生物活性

• 描述Vinorelbine Tartrate is a semi-synthetic vinca alkaloid, and inhibits mitosis through interaction with tubulin and always been used as an anti-mitotic chemotherapy drug. Vinorelbine Tartrate exhibits > 20 fold selectivity over axonal microtubules and inhibit proliferation of multiple human tumor cell lines (IC50 = 1.25 nM in HeLa cells). When blocks metaphase or anaphase transition by suppression of microtubule dynamics, the IC50 value is 3.8 nM. Vinorelbine is involved in underlying processes in human tumors, reversing multi-drug resistance reversal of human lung cancer A549/DDP cells, drug sensitivity to cisplatin and intracellular accumulation of rhodamine-123 was increased while expression of P-glycoprotein (P-gp), multi-drug resistance-associated protein (MRP1) and glutathione-S-transferase II (GST-II) in A549/DDP cells was decreased^[4]. When treated with breast cancer, Vinorelbine alone was equivalent to fluoropyrimidine treatment in RR (p = 0.79) while vinorelbine group gave similar results as other regimens for OS (p = 0.849) and PFS (p = 0.143). The RR of vinorelbine-combined regimens was slightly better than that of the other regimens (OR, 1.17), but the difference was not statistically significant. In neoadjuvant setting, vinorelbine treatment was as active as AC (doxorubicin, cyclophosphamide) or DAC (doxorubicin, cyclophosphamide, docetaxel) regimens with respect to RR (p = 0.76) and pathologic complete response (pCR; p = 0.77), but showed lower occurrence of grade 3/4 adverse effects^[5]. In A phase I/II trial neratinib (240 mg) plus vinorelbine (25 mg/m2) was established as the MTD in phase I (n=12). While In phase II, 79 patients with HER2-positive metastatic breast cancer were treated at the MTD. The most common treatment-related adverse events were diarrhea (96%), neutropenia (54%), and nausea (50%). Three patients discontinued treatment due to diarrhea. No clinically important skin side-effects were observed. The OR rate in assessable phase II patients was 41% (no prior lapatinib) and 8% (prior lapatinib)^[6].
• 作用机制Vinorelbine inhibits microtubule assembly by inducing tubulin aggregation into spirals and paracrystals^[3].

• 动物研究
  剂量	Mice: 1.2 mg/kg[3] (i.v.) Rat: 0.12 mg/kg - 1.2 mg/kg[3] (i.v.)
  给药途径	i.v.

• 临床研究

• NCT号	适应症或疾病	临床期	招募状态	预计完成时间	地点
  NCT02645175	Metastatic Breast Cancer ... more >> Fatigue Collapse <<	Phase 2	Terminated(Business Decision)	December 2018	-
  NCT00055887	Lung Cancer	Phase 3	Withdrawn(Study never started.... more >> No patients were enrolled.) Collapse <<	-	United States, Arizona ... more >> St. Joseph's Hospital and Medical Center Phoenix, Arizona, United States, 85013 United States, Idaho North Idaho Cancer Center Coeur d'Alene, Idaho, United States, 83814 United States, Kentucky Cancer Center at Lexington Clinic Lexington, Kentucky, United States, 40504 United States, Louisiana Willis - Knighton Cancer Center Shreveport, Louisiana, United States, 71103-3951 United States, Maryland St. Agnes Cancer Center Baltimore, Maryland, United States, 21229 Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Baltimore, Maryland, United States, 21231-2410 United States, Washington Providence Everett Medical Center - Pacific Campus Everett, Washington, United States, 98206 United States, West Virginia Schiffler Cancer Center Wheeling, West Virginia, United States, 26003 Belgium Algemeen Ziekenhuis Middelheim Antwerp, Belgium, 2020 Canada, Alberta Tom Baker Cancer Center - Calgary Calgary, Alberta, Canada, T2N 4N2 Cross Cancer Institute Edmonton, Alberta, Canada, T6G 1Z2 Canada, Ontario Cancer Care Ontario-London Regional Cancer Centre London, Ontario, Canada, N6A 4L6 Ottawa Regional Cancer Centre Ottawa, Ontario, Canada, K1H 1C4 Canada, Quebec CHUS-Hopital Fleurimont Fleurimont, Quebec, Canada, J1H 5N4 Maisonneuve-Rosemont Hospital Montreal, Quebec, Canada, H1T 2M4 Hopital Notre- Dame du CHUM Montreal, Quebec, Canada, H2L 4M1 McGill University Montreal, Quebec, Canada, H2W 1S6 Centre Hospitalier Universitaire de Quebec Quebec City, Quebec, Canada, G1R 2J6 Israel Soroka University Medical Center Beer-Sheva, Israel, 84101 Rambam Medical Center Haifa, Israel, 31096 Sheba Medical Center Tel Hashomer, Israel, 52621 Tel-Aviv Sourasky Medical Center Tel-Aviv, Israel, 64239 Collapse <<
  NCT00002823	Lung Cancer	Phase 3	Completed	-	-

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