Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027497 (nausea)
 23,468 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In a phase I study conducted by the EORTC Soft Tissue and Bone Sarcoma Group, 40 patients with advanced soft tissue sarcomas, most of whom had gastrointestinal stromal tumors (GISTs), received imatinib at doses of 400 mg q.d., 300 mg b.i.d., 400 mg b.i.d., or 500 mg b.i.d. Dose-limiting toxicities, including severe nausea, vomiting, edema and rash, were seen at the highest dose level; the maximum tolerated dose was therefore 400 mg b.i.d. Imatinib was active in the group of 35 patients with GISTs, producing partial responses in 19 (54%) patients and stable disease in 13 patients (37%). Responding patients have now been followed for a minimum of 10 months. The most common side effects seen in patients continuing on therapy have been periorbital edema (40%), peripheral edema (37.5%), fatigue (30%), skin rash (30%) and nausea/vomiting (25%). Severe late myelosuppression has also been seen occasionally. Eighteen (51%) GIST patients continue to have partial responses and 11 (31%) continue with stable disease. Thus, 82% of patients with GISTs are still obtaining clinically important benefits with continued imatinib therapy. Some patients showed accelerated progressive disease shortly after starting imatinib. On the other hand, following drug withdrawal, 2 patients had reductions in tumor burden and remain alive without drug therapy. In summary, imatinib is generally well tolerated and has significant activity during long-term treatment of patients with advanced GISTs.
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PMID:Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumors: a report of the EORTC Soft Tissue and Bone Sarcoma Group. 1252 78

Imatinib (Gleevec) (formerly STI571) has demonstrated high levels of efficacy in chronic myelogenous leukemia (CML) and gastrointestinal stromal tumors (GIST) and has been used in more than 12,000 patients participating in clinical trials. Experience from clinical trials with imatinib has largely demonstrated the drug to be well tolerated in humans. Common side effects, usually manageable, include nausea, rash, superficial edema, myelosuppression, muscle cramps, and elevated liver transaminases. With longer follow-up and with further experience with the treatment of patients outside of clinical trials, we are able to report on rarer toxicities, the identification of certain predictors of common toxicities, and the clinical experience with male fertility and pregnancy outcomes.
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PMID:Imatinib treatment: specific issues related to safety, fertility, and pregnancy. 1278 71

The aim of this study was to assess the antitumour response and time to progression (TTP) of patients treated with imatinib mesylate (Glivec, Gleevec, formerly STI-571) who had advanced and/or metastatic gastrointestinal stroma tumours (GIST) or other soft tissue sarcomas (STS). Patients with measurable lesions and adequate organ function were entered. They were treated with imatinib mesylate at the dose of 400 mg twice daily (bid). All tumours were subject to a stringent pathological review by an expert panel. Immunohistochemical expression of KIT expression was evaluated. A total of 51 patients (27 GIST, 24 other STS), median age 53 years, median World Health Organization (WHO) performance score 1, were entered. 71% of the patients had received prior chemotherapy. The most frequent side-effects were anaemia (92%), periorbital oedema (84%), skin rash (69%), fatigue (76%), nausea (57%), granulocytopenia (47%) and diarrhoea (47%). Most of these side-effects were mild to moderate and no patient was taken off study due to side-effects. Skin rash and periorbital oedema frequently seem to be self limiting, despite continued treatment. In GIST patients, the current response rates (RRs) are 4% complete remission (CR), 67% partial remission (PR), 18% stable disease (SD) and 11% progression (PD). 73% of GIST patients are free from progression at 1 year. In the other STS group, there were no objective responses. The median time to progression in this subgroup was only 58 days. Imatinib mesylate is well tolerated at a dose of 400 mg bid. This dose is active in patients with KIT-positive GIST, but patients with other STS subtypes unselected for a molecular target are unlikely to benefit.
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PMID:Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. 1534 73

Philadelphia chromosome positive chronic myeloid leukemia (Ph+ CML), in advanced stage of disease, is resistant to standard chemotherapy. Imatinib was found to be effective in these patients. This paper shows our preliminary results. Imatinib mesylate was given to 15 patients during a 9-month period. Nine of them were in accelerated phase and 6 in blastic crisis of Ph+ CML. Patients were evaluated for hematologic and cytogenetic responses. Imatinib mesylate induced complete haematologic response in 12 patients (80% and cytogenetic response in 8 patients (53%). Six patients (40%) had a major cytogenetic response. After a 9-month follow up Ph+ CML progressed in 9 patients (60%) and 4 of them died. The most frequent adverse effects were edema, nausea, neutropenia and thrombocytopenia. Imatinib mesylate has a substantial, but short term activity in the accelerated phase and blastic crisis of the Ph+ CML.
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PMID:[Treatment of chronic myeloid leukemia with imatinib in the accelerated stage of the disease]. 1469 90

