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)

Oral 6-thioguanine (6-TG) is an S-phase antimetabolite with significant activity against acute leukemia. Preliminary reports of activity of iv 6-TG indicated significant activity against advanced colorectal cancer. We conducted a phase II study of iv 6-TG in 29 patients with advanced measurable colorectal cancer. Only one transient partial response occurred. Toxic effects included mild myelosuppression, nausea, vomiting, and minor ECG changes. We discourage further use of iv 6-TG in the dose and schedule we used to treat advanced colorectal cancer.
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PMID:Phase II trial of iv 6-thioguanine in advanced colorectal carcinoma. 727 27

A phase I trial of diglycoaldehyde (Inox) in children with leukemia established that the maximum tolerated dose of a 5-day schedule was 1.5 g/m2/day. A phase II study was undertaken by the Children's Cancer Study Group to evaluate the efficacy of this dose. Forty-seven children with acute leukemia refractory to conventional forms of therapy were entered in the study: 29 patients with acute lymphocyte leukemia/acute undifferentiated leukemia and 18 with acute nonlymphocytic leukemia. Inox was administered at a dose of 1.5 g/m2 as a 4-6 hour iv infusion daily for 5 days every 14 days. Toxic effects included myelosuppression, proteinuria, nausea, vomiting, diarrhea, local tissue reactions, hypocalcemia, transitory serum amylase elevation, and transitory hypotension. There was one life-threatening episode of drug-related renal toxicity. Of the 27 patients who received a minimum of two courses, partial remissions were observed in two patients with acute nonlymphocytic leukemia. Inox was inactive against advanced acute lymphocytic leukemia.
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PMID:Phase II evaluation of diglycoaldehyde (Inox) in children with acute leukemia: a children's cancer study group report. 742 52

High-dose thymidine (dThd) was given to 12 patients with advanced hematological and solid tumors. The dose schedule used was 75 g/sq m/day, given i.v. continuously for 5 days or more. Myelosuppression, especially leukopenia, was the dose-limiting toxicity. Nonhematological toxicities affected the gastrointestinal tract (nausea, vomiting, anorexia, diarrhea, and indigestion) and the central nervous system (somnolence, headache, visual illusions, and memory impairment). Patients who had received cumulative doses of dThd developed alopecia. Thymine crystals were noted in the urine after refrigeration. Tumor regression (less than partial remission) occurred in one patient with melanoma. Three of four patients with acute leukemia had a fall in peripheral white blood cell counts and blasts but no marrow improvement. Four patients with adenocarcinoma (three colon, one unknown primary) had stable disease. Pharmacokinetic studies revealed that, at a dThd dose of 75 g/sq m/day, millimolar concentrations of dThd and thymine can be achieved in the plasma. The half-life of dThd was approximately 100 min. One-third of the plasma concentrations was measurable in the cerebrospinal fluid. dThd was mainly excreted by the kidneys.
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PMID:Clinical phase I-II and pharmacokinetic study of high-dose thymidine given by continuous intravenous infusion. 747 Oct 98

Thirty adult patients with relapsing or refractory acute leukemia were treated with mitoxantrone 10 mg/m2 daily by 20-min intravenous infusion for 5 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 5 days. Complete remission was obtained in 9 of 15 patients (60%) with acute myeloblastic leukemia (AML), with a mean duration of 6 months (range 2-12 months). Among 15 patients with acute lymphoblastic leukemia (ALL), complete remission was obtained in 5 patients (33.3%), with a mean duration of 2 months. Partial remission was achieved in 2 patients with AML and 1 patient with ALL. Myelosuppression developed in all patients following chemotherapy. Nonhematologic side effects consisted of nausea, vomiting, mild alopecia, stomatitis and transient hepatic dysfunction. No cardiopulmonary toxicity or neurotoxicity was observed. Our therapeutic responses are similar to those obtained with high-dose Ara-C and mitoxantrone but with less toxicity.
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PMID:Mitoxantrone and standard dose cytosine arabinoside therapy in refractory or relapsed acute leukemia. 798 76

