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)

The response rate of advanced gastric cancer to cisplatin monotherapy averages 20% and in colorectal cancer no activity of cisplatin monotherapy has been detected in initial studies. Cytarabine is ineffective in gastric cancer and displays borderline activity in colorectal cancer. In vitro studies on cell lines from human digestive cancers have demonstrated a dose and timing dependent enhancing effect of cytarabine on cisplatin antitumor activity. The aim of the present study was to investigate whether this enhancing activity can also be demonstrated in vivo. We have treated 37 patients with advanced gastrointestinal cancer (21 gastric and 16 colorectal), poorly differentiated G3-G4. The treatment included-Day 1: cytarabine 500 mg/m2 0 h and 12 h, cisplatin 15 mg/m2 6 h and 18 h. Day 2-4:cisplatin 30 mg/m2. Cycles were repeated every 4 weeks. Thirty four patients were evaluable for objective response. The overall response rate was 16.7% (CR 2/18, PR 1/18, SD 5/18, PD 10/18) for patients with gastric cancer and 25% (CR 1/16, PR 3/16, SD 7/16, PD 5/16) for patients with colorectal cancer. Grade 4 anemia (WHO criteria) occurred in 1/37 and thrombocytopenia in 1/37 patients. These patients had previous adjuvant chemotherapy. Vomiting grade 3 occurred in 4/37 and hepatotoxicity grade 3 in 1/37 patients. There were no toxic deaths. Our study did not demonstrate any enhancement of cisplatin activity by high dose cytarabine in advanced gastric cancer. There appears to be an enhancing activity on colorectal cancer although true synergism can not be ruled out since cytarabine has a borderline activity in this type of human cancer.
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PMID:Pilot study of enhancement of cisplatin activity by high dose cytarabine in advanced gastric and colorectal (G3/G4) cancer. 893 44

In order to determine the clinically optimal dose of KRN8602, a new anthracycline derivative, in combination therapy for acute leukemia, we performed a pilot late phase II study in combination with cytarabine (Ara-C) for acute myelogenous leukemia (AML), and with vincristine (VCR) and prednisolone (PSL) for acute lymphocytic leukemia (ALL). KRN8602 was given at a dose of 12 or 15 mg/m2 for 5 consecutive days, Ara-C at a dose of 100 mg/m2 for 7 consecutive days, VCR 1.4 mg/m2 (max. 2.0 mg/body) weekly for 4 weeks, and PSL 40 mg/m2 for principally 28 consecutive days. Of 14 patients with relapsed or refractory leukemia entered in the study, thirteen patients were evaluable for safety and 12 were evaluable for response. In AML, there was 1 partial response (PR) in 4 patients at a dose of 12 mg/m2. Against 1 complete response (CR) and 3 PRs in 4 patients at a dose of 15 mg/m2. In ALL, there was 1 PR in 1 case at a dose of 12 mg/m2, and 1 CR and 2 PR in 3 at a dose of 15 mg/m2. Major toxicities were nausea/vomiting and anorexia, but incidences and grades of toxicities were not dose-dependent, and all toxicities were tolerable and manageable. From these results it is concluded that the optimal dose of KRN8602 is 15 mg/m2 for 5 consecutive days in combination with Ara-C for AML, and with VCR and PSL for ALL.
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PMID:[Pilot late phase II study of KRN8602 (MX2), a novel anthracycline derivative, for acute leukemia--a dose finding study in combination]. 998 4

The majority of hematopoietic malignancies have aberrancies in the retinoblastoma (Rb) pathway. Loss in Rb function is, in most cases, a result of the phosphorylation and inactivation of Rb by the cyclin-dependent kinases (cdks), main regulators of cell cycle progression. Flavopiridol, the first cdk modulator tested in clinical trials, is a flavonoid that inhibits several cdks with evidence of cell cycle block. Other interesting preclinical features are the induction of apoptosis, promotion of differentiation, inhibition of angiogenic processes and modulation of transcriptional events. Initial clinical trials with infusional flavopiridol demonstrated activity in some patients with non-Hodgkin's lymphoma, renal, prostate, colon and gastric carcinomas. Main side-effects were secretory diarrhea and a pro-inflammatory syndrome associated with hypotension. Phase 2 trials with infusional flavopiridol in CLL and mantle cell lymphoma, other schedules and combination with standard chemotherapies are ongoing. The second cdk modulator tested in clinical trials, UCN-01, is a potent protein kinase C inhibitor that inhibits cdk activity in vitro as well. UCN-01 blocks cell cycle progression and promotes apoptosis in hematopoietic models. Moreover, UCN-01 is able to abrogate checkpoints induced by genotoxic stress due to modulation in chk1 kinase. The first clinical trial of UCN-01 demonstrated very prolonged half-life (approximately 600 h), 100 times longer than the half-life observed in preclinical models. This effect is due to high binding affinity of UCN-01 to the human plasma protein alpha-1-acid glycoprotein. Main side-effects in this trial were headaches, nausea/vomiting, hypoxemia and hyperglycemia. Clinical activity was observed in patients with melanoma, non-Hodgkin's lymphoma and leiomyosarcoma. Of interest, a patient with anaplastic large cell lymphoma refractory to high-dose chemotherapy showed no evidence of disease after 3 years of UCN-01 therapy. Trials of infusional UCN-01 in combination with Ara-C or gemcitabine in patients with acute leukemia and CLL, respectively, have commenced. In conclusion, flavopiridol and UCN-01 are cdk modulators that reach biologically active concentrations effective in modulating CDK in vitro, and show encouraging results in early clinical trials in patients with refractory hematopoietic malignancies. Although important questions remain to be answered, these positive experiences will hopefully increase the therapeutic modalities in hematological malignancies.
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PMID:Development of cyclin-dependent kinase modulators as novel therapeutic approaches for hematological malignancies. 1124 75

