Glivec Research Today is a free monthly online journal that collates and summarizes the latest research about Glivec, including details on gleevec, imatinib, cancer, treatment, side-effects.

Imatinib mesylate in combination with docetaxel for the treatment of patients with advanced, platinum-resistant ovarian cancer and primary peritoneal carcinomatosis : a Hoosier Oncology Group trial.

Matei D, Emerson RE, Schilder J, Menning N, Baldridge LA, Johnson CS, Breen T, McClean J, Stephens D, Whalen C, Sutton G

Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana.

BACKGROUND.: Ovarian tumors frequently express c-Kit and/or platelet-derived growth factor receptors (PDGFRs). Imatinib mesylate blocks the growth of ovarian cancer cells in vitro and may enhance the activity of chemotherapy. This study was conducted to determine the activity of imatinib in combination with docetaxel in patients with recurrent, platinum-resistant epithelial ovarian cancer (EOC). METHODS.: Eligible patients had recurrent, platinum-resistant, or refractory EOC that expressed PDGFRalpha or c-kit, as determined by immunohistochemistry. Imatinib mesylate at a dose of 600 mg orally once daily was administered continuously with docetaxel at a dose of 30 mg/m(2) given intravenously once weekly in Weeks 1 through 4 of every 6-week cycle. The primary endpoint was objective response rate (ORR) as assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). RESULTS.: Thirty-four patients were screened for PDGFRalpha and c-kit expression to enroll 23 patients between December 2003 and October 2005. Four patients had c-kit-positive/PDGFR-negative tumors, 11 patients had PDGFR-positive/c-kit-negative tumors, and 8 patients had c-kit-positive/PDGFR-positive tumors. The median patient age was 56 years (range, 33-76 years). Patients had received a median of 3 prior treatments. The ORR was 21.7% and included 1 complete and 4 partial responses. An additional 3 patients had stable disease for more than 4months. Expression of PDGFR, c-kit, phosphatase and tensin homolog (PTEN), and phosphorylated protein kinase B (Akt) did not predict response to therapy. The most common adverse events encountered were fatigue (83%), nausea (74%), diarrhea (61%), anorexia (52%), and edema (65%), and the majority of those events were graded as grade 1 or 2. CONCLUSIONS.: The combination imatinib and docetaxel was tolerated in patients with heavily pretreated EOC that expressed c-kit or PDGFRalpha. Few patients had sustained responses or stable disease. Cancer 2008. (c) 2008 American Cancer Society.

Published 11 July 2008 in Cancer.
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Articles on Glivec published 11 July 2008:

Chemical Proteomics-Based Drug Design: Target and Antitarget Fishing with a Catechol-Rhodanine Privileged Scaffold for NAD(P)(H) Binding Proteins.   J Med Chem.

Drugs typically exert their desired and undesired biological effects by virtue of binding interactions with protein target(s) and antitarget(s), respectively. Strategies are therefore needed to efficiently manipulate and monitor cross-target binding profiles (e.g., imatinib and isoniazid) as an integrated part of the drug design process. Herein we present such a strategy, which reverses the target --> lead rational drug design paradigm. Enabling this approach is a catechol-rhodanine ... [Abstract] [Full-text]

Articles on Glivec published 10 July 2008:

Novel V600E BRAF mutations in imatinib-naive and imatinib-resistant gastrointestinal stromal tumors.   Genes Chromosomes Cancer.

BRAF and NRAS are commonly mutated in cancer and represent the most frequent genetic events in malignant melanoma. More recently, a subset of melanomas was shown to overexpress KIT and harbor KIT mutations. Although most gastrointestinal stromal tumors (GISTs) exhibit activating mutations in either KIT or PDGFRA, about 10% of the cases lack mutations in these genes. It is our hypothesis following the melanoma model that mutations in BRAF or NRAS may play a role in wild-type GIST pathogenesis. ... [Abstract] [Full-text]

Kinase domain point mutations in Philadelphia chromosome-positive acute lymphoblastic leukemia emerge after therapy with BCR-ABL kinase inhibitors.   Cancer.