A nationwide multi-center cooperative phase II clinical study of irinotecan hydrochloride (CPT-11) was conducted to evaluate its efficacy in intractable malignant lymphoma and acute leukemia. In malignant lymphoma, one course of CPT-11 consisted of intravenous drip infusion at a dose of 40 mg/m2 once daily for 3 consecutive days, performed once a week. In acute leukemia, one course of CPT-11 consisted of intravenous drip infusion at a dose of 15 to 20 mg/m2 a day twice daily for 7 consecutive days (1 cycle), performed every 2 to 4 weeks. Among the 79 patients with malignant lymphoma and 50 patients with acute leukemia enrolled in the study, 66 and 41 patients, respectively, completed treatment. These patients had all undergone chemotherapy prior to treatment. Among the malignant lymphomas, the response rate in non-Hodgkin's lymphoma (NHL), including 9 CRs, was 42% (26/62, 95% CI: 30-54%); of these there was a response rate of 39% (5/13), including 1 CR, in adult T-cell leukemia (ATL) as well. In Hodgkin's disease (HD), on the other hand, there were no cases in which efficacy was demonstrated (0/4). The overall response rate in malignant lymphoma was 39% (26/66), and the response rate even among the recurrent intransigent cases was 42% (16/38). The 50% survival time (MST) in the 74 eligible cases of malignant lymphoma was 153 days. In acute leukemia, on the other hand, partial remission was observed in 2 of 17 cases (12%) of acute lymphocytic leukemia (ALL), but no cases of remission were observed in the 24 patients with acute myelogenous leukemia (AML). The overall remission rate in acute leukemia was 5% (2/41, 95% CI: 1-14%). The principal adverse effects were myelosuppression in malignant lymphoma and gastrointestinal symptoms, including diarrhea, nausea/vomiting, anorexia and abdominal pain, in both malignant lymphoma and acute leukemia, and there was little organ damage to the heart, liver or kidney. Myelosuppression and gastrointestinal adverse effects were severe in some of the patients, so caution is required. Based on the above findings, CPT-11 appears to be efficacious in the treatment of non-Hodgkin's lymphoma.
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PMID:[Late phase II clinical study of irinotecan hydrochloride (CPT-11) in the treatment of malignant lymphoma and acute leukemia. The CPT-11 Research Group for Hematological Malignancies]. 821 Feb 56

The purpose of this study was to define, in a phase I study in leukemia, the maximally tolerated dose (MTD), major toxicities, and possible antitumor activity of Topotecan, a new topoisomerase I (topo I) inhibitor. Topotecan was delivered by a 5-day continuous infusion every 3 to 4 weeks to patients with refractory or relapsed acute leukemia, at doses ranging from 3.5 mg/m2 to 18 mg/m2 per course. Twenty-seven patients were treated, including 17 patients with acute myelogenous or undifferentiated leukemia, 7 with acute lymphocytic leukemia, and 3 with chronic myelogenous leukemia in blastic phase. Severe mucositis was the dose-limiting toxicity occurring in two of five patients treated with Topotecan 11.8 mg/m2 per course; a third patient had prolonged myelosuppression. At the MTD of 10 mg/m2 per course, 1 of 12 patients had severe mucositis and 5 had mild-to-moderate mucositis. Nausea, vomiting, diarrhea, and prolonged myelosuppression were uncommon. Three patients (11%) achieved a complete response, two (7%) had a partial response, and one (4%) had a hematologic improvement. The overall complete plus partial response rate was 19%, and 24% in acute myelogenous or undifferentiated leukemia. A novel in vitro assay that quantifies Topotecan-stabilized topo I-DNA complexes in patient samples was used, which demonstrated heterogeneity in the ability of Topotecan to interact with topo I, the intracellular target of Topotecan. This phase I study defined the MTD of Topotecan to be 10 mg/m2 by continuous infusion over 5 days every 3 to 4 weeks in patients with refractory or relapsed acute leukemia. Severe mucositis was the dose-limiting toxicity. Future studies will define the precise activity of Topotecan in different leukemia subsets, its efficacy in combination with other antileukemic drugs, and correlations between Topotecan-induced topo I-DNA complex formation and individual patient response to Topotecan.
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PMID:Phase I study of Topotecan, a new topoisomerase I inhibitor, in patients with refractory or relapsed acute leukemia. 838 70