Twenty-five adult patients with previously untreated acute non-lymphocytic leukemia (ANLL) were treated with mitoxantrone (Mto) 12 mg/m2 daily by 30 minutes intravenous (IV) infusion for 3 days and cytosine arabinoside (Ara-C) 200 mg/m2 daily by continuous infusion for 7 days, as an induction therapy. After complete remission (CR) was observed, they were given two more courses of consolidation therapy which was as Mto 12 mg/m2 daily by 30 minutes IV infusion for one day, and Ara-C 200 mg/m2 daily by 30 minutes IV infusion for 5 days. CR was obtained in 18 of 25 patients (72%). Median remission duration was 294 days and length of survival was 366 days. 11 patients (44%) are still in remission. Myelosupression developed in all patients following induction therapy, but it was not observed after consolidation therapies. Non-hematological side-effects consisted of nausea, vomiting, alopecia, stomatitis, and transient elevation in liver enzymes. Our therapeutic responses are similar to those obtained by others.
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PMID:Mitoxantrone and cytosine arabinoside in previously untreated adult patients with acute non-lymphocytic leukemia. 1465 Dec 26

From 1998 to 2001, 5 consecutive cases of AML/TMDS entered our hospital and achieved complete remission (CR) with continuous drip infusion of low-dose etoposide and low-dose Ara-C combined with mitoxantrone (MEtA regimen). The ages of the 5 patients (4 males and 1 female) ranged 32 to 50 years-old, respectively. WBCs were 1,560-45,150/microl, blasts were 12-62%. Bone marrow aspirates revealed trilineage myelodysplasia with various number of blasts. These patients had an acute onset and no preceding hematologic disorders. They were diagnosed M2/TMDS or M4/TMDS. Continuous drip infusion of etoposide (50 mg/body/day) and Ara-C (30 mg/body/day) were given for 11-14 days and a bolus injection of mitoxantrone (8 mg/m2) was added for 2-3 days. Patient 5 was given additional MIT (6.7 mg/m2 on day 6). All cases achieved CR in 21-24 days after the end of the therapy. Toxicities were nausea, vomiting, stomatitis, alopecia and fever due to infection. All were well tolerable, however. Two patients are alive more than 4 years without relapse. MEtA regimen is available for AML/TMDS.
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PMID:[Five cases of de novo acute myeloid leukemia with trilineage myelodysplasia (AML/TMDS) achieved CR with the continuous drip infusion of low-dose etoposide and low-dose cytosine arabinoside combined with mitoxantrone (MEtA)]. 1527 98

Fludarabine plus cytarabine (Ara-C) and idarubicin (FLAI) is an effective and well-tolerated induction regimen for the treatment of acute myeloid leukaemia (AML). This phase III trial compared the efficacy and toxicity of FLAI versus idarubicin plus Ara-C and etoposide (ICE) in 112 newly diagnosed AML patients <60 years. Fifty-seven patients received FLAI, as the first induction-remission course, and 55 patients received ICE. Post-induction treatment consisted of high-dose Ara-C (HDAC). After HDAC, patients in complete remission (CR) received a second consolidation course (mitoxantrone, etoposide, Ara-C) and autologous stem cell transplantation (auto-SCT) or allogeneic (allo)-SCT, according to the age, disease risk and donor availability. After a single induction course, CR rate was 74% in the FLAI arm and 51% in the ICE arm (P = 0.01), while death during induction was 2% and 9% respectively. Both haematological (P = 0.002) and non-haematological (P = 0.0001) toxicities, especially gastrointestinal (i.e. nausea, vomiting, mucositis and diarrhoea), were significantly lower in FLAI arm. In both arms, relapses were more frequent in patients who were not submitted to allo-SCT. After a median follow-up of 17 months, 30% and 38% of the patients are in continuous CR in FLAI and ICE arm respectively. Our prospective randomised study confirmed the anti-leukaemic effect and the low toxic profile of FLAI as induction treatment for newly diagnosed AML patients.
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PMID:Multicentre phase III trial on fludarabine, cytarabine (Ara-C), and idarubicin versus idarubicin, Ara-C and etoposide for induction treatment of younger, newly diagnosed acute myeloid leukaemia patients. 1648 83

