Calcitriol Treatment for mild gastrointestinal toxicities primarily involves the initiation of supportive care

However, no pharmacokinetic analyses were performed and no pharmacokinetic/pharmacodynamic relationship has been established for inhibition of feline Kit with Gleevec. Recently, a cat with systemic mastocytosis was treated with Gleevec at a dose of 10 mg/kg.46 The cat exhibited Imiquimod a complete response to therapy at 5 weeks of treatment with no obvious toxicity. Interestingly, the malignant mast cells possessed a mutation in exon 8 of Kit, likely resulting in constitutive activation of Kit and subsequent promotion of uncontrolled mast cell tumor growth. Another feline tumor type that may benefit from Gleevec is vaccine associated sarcoma. As previously mentioned, VAS cell lines were shown to express PDGFR , and Gleevec was shown to block PDGF induced phosphorylation in these cells.
45 Additionally, Gleevec significantly inhibited the growth of VAS tumors in murine xenografts and reversed the protective effect of PDGF on doxorubicin and carboplatininduced growth inhibition. These studies support the notion that PDGFR may promote the growth and Idarubicin Idamycin survival of VAS in vivo and thus may be an appropriate target for therapeutic intervention using targeted approaches. Clinical Toxicities of Tyrosine Kinase Inhibitors Nearly all anticancer therapeutics exhibit some spectrum of clinical toxicities. In human medicine, various degrees are acceptable given an expectation of benefit from the treatment. In veterinary medicine, quality of life is a significant factor in decision making regarding various therapeutics.
Similar to chemotherapeutics, the TKIs often induce toxicities that target normal tissues, likely because Calcitriol 32222-06-3 of the effects of chronic inhibition of receptors expressed on normal cells that require these pathways for cell survival/proliferation under normal homeostatic conditions. These effects are magnified with multitargeted inhibitors compared with those with a very narrow spectrum of kinase inhibition. Therefore, in many respects, TKIs should be viewed as similar to chemotherapeutics with respect to prevention and management of clinical effects. Both Imatinib CGP-57148B Palladia and Kinavet can induce anorexia, vomiting, diarrhea, and gastrointestinal bleeding in treated patients. 66,68,69 Such clinical toxicities appear to be magnified in the setting of malignant mast cell disease in which circulating levels of histamine are often elevated, potentially exacerbating any drug induced gastric/intestinal ulceration.
Treatment for mild gastrointestinal toxicities primarily involves the initiation of supportive care. Should brain the toxicities be significant, a treatment break is warranted, and an alteration in dose or schedule may be indicated. As with toxicities associated with standard chemotherapeutics, it is important to immediately recognize gastrointestinal toxicities secondary to TKIs so appropriate management can be initiated. In addition to toxicities typical of antineoplastic therapies, both Palladia and Kinavet have the capacity to cause unique side effects. Palladia is known to induce a mild, nonlifethreatening neutropenia in a subset of treated patients. This does not seem to predispose dogs to bacterial infection, and the neutropenia often resolves over time. Additionally, a small proportion of Palladia treated dogs will develop localized muscle cramping.