We investigated the antiemetic effect, safety and usefulness of granisetron tablet on nausea/vomiting induced by cytosine arabinoside (Ara-C) in the chemotherapy for tumors in the hematopoietic organs. Out of 52 cases with malignant tumors in the hematopoietic organs including acute leukemia, 30 in granisetron group had no antiemetic treatment, were evaluated for the clinical efficacy of granisetron and 22 in control group. Their chemotherapies were combination therapy with Ara-C and daunorubicin (DNR), Ara-C and mitoxantrone (MIT), or Ara-C and etoposide (VP-16). In the trial, the dosage of granisetron tablet was 2 mg once a day, and the drug was given before each chemotherapy for 6 consecutive days. In clinical efficacy the effective rate of granisetron (the percentage of cases in which the trial drug was assessed as "Remarkably effective" or "Effective") was more than 80% on each day of administration. There was no adverse event. As the abnormal laboratory test value, only 1 case tested positive in urine protein, whose causal relation to the trial drug was judged as "Unassessable". Granisetron was judged as "Safe" in 31 out of 32 cases (96.9%). In terms of usefulness, the drug was rated "Extremely useful" or "Useful" in 26 out of 30 cases (86.7%). The above results have shown that granisetron tablet, when administered orally once daily at a dose of 2 mg, has an excellent antiemetic effect, and is a safe and useful drug.
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PMID:[Study on the inhibitory effect of oral granisetron against nausea/vomiting induced by cytosine arabinoside containing chemotherapy for tumors in the hematopoietic organs]. 839 61

The aminothiol, amifostine (Ethyol; U.S. Bioscience, West Conshohocken, PA), is a cytoprotective agent that ameliorates the toxicities of anticancer therapy. In vitro, amifostine promotes the formation and survival of primitive hematopoietic progenitors derived from myelodysplastic bone marrow (BM) specimens. To evaluate the hematological effects of amifostine, 18 patients with myelodysplastic syndrome (MDS) and one or more refractory cytopenias received treatment with amifostine in a Phase I/II study. Four cohorts received intravenous treatment with 100, 200, or 400 mg/m2 amifostine three times a week, or 740 mg/m2 weekly for three consecutive weeks followed by 2 weeks observation. Nonresponding patients received a second course of therapy at the next higher dose level depending upon drug tolerance. Bone marrow (BM) progenitor growth was assessed before treatment and after day 21. Diagnoses included refractory anemia (7), refractory anemia with ringed sideroblasts (5), refractory anemia with excess blasts (RAEB) (4), and RAEB-in transformation (RAEB-t) (2). Single- or multi-lineage hematologic responses occurred in 15 patients (83%) treated with the three-times-a-week dose schedule. Fourteen patients had a 50% or greater increase in absolute neutrophil count with amifostine treatment (range, 426 to 11,348/microL). Platelet count increased in 6 (43%) of 14 patients with thrombocytopenia (absolute increase, 16, 000 to 110,000/microL), and 5 of 15 red blood cell transfusion-dependent patients had a 50% of greater reduction in transfusion needs. Assayable hematopoietic progenitors increased in 13 of 15 evaluable patients; including CFU-GEMM (12), BFU-E (8), and CFU-GM (6). Amifostine doses less than or equal to 200 mg/m2 were well tolerated, whereas grade II nausea, vomiting, and fatigue was limiting at higher doses. Three patients with excess blasts before enrollment experienced an increase in BM blast percentage and two patients had evolution to acute leukemia that persisted after treatment withdrawal. We conclude that amifostine administered at doses </=200 mg/m2 three times a week is well tolerated and has hematologic activity in patients with MDS.
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PMID:Stimulation of hematopoiesis by amifostine in patients with myelodysplastic syndrome. 1153 40

