Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0038362 (stomatitis)
 8,852 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

CI-980 is a synthetic mitotic inhibitor that binds to the colchicine binding site of tubulin. It demonstrates broad activity against human and murine tumor models and shows no cross resistance with tumor models whose mechanism of resistance is mediated by P-glycoprotein (MDR-1). A phase I study was completed in 25 patients with solid tumors using a 24-hour infusion schedule, with courses repeated every 3 weeks. Eight dose levels were tested between 1.2 and 15.6 mg/m2. The maximum tolerated dose was 14.4 mg/m2. Neutropenia was dose-related but not dose-limiting; thrombocytopenia was infrequent. CNS toxicities were dose-limiting and consisted of dizziness, headache, loss of coordination, loss of consciousness, nervousness, and other symptoms. These events occurred near the end of the infusion and were reversible, usually within 24 hours. One patient who was to be treated at dose level 8 (intended dose was 19.2 mg/m2; actual dose was 15.6 mg/m2) became encephalopathic prior to completion of the infusion. Other adverse events included gastrointestinal toxicities (nausea, vomiting, anorexia, constipation, stomatitis, dyspepsia, bleeding, cheilitis), IV site erythema, fever, and fatigue. A partial response was observed in one patient with colon cancer and reductions in CA-125 levels were observed in 2 patients with ovarian cancer. Pharmacokinetics were linear and dose-proportional. Results indicate high systemic clearance and wide tissue distribution. Mean pharmacokinetic parameter values: T1/2 = 5.52 hours, plasma clearance 1163 mL/min/m2, and Vdss 376 L/m2.
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PMID:A phase I trial and pharmacokinetic evaluation of CI-980 in patients with advanced solid tumors. 938 46

The potential mechanism of the chemotherapy resistance in acute myeloid leukemia (AML) is the multidrug resistance (MDR-1) gene product P-glycoprotein (P-gp), which is often overexpressed in myeloblasts from acute myeloid leukemia. In a multicenter clinical trial, 38 patients with poor risk forms of AML were treated with tetrandrine (TET), a potent inhibitor of the MDR-1 efflux pump, combined with daunorubicin (DNR), etoposide and cytarabine (TET-DEC). Overall, post-chemotherapy marrow hypoplasia was achieved in 36 patients. Sixteen patients (42%) achieved complete remission or restored chronic phase, 9 achieved partial remission (PR) and 13 failed therapy. Toxicities included infection, myelosuppression, stomatitis, mucositis, cerebellar toxicity and reversible cardiotoxicity. There was no significant difference in response for P-gp-positive and -negative patients. P-gp function was assessed in 26 patients by flow cytometric analysis, TET-contained plasma-augmented DNR accumulation relative to pretreatment plasma in K562/A02 cells by a median value of 88+/-101% (range, 11-501%). However, there was no difference in DNR uptake between responding and non-responding patients. Our data showed that TET-DEC was relatively well tolerated in these patients with poor risk AML, and had encouraging antileukemic effects.
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PMID:Combination of tetrandrine as a potential-reversing agent with daunorubicin, etoposide and cytarabine for the treatment of refractory and relapsed acute myelogenous leukemia. 1621 52