The purpose of the study was to identify the association between chemotherapy-induced nausea/vomiting and changes to the electrogastrogram (EGG) of two children suffering from leukemia. After receiving written consent/assent, the children, both with acute lymphoblastic leukemia (ALL), were recruited. One of the subjects, a ten year-old boy, was given 1.1 gm Cytarabine (intravenous infusion for six hours per day) for three days and Tropisetron 5 mg intravenous infusion for 24 hours. The other subject, an eight year-old girl, received the induction phase of TPOG 93HR chemotherapy, which included Epirubicin, Vincristin, L-asparaginase, and Prednisolone and Tropisetron 5 mg on Day 1. The EGG recordings of both patients were recorded for a total of 42 hours by cutaneous electrogastrography over a seven day period. This included two-hour and four-hour readings taken before and immediately following the administration of chemotherapy each day. The position, movements, and activities of the children while on the EGG were recorded on digital video. Four episodes of nausea and vomiting were detected during this period. Pre- and post-nausea and vomiting during the EGG were analyzed using spectrum analysis after the deletion of motion artifacts. The findings of this study indicated that two episodes of nausea were 5.3-10.3% bradygastria and 2.1-10.3% tachygastria, with 85.8% and 100% normal gastric slow waves detected by EGG during the pre-vomiting period. Tachygastria was present in 3.4% and 12.2% of the post-vomiting period of each episode. The association of artifacts with position, movement, and activities must be considered during data collection.
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PMID:[A pilot study: gastric motility and nausea/vomiting in two leukemia children receiving chemotherapy]. 1647 72

We evaluated efficacy and toxicity profiles of fludarabine, Ara-C, idarubicin, and G-CSF (Ida-FLAG) combination chemotherapy in 56 refractory and/or relapsed acute leukemia patients. Patients were treated with fludarabine phosphate 25 mg/m2/d (d1-5), Ara-C 2 g/m2/d (d1-5), idarubicin 12 mg/m2/d (d1-3), G-CSF was given subcutaneously from sixth day until absolute neutrophil count (ANC) >500/microL. One third of the acute myeloblastic leukemia (AML) and 45% of acute lymphoblastic leukemia (ALL) cases were primary refractory disease. In AML patients, complete remission (CR) was achieved in 15 cases (53.6%). One case showed partial remission (PR) (3.6%) and 12 cases (42.8%) had resistant to this regimen (RD). Grade IV hematologic toxicity occurred in all AML cases. Leukocyte recovery time was 16 days. Nonhematologic complications were mild to moderate nausea, vomiting, and mucositis and could be controlled by routine measures. Stem cell transplantation was performed in 5 patients and all achieved CR, 2 autologous and 3 allogeneic. In ALL patients, CR and PR were obtained in 8 (42.2%) and 2 (10.5%) of 22 cases; disease was resistant to Ida-FLAG in 9 (47.3%) cases. Grade IV hematologic toxicity occurred in all ALL cases. Leukocyte recovery time was 17 days. Nonhematologic toxicity consisted of nausea, vomiting, and mucositis and could be controlled by supportive therapy. Autologous transplantation was performed in 1 patient, but relapse disease occurred after 5 weeks. There was no correlation between response rate and leukemia subtype (AML versus ALL), leukocyte count, age, sex, disease status (de novo versus secondary), and RFS (early versus late relapse) (P > 0.05). Median survival was 16 weeks in all cases (22 weeks in AML versus 13 weeks). At present, only 3 patients are alive and 2 of these are in continuous remission. The rest of the patients died. In conclusion, Ida-FLAG is a good choice in cases with refractory/relapsing acute leukemia for salvage chemotherapy. High efficacy and a low-toxicity profile are preferable properties of this regimen, and this regimen has been found to be useful for cytoreduction, especially in candidates for allo-SCT.
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PMID:IDA-FLAG regimen for the therapy of primary refractory and relapse acute leukemia: a single-center experience. 1698 32

