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)

Chronic myeloid leukemia is a myeloproliferative disorder characterized by the presence of the Philadelphia chromosome, t(9:22). Extramedullary blast crisis is a rare event. Imatinib mesylate has become the treatment of choice, especially for patients for whom allogenic stem cell transplantation is not an option. Imatinib produces complete cytogenetic responses in excess of 80%. However, the penetration of the drug and its metabolites into the CNS (Central Nervous System) is poor. Hence for patients who are on prolonged imatinib therapy and continue to have complete cytogenetic responses, the central nervous system may become a sanctuary site. We report a patient who had a complete hematologic and cytogenetic response and presented with headache and vomiting. The MRI showed meningeal enhancement and the CSF (Cerebro Spinal Fluid) examination was positive for blasts. He was started on cranial radiotherapy and triple intrathecal chemotherapy. He showed good symptomatic improvement and cleared the blasts in the CSF. At the end of radiation, he was in complete hematological remission but had 50% marrow metaphases positive for Philadelphia chromosome. As he did not have a matched sibling donor, the dose of imatinib was increased to 600 mg daily. He continues to be in complete hematologic remission at the time of this report.
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PMID:Isolated central nervous system blast crisis in chronic myeloid leukemia. 1599 75

We report a rare case of symptomatic hypoglycemia in a patient with intra-abdominal recurrence of a previously resected gastrointestinal stromal tumor (GIST). The patient is a 65-year-old woman who underwent resection of a large abdominal mass arising from the stomach, histologically diagnosed as a high-grade leiomyosarcoma. She was lost to follow up. Five years later, the mass recurred; core biopsy demonstrated a CD 117-positive, spindle-cell tumor, consistent with a GIST. She was placed on Gleevec, as there was evidence of multifocal disease, but imaging revealed only mild improvement. Subsequently, her clinical status deteriorated, and she was hospitalized for dehydration, vomiting, and mental status changes. Her blood glucose on admission was 22 mg/dL, and a dextrose infusion (50%) was necessary to maintain adequate blood glucose levels. Measurements of insulin, proinsulin, c-peptide, beta-hydroxybutyrate, and thyroid-stimulating hormone were normal, as were cosyntropin stimulation and glucagon response tests. Suspicions arose for tumor-secreted insulin-like factor. She underwent resection of the dominant 44-cm recurrence, with immediate rebound hyperglycemia, followed by complete normalization of her blood glucose levels. She was discharged on postoperative Day 5 without symptoms or insulin, and is alive with disease at 20 months. Paraneoplastic syndromes occur in only 15 per cent of patients with known malignancies (e.g., lung cancer and metastatic carcinoid), and are rarely reported in the setting of GIST. Hypoglycemia is most often observed in presence of insulinoma and only isolated case reports in GIST patients exist. Overexpression of insulin-like growth factor II is thought to be the mechanism of action. Supportive management and palliative resection or debulking is recommended when possible.
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PMID:Hypoglycemia in the setting of advanced gastrointestinal stromal tumor. 1721 25

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

On December 19, 2008, the U.S. Food and Drug Administration approved imatinib mesylate tablets for oral use (Gleevec(R); Novartis Pharmaceuticals Corporation, East Hanover, NJ) for the adjuvant treatment of adult patients following complete gross resection of Kit(+) (CD117(+)) gastrointestinal stromal tumor (GIST). A randomized, double-blind, placebo-controlled study enrolling 713 patients was submitted. The primary objective of the clinical trial was to compare the recurrence-free survival (RFS) intervals of the two groups. Overall survival (OS) was a secondary endpoint. Eligible patients were > or =18 years of age with a histological diagnosis of GIST (Kit(+)), resected tumor size > or =3 cm, and a complete gross resection within 14-70 days prior to registration. Imatinib, 400 mg orally, was administered once daily for 1 year. The study was terminated after completion of the third protocol-specified interim analysis. At that time, 100 RFS events were confirmed by a blinded central independent review. With a median follow-up of 14 months, 30 RFS events were observed in the imatinib group and 70 were observed in the placebo group (hazard ratio, 0.398; 95% confidence interval, 0.259-0.610; two-sided p-value < .0001). OS results are immature. Most patients in both groups experienced at least one adverse reaction, and 31% of the imatinib group and 18% of the placebo group experienced grade > or =3 adverse reactions. The most frequently reported adverse reactions (> or =20%) were diarrhea, fatigue, nausea, edema, decreased hemoglobin, rash, vomiting, and abdominal pain. Drug was discontinued for adverse reactions in 17% and 3% of the imatinib and placebo-treated patients, respectively.
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PMID:Approval summary: imatinib mesylate in the adjuvant treatment of malignant gastrointestinal stromal tumors. 2020 41

Imatinib mesylate is a widely used tyrosine-kinase inhibitor (TKI) in chronic myeloid leukemia (CML) treatment. Imatinib has contributed to complete and prolong cytogenetic responses so that it is now the standard treatment of CML. Recently, Imatinib mesylate has shown a significantly prolonged progression-free survival and overall survival in metastatic and locally advanced c-Kit positive gastro-intestinal stromal tumors (GISTs) and more recently a prolonged disease-free survival in operated high risk GIST. Imatinib is a welltolerated treatment with few side effects mainly gastro-intestinal symptoms (nausea, vomiting and diarrhea), headaches, rash and periorbital edema. Hemorrhage incidents are rare in patients treated with Imatinib. They are more frequently seen in CML patients. Hemorrhage incidents in CML include in many cases upper gastro-intestinal (GI) tract bleeding and central nervous system bleeding in rare ones. In GIST patients treated with Imatinib, hemorrhage incidents are exclusively made of upper GI tract bleeding consecutive to tumor perforation or necrosis. In our observation, we present the case of a subdural hematoma occurring in a patient treated with adjuvant Imatinib for a high risk localized gastric GIST. No other case of subdural hematoma in GIST treated with Imatinib has been reported in literature.
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PMID:Subdural hematoma during therapy of gastro-intestinal stromal tumor (GIST) with Imatinib mesylate. 2568 60

Imatinib mesylate (IM) represents the first-line treatment of patients with chronic myeloid leukemia (CLM) or gastrointestinal stromal tumor (GIST). It presents several side effects. However, less than 10% are nonhematologic including nausea, vomiting, diarrhea, muscle cramps, and cutaneous reactions. The aim of our study was to identify data regarding IM cutaneous adverse effects (AEs) to improve the clinical diagnosis and management of the more frequent side effects. Skin examination should be done before and during IM treatment so that AEs can be diagnosed and treated early with less impact on chemotherapy treatments and on the quality of life of the patient.
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PMID:Skin lesions in patients treated with imatinib mesylate: a 5-year prospective study. 2741 91