The purpose of this study was to determine the maximally tolerated dose of doxorubicin administered during two cycles of intensive chemotherapy with cyclophosphamide and doxorubicin without stem cell support in patients with advanced cancer and to assess the cumulative cardiac toxicity of the regimen by noninvasive radionuclide imaging and by pre-and postchemotherapy endomyocardial biopsies. Thirty-eight patients (thirty-six with high risk or metastatic breast cancer) were treated in a dose-escalation trial using a fixed dose of i.v. cyclophosphamide (4.2 g/m2) administered over 2 h on day 5 and escalating doses of doxorubicin (50-175 mg/m2) given as a 96-h continuous i.v. infusion on days 1-4, using Filgrastim (granulocyte colony-stimulating factor) for hematological support beginning on day 6. All patients underwent pretreatment, and 28 patients underwent postchemotherapy endomyocardial biopsies. Twenty-nine of 38 patients received two cycles of treatment (median number of days between cycles, 44; range, 34-62). Twenty-one patients had received doxorubicin previously at cumulative dose levels </=150 mg/m2; all patients had pretreatment endomyocardial biopsy scores less than 1. One patient treated at the highest dose level of doxorubicin (175 mg/m2) developed symptoms of mild congestive heart failure following two cycles of chemotherapy. Pre- and posttreatment radionuclide ejection fractions were 65 and 45%, respectively; this patient had a posttreatment endomyocardial biopsy score of 1 (damage to <5% of myocytes). One additional patient at this dose level had an asymptomatic biopsy score of 1, with a decrease in ejection fraction from 62 to 43%; this recovered to 58% 5 months after completion of chemotherapy. Six additional patients treated at lower dose levels had abnormal posttreatment endomyocardial biopsies without abnormal posttreatment ejection fractions. Nine patients received only one cycle of chemotherapy: five patients due to decreased cardiac ejection fraction following cycle 1 (two of these patients had normal endomyocardial biopsies, and two patients had biopsy scores of 1); one patient secondary to tumor progression following cycle one; one patient due to persistently detectable Clostridium difficile toxin in the stool; one patient refused cycle two; and one patient died following cycle one of complications related to sepsis. A single patient experienced a grand mal seizure associated with orthostatic hypotension, which was considered the dose-limiting toxicity. The median duration (over two cycles) of granulocytopenia (absolute granulocyte count <500/microliter) at the maximally tolerated dose level of 150 mg/m2 was 8.5 days (range, 5-13 days), and the median duration of thrombocytopenia (platelets <20,000/microliter) was 2.5 days (range, 0-9 days). The median duration of hospitalization including chemotherapy administration was 23 days (range, 19-36 days). Other toxicities included stomatitis, fever, diarrhea, and emesis. One patient developed acute leukemia 54 months posttreatment. We conclude that two courses of high-dose cyclophosphamide and doxorubicin using granulocyte colony-stimulating factor are feasible and safe with tolerable myocardial toxicity as evidenced by serial endomyocardial biopsies. The dose-limiting toxicity encountered was a grand mal seizure. The recommended Phase II dose is doxorubicin 150 mg/m2 administered as a 96-h infusion on days 1-4, with cyclophosphamide 4. 2 g/m2 on day 5 and G-CSF 5 microgram/kg/day started on day 6 and administered until the total WBC is above 10,000/microliter for three consecutive days.
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PMID:High-dose infusional doxorubicin and cyclophosphamide: a feasibility study of tandem high-dose chemotherapy cycles without stem cell support. 981 32

A multi-center phase II clinical study with high dose cytarabine (NS-075) was conducted in adult patients with relapsed and/or refractory acute leukemia. 2 g/m2 cytarabine was given 12 times by 3-hour intravenous infusion every 12 hrs. 46 patients were registered, and 44 were evaluable: 35 with acute myeloid leukemia (AML) and 9 with acute lymphoblastic leukemia (ALL). There were 28 males and 16 females, with a median age of 37.5 years (range 15-68), including 6 of more than 60 years. Among 35 patients with AML, there were 16 (45.7%) complete and 2 (5.7%) partial remissions. Among 9 patients with ALL, there were 2 (22.2%) complete and 1 (11.1%) partial remissions. The major non-hematologic toxicities were gastrointestinal symptoms such as nausea/vomiting, anorexia and diarrhea, as well as fever, infection, conjunctivitis, alopecia, hepatic and renal dysfunctions. Central nervous system (CNS) toxicity was mild and reversible. Therapy-related death occurred in 5 patients resulting from prolonged pancytopenia, which suggests the necessity of strict countermeasures for infections as well as good patient care. These results indicate that high-dose cytarabine is a promising therapy for treatment of relapsed and/or refractory acute leukemia.
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PMID:[A phase II study with high-dose cytarabine (NS-075) in adult patients with relapsed and refractory acute leukemia]. 988 Oct 80


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