Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Navelbine (NVB) is a new semi-synthetic Vinca alkaloid selected on the basis of its affinity for tubulin. NVB inhibits the polymerisation of tubulin and it has significant antitumor activity on P388 and L1210 leukemias and some other experimental tumors. In the present study, 20 patients (9 carcinomas, 10 lymphomas and 1 blastic crisis of chronic myeloid leukemia) received a median of 4 weekly i.v. doses of NVB. Two patients at least received each dose level: 3.6 mg/m2 (1/10 of the LD10 dose/kg in BDF1 mice), 7.2, 12, 18, 32.4, 35 and 43 mg/m2 per week. A total of 89 doses were administered. All patients had been first heavily pretreated and 17 of them had received a Vinca alkaloid. Leukopenia (neutropenia) was the dose-limiting toxicity. There was no thrombocytopenia. Leukopenia was dose-related and first seen at 32.4 mg/m2 per week. The maximal tolerated dose appears to be about 43 mg/m2. At that dose, 2 out of 3 patients developed severe leukopenia and neutropenia. One localized allergic reaction, one case of transient hepatic dysfunction, and 2 reversible peripheral neuropathies were seen. Pharmacokinetics, studied with a radioimmunoassay (RIA) method, suggested an elimination half-life of 30 h and a plasma clearance of 75 l/h. Four patients with Hodgkin's disease and two patients with non-Hodgkin's lymphoma, all of them refractory to vincristine (VCR) and/or vinblastine (VBL), showed minor responses lasting 2-8 weeks. They had received between 4 and 12 doses of 30 and 43 mg/m2. We recommend for phase 11 trials the dose of 40 mg/m2 per week.
 ...
PMID:Phase I pharmacologic study of a new Vinca alkaloid: navelbine. 401 23

This study examined the ability of the semi-synthetic vinca alkaloid, Vinorelbine/Navelbine, to cause apoptotic death in freshly obtained primary leukaemia cells from 53 patients with haematological malignancies, including 22 patients with acute lymphoblastic leukaemia (ALL), 24 patients with chronic lymphocytic leukaemia (CLL), three patients with chronic myeloid leukaemia in blast crisis (CML-BC) and four patients with acute myeloid leukaemia (AML). Vinorelbine caused apoptosis in primary leukaemia cells from 42 (79%) of these leukaemia patients. Objective responses, including complete remission (CR) and CR with incomplete haematological recovery, were achieved in 12 of 17 (71%) patients with aggressive and therapy-refractory leukaemias, including five of nine patients with relapsed ALL, three of three patients with CML-BC and four of five patients with rapidly progressive CLL, who were treated with a vinorelbine-based salvage chemotherapy regimen. Drug sensitivity profiling of multidrug-resistant primary cancer cells using apoptosis assays revealed a significant association between Vinorelbine sensitivity in vitro and the likelihood of an objective clinical response to Vinorelbine-based chemotherapy. Vinorelbine-sensitivity testing of primary leukaemia cells might help tailor Vinorelbine-based salvage regimens to those patients who are most likely to respond.
 ...
PMID:Vinorelbine-based salvage chemotherapy for therapy-refractory aggressive leukaemias. 1706 78