BACKGROUND.: BCR-ABL kinase domain (KD) mutations are detected in approximately 45% of patients with imatinib-resistant chronic myeloid leukemia. Patterns of KD mutations in Philadelphia chromosome (Ph)-positive acute lympho- blastic leukemia (ALL) are less well studied. METHODS.: The authors assessed KD mutations in patients with recurrent Ph-positive ALL after treatments that included 1 or more kinase inhibitors (n = 24 patients) or no prior kinase inhibitor (KI) therapy (n = 12 patients). ... [Abstract] [Full-text]

EVI1 activation in blast crisis CML due to juxtaposition to the rare 17q22 partner region as part of a 4-way variant translocation t(9;22).   BMC Cancer, 8(1): 193.

ABSTRACT: BACKGROUND: Variant translocations t(9;22) occur in 5 to 10% of newly diagnosed CMLs and additional genetic changes are present in 60-80% of patients in blast crisis (BC). Here, we report on a CML patient in blast crisis presenting with a four-way variant t(9;22) rearrangement involving the EVI1 locus. METHODS: Dual-colour Fluorescence In Situ Hybridisation was performed to unravel the different cytogenetic aberrations. Expression levels of EVI1 and BCR/ABL1 were investigated using ... [Abstract] [Full-text]

Articles on Glivec published 9 July 2008:

Imatinib for newly diagnosed patients with chronic myeloid leukemia: incidence of sustained responses in an intention-to-treat analysis.   J Clin Oncol, 26(20): 3358-63.

PURPOSE: Imatinib is remarkably effective in treating newly diagnosed patients with chronic myeloid leukemia (CML) in chronic phase (CP). To date, most of the available data come from a single multicenter study in which some of the patients were censored for diverse reasons. Here, we report our experience in treating patients at a single institution in a setting where all events were recorded. PATIENTS AND METHODS: A total of 204 consecutive adult patients with newly diagnosed CML in CP ... [Abstract] [Full-text]

Advances in the treatment of acute myeloid leukemia: From chromosomal aberrations to biologically targeted therapy.   J Cell Biochem.

We describe several recent advances in our understanding and treatment of acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) including the use of cytogenetics to classify these diseases and to identify therapies that are specific for the abnormalities. Cell lines have provided readily available and very relevant models to understand these diseases. The two clear successes include the use of retinoic acid for acute promyelocytic leukemia and tyrosine kinase inhibitors (e.g., ... [Abstract] [Full-text]

Human AQP5 plays a role in the progression of chronic myelogenous leukemia (CML).   PLoS ONE, 3(7): e2594.

Aquaporins (AQPs) have previously been associated with increased expression in solid tumors. However, its expression in hematologic malignancies including CML has not been described yet. Here, we report the expression of AQP5 in CML cells by RT-PCR and immunohistochemistry. While normal bone marrow biopsy samples (n = 5) showed no expression of AQP5, 32% of CML patient samples (n = 41) demonstrated AQP5 expression. In addition, AQP5 expression level increased with the emergence of imatinib ... [Abstract] [Full-text]

Therapeutic choices in patients with Ph-positive CML living in Mexico in the tyrosine kinase inhibitor era: SCT or TKIs?   Bone Marrow Transplant, 42(1): 23-8.

A total of 72 patients with Ph-positive CML in first chronic phase were followed during a 6-year period in two different institutions in México. Among them, 22 were given a reduced-intensity allogeneic SCT, whereas 50 were given a tyrosine kinase inhibitor (TKI), mainly imatinib mesylate. The 6-year overall survival (OS) after the therapeutic intervention for patients allografted or given a TKI was 77 and 84%, respectively (P, NS); the median OS for both groups has not been reached, being ... [Abstract] [Full-text]

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