Imatinib related non-haematological side-effects are reported in <10% of chronic myeloid leukaemia patients and include oedema, weight gain, nausea, vomiting and muscle cramps. Cutaneous reactions are well-recognized events occurring mostly in patients treated at doses of 600 mg/d and higher, either in stable or progressive disease. We report on our experience relating to dermatological toxicities in imatinib treated CML patients showing a spectrum of skin reactions ranging from rashes to cutaneous carcinoma.
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PMID:Early and tardive skin adverse events in chronic myeloid leukaemia patients treated with imatinib. 1565 2

The prognosis for advanced gastrointestinal stromal tumor (GIST) is poor. However, recent reports from Europe have described the effects of imatinib against metastatic GIST. We herein report the case of a Japanese patient treated with imatinib for advanced GIST. Imatinib at 400 mg daily was given to an adult with multiple liver and peritoneal metastases 17 months after undergoing a GIST resection. The sum of the diameter of all target lesions decreased from 37.7 to 10.9 cm at 6 months. Tinnitus (grade 2), which has not been reported elsewhere as an adverse effect, developed at 2 months. However, it did not require any treatment. Other adverse effects, nausea (grade 2) and anemia (grade 2), resolved spontaneously. Our results are consistent with previous reports that show imatinib to be effective for the treatment of metastatic GIST, and also suggest that imatinib at 400 mg daily for more than 7 months is well tolerated in Japanese adults.
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PMID:Effect of imatinib (STI571) on metastatic gastrointestinal stromal tumors: report of a case. 1567

Twenty-five patients with histologically proven malignant mesothelioma participated in a trial of imatinib mesylate (Glivec) with a starting dose of 400 mg per day taken orally, up to a maximal dose of 800 mg. No responses were observed in the patient group, while three patients showed prolonged (>6 months) stabilization of disease. The median survival time was 398 days (range 88-840); the median time to progression was 63 days (range 29-275). Side effects of the medication were mild and included edema, nausea, constipation and diarrhea. We conclude that further investigation with monotherapy imatinib in mesothelioma is not warranted.
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PMID:Limited efficacy of imatinib mesylate in malignant mesothelioma: a phase II trial. 1595 Oct 53

Fourteen patients with metastatic renal cell carcinoma (RCC) were treated on a Phase II trial with imatinib. Eligible patients had histologically confirmed RCC, metastatic and measurable disease by Response Evaluation Criteria in Solid Tumors (RECIST), Karnofsky performance status (KPS) of at least 70%, life expectancy of more than 3 months, and adequate hematological, renal, and liver function. Imatinib was given orally at a dose of 400 mg bid. The most common toxicities were Grade II/III nausea (28%) and Grade II renal insufficiency (14%). All patients had tumor tested by immunohistochemistry (IHC) for KIT protein (CD117, DAKO). One tumor (7%) demonstrated strong, diffuse expression and the rest were negative. No complete or partial responses were observed in 12 evaluable patients treated with imatinib.
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PMID:Phase II trial of imatinib (Gleevec) in patients with metastatic renal cell carcinoma. 1638 Aug 35

Imatinib (STI571, Gleevec/Glivec) and other small-molecule tyrosine kinase inhibitors are highly effective in the treatment of chronic myeloid leukemia (CML), gastrointestinal stromal tumors and, for example, eosinophilia-associated chronic myeloproliferative disorders. This molecularly targeted approach disrupts abnormal tyrosine kinase dependent signalling pathways, thus providing a preferred treatment option for selected neoplastic disorders with activating mutations of Abelson-, Abl-related-, Kit-, and platelet-derived growth factor receptor A and B genes. Loss of response to imatinib may be due to an acquired resistance of emerging mutant tumor cell clones. Therapy is generally well tolerated. However, toxicities including edema, skin rashes, fatigue, nausea and myelosuppression have been reported. Philadelphia/Bcr-Abl-negative clonal chromosomal abnormalities may develop. Bone marrow trephines obtained from CML patients in complete remission with prolonged pancytopenia secondary to imatinib generally show marrow hypoplasia. Morphological features may be in keeping with either aplastic anemia or myelodysplasia developing in Philadelphia-negative hematopoiesis. Single or multilineage myelodysplasia may be accompanied by an excess of blasts and rarely evolves into acute leukemia in CML patients. Severe adverse hematological effects of imatinib are extremely rare. Current questions involve the molecular mechanisms of hematological side effects of tyrosine kinase inhibitors with special regard to the emergence of distinct aberrant clones.
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PMID:[Hematological side effects of tyrosine kinase inhibition using imatinib]. 1642 5

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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