Gan to kagaku ryoho. Cancer & chemotherapy
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Gan To Kagaku Ryoho · Jul 2009
Review[Small-molecule inhibitors against KIT and PDGFRs especially in GISTs].
Gastrointestinal stromal tumors (GISTs) are one of the representative diseases for which we now use small-molecule inhibitors against KIT and PDGFRs. Most GISTs have gain-of-function mutations of the c-kit or PDGFRA gene. The mutations result in constitutive receptor activation, and the activated receptor stimulates downstream signaling pathways. ⋯ Although molecular target therapy has been very effective, secondary resistance to imatinib often develops during long-term imatinib administration. Secondary mutations of the c-kit gene in addition to primary c-kit gene mutation are a major cause of secondary resistance to imatinib. Now, we can use sunitinib for patients with imatinib-resistant GIST.
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Gastrointestinal stromal tumor (GIST) is the most frequent mesenchymal neoplasm of the gastrointestinal tract. Now, there is widespread scientific and clinical interest in GIST because of identifying in principal pathogenetic defects and development of a specific molecular inhibitor of GIST. GISTs have a gain-of-function mutation in the c-kit protooncogene. ⋯ Imatinib (gleevec) is an oral agent that selectively inhibits c-Kit, whose efficacy proves that a specific inhibitor can counteract the effects of a genetic defect responsible for cancer. Although STI571 was first applied to GIST, it has already revolutionized the treatment of patients with metastases. Now so many molecular target agents are under development in clinical trials.
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Trastuzumab is a recombinant humanized monoclonal antibody directed against HER2. Several issues about its optimal use,mechanism of action or resistance still await convincing answers. Results of large-scale randomized trials and preclinical study might answer these questions. This review summarizes current knowledge about trastuzumab treatment.
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The definition of the TNM classification and staging system of malignant melanoma have been fundamentally revised. Moreover, several clinical guidelines for the management of this neoplasm were recently proposed. ⋯ The significance of high-dose interferon-alpha as adjuvant therapy is still controversial. No effective chemotherapy or biotherapy has been established to date, however, interesting new findings were recently reported in the fields of immunotherapy and molecular targeting therapy.
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Capecitabine, an oral fluoropyrimidine carbamate, is adopted worldwide. As the treatment for metastatic colorectal cancer, capecitabine showed at least comparable efficacy with a favorable safety profile to bolus 5-FU/LV. In a large phase III trial (Xeloda Adjuvant Chemotherapy Trial: X-ACT), as the adjuvant treatment of patients with resected stage III colon cancer, capecitabine showed at least comparable disease-free survival, overall survival, and relapse-free survival with a favorable safety profile to bolus 5-FU/LV. ⋯ The median time to disease progression was 169 days and the median overall survival was 617 days. Hand-foot syndrome (HFS), a characteristic adverse event of capecitabine, was observed in 73.3% of the patients, but the grade 3/4 was observed in 13.3% of the patients and only one patient discontinued the treatment due to HFS. An immediate approval of capecitabine in Japan is expected.