In 1992-1993, synergistic interaction of ribonucleotide reductase inhibitors (fludarabine, cladribine) and cytarabine (Ara-C) increasing Ara-CTP concentration in myeloblasts was proved. Based on these findings and encouraging results of the addition of cladribine to standard daunorubicin+Ara-C induction regimen (DAC) in acute myeloid leukemia (AML), the Polish Adult Leukemia Group (PALG) conducted a pilot study on the administration of cytarabine, daunorubicin, and fludarabine (DAF) as a reinduction treatment of AML to assess tolerance, toxicity, and early outcome. The DAF regimen consisted of daunorubicine 60 mg m(-2) day(-1) iv on days 1-3 and fludarabine 25 mg m(-2) day(-1) iv on days 1-5 given before cytarabine 200 mg m(-2) day(-1) in ci on days 1-7. Thirty-four AML patients with median age 39, 24% relapsed and 76% refractory, were included into the study between September 2003 and August 2004. Achieved response rate in the whole study population was 56%; n = 16 patients with complete remission (CR), and n = 3 patients with partial remission (PR). Fifteen of 16 patients achieved CR after the first course of therapy. Only 9% of total population died before the assessment of remission. All patients developed severe neutropenia. Serious infections were observed in 47% of the cases. Severe thrombocytopenia was observed in 72% of the patients. All patients required substitution of platelet concentrates (median 4), and PRBC (median 5). Severe alopecia, mucositis, vomiting were of low frequency. Liver, kidney, or circulatory failure, diarrhea, or polyneuropathy were not observed. The probability of overall survival (OS) for 1 year for the whole study population (34 patients) and the group of 16 patients in CR was: 44% (95% confidence interval [CI] 36-52%) and 69% (95% CI 55-83%), respectively. The probability of leukemia-free survival (LFS) for 1 year was 38% (95% CI 22-54%). Summarizing, DAF regimen used as the induction therapy in relapsed/refractory AML was well tolerated with acceptable toxicity and early efficacy.
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PMID:Daunorubicin, cytarabine and fludarabine (DAF) for remission induction in relapsed or refractory acute myeloid leukemia. Evaluation of safety, tolerance and early outcome--Polish Adult Leukemia Group (PALG) pilot study. 1807 33

Receptor activated tyrosine kinases such as c-kit, c-fms and PDGFR are known targets of inhibition by imatinib mesylate (Gleevec) and are expressed on AML blasts. Marrow stromal cells and monocytes express KIT ligand, M-CSF and PDGF and are therefore capable of activating survival pathways in these leukemic cells. Given the synergy in vitro between Ara-C and imatinib mesylate on AML cell growth inhibition, we initiated a Phase I study combining CLAG+imatinib mesylate in AML patients. Patients with relapsed, refractory AML or CML myeloid blast crisis were eligible to receive Cladribine 5mg/m(2) days 3-7, Cytarabine 2gm/m(2) days 3-7, G-CSF 300mcg days 2-7, and escalating doses of imatinib mesylate given on days 1-15. The level 1 Gleevec dose was 400mg, while level 2 was 600mg and the level 3 dose 800mg. A total of 16 patients were enrolled, 15 AML and 1 CML myeloid blast crisis. The dose escalation occurred as planned and there was no clear evidence of added toxicity due to imatinib mesylate. One patient with an extensive cardiac history died of cardiac causes on day 1 of therapy however no other deaths occurred within 30 days of starting therapy. One patient had a Grade 3 skin rash at dose level 2. The most common toxicities encountered during induction therapy were nausea, vomiting, rash and diarrhea that were transient and/or reversible. At the 800mg dose 1 patient developed a decline in cardiac ejection fraction on day 20 who later died of sepsis, so this was considered a dose limiting toxicity. Of 16 evaluable patients 11 achieved a hypocellular marrow after initial induction with 1 additional patient achieving a hypocellular marrow following a second course of the same regimen. Four patients (25%) achieved a complete morphologic response with normal cytogenetics, 2 patients (12.5%) achieved a complete morphologic response only and 1 patient had a complete response in the bone marrow but incomplete blood count recovery. The overall response rate was 43.8%. The median overall survival was 175 days (95% CI 16.24-333.76) and the median relapse free survival was 76 days. The addition of imatinib mesylate to CLAG was well tolerated with acceptable toxicities and response rates comparable to other salvage regimens. To assess the efficacy of imatinib mesylate in combination with CLAG, a larger phase II trial is now planned.
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PMID:Phase I study of cladribine, cytarabine (Ara-C), granulocyte colony stimulating factor (G-CSF) (CLAG Regimen) and simultaneous escalating doses of imatinib mesylate (Gleevec) in relapsed/refractory AML. 1857 21


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