h/m2, RC 7.02 l/h/m2 and 26.23%. Ara-C 200 mg/m2 combined with THU gave serum Ara-C levels and response rates comparable to those achieved with high dose Ara-C (HiDAC) (greater than or equal to 1 g/m2). Central nervous system toxicity associated with HiDAC was not seen. Pharmacokinetics for uracil arabinoside (Ara-U) in patients treated with Ara-C 200 mg/m2 plus THU, were comparable to values seen with Ara-C for Cp3h, AUC and 24 h urine, amounting to 3160 ng/ml, 21717 ng x h/ml and 23.62% whereas TBC was significantly lower (p less than 0.001) for Ara-U than for Ara-C (3.02 versus 20.48 l/h/m2).
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PMID:Therapy of refractory/relapsed acute leukemia with cytosine arabinoside plus tetrahydrouridine (an inhibitor of cytidine deaminase)--a pilot study. 196 Oct 42

Thirteen patients with leukemia were treated with a combination of cytosine arabinoside (ara-C) (3 g/m2 by 1-h infusion every 12 h for 12 doses) and etoposide (100 mg/m2 daily over 1 h for 3 doses). Toxicity of the regimen consisted of severe hematologic suppression, moderate abdominal colic with vomiting and diarrhea, and occasionally severe central nervous system (CNS) toxicity. Two patients received the regimen as consolidation for acute myelogenous leukemia in remission. Of the remaining 11 patients with chronic myeloid leukemia (CML)-blast crises or relapsed/refractory acute myeloid leukemia (AML), nine patients (82%) obtained CR (or chronic phase) and two patients obtained partial remission (PR). High-dose ara-C and etoposide is an effective but toxic regiment for the treatment of relapsed or refractory myeloid leukemias.
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PMID:High-dose cytosine arabinoside and etoposide in the treatment of relapsed or refractory adult leukemia. 198 40

Intensive sequential chemotherapy with mitoxantrone, 12 mg/m2/d on days 1 through 3, etoposide, 200 mg/m2/d as a continuous infusion on days 8 through 10, and cytarabine, 500 mg/m2/d as a continuous infusion on days 1 through 3 and 8 through 10 was administered to 72 patients aged less than 60 years with previously treated acute myelogenous leukemia (AML). Forty patients had refractory AML (nonresponse to prior therapy, early first relapse, or multiple relapse) and 32 had late first relapse. Sixty-one percent of patients, with a 95% confidence interval (CI) ranging from 49% to 72%, achieved complete remission (CR), including 45% (CI: 30% to 62%) of refractory patients and 81% (CI: 64% to 93%) of late first relapse patients. Twenty-nine percent of patients (CI: 19% to 41%) did not respond to therapy and 10% (CI: 4% to 19%) died from therapy-related toxicity. Median duration of aplasia was 30 days. Nonhematologic WHO grade 3 or more toxicity included sepsis (57% of patients), vomiting (10%), mucositis (35%), diarrhea (7%), skin rash (6%), and hyperbilirubinemia (11%). Postinduction therapy was attempted in 36 of 44 CR patients: 16 of them received a second course of the same regimen, 7 received maintenance chemotherapy, 4 underwent autologous bone marrow transplantation (BMT), and 9 allogeneic BMT. At a median follow-up of 20 months, 23 of the 44 complete remitters have relapsed, 1 to 14 months after achievement of CR, including 19 of 31 patients not undergoing BMT. Median survival is 7 months with 16% (CI: 4% to 28%) projected survival at 47 months. Median disease-free survival is 6 months with 21% (CI: 3% to 39%) of CR patients projected to remain disease-free at 46 months. Twenty-six percent (CI: 13% to 43%) of the evaluable patients who did not receive transplantation had inversion of CR duration. Among patients younger than 50 years, there was no significant difference in disease-free survival between patients receiving postinduction chemotherapy and those receiving BMT. We conclude that this chemotherapy regimen is highly efficient and could be used as first-line therapy in young patients with AML.
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PMID:Intensive sequential chemotherapy with mitoxantrone and continuous infusion etoposide and cytarabine for previously treated acute myelogenous leukemia. 201 32


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