Demcizumab
From Wikipedia, the free encyclopedia
| Monoclonal antibody | |
|---|---|
| Type | ? |
| Target | DLL4 |
| Legal status | |
| Legal status |
|
| Identifiers | |
| CAS Number | |
| DrugBank | |
| ChemSpider |
|
| UNII | |
| KEGG | |
| ChEMBL | |
Demcizumab /dɛmˈsɪzʊmæb/ is a humanized monoclonal antibody which is used to treat patients with pancreatic cancer or non-small cell lung cancer. Demcizumab has completed phase 1 trials and is currently undergoing phase 2 trials. Demcizumab was developed by OncoMed Pharmaceuticals in collaboration with Celgene.[1]
Demcizumab blocks Delta-like ligand 4 (DLL4), a ligand of Notch receptors. Notch signaling has been implicated as a key signaling pathway in cancer stem cells. By treating patients with a combination of Demcizumab and a cytotoxic chemotherapy, it is hoped that a more durable anti-tumor response can be achieved than with chemotherapy alone.[citation needed]
Adverse effects
Demcizumab has been known to cause many adverse effects in patient. The most common side effects are hypertension, fatigue, anemia, and headaches. More adverse effect are nausea, hypoalbuminemia, dizziness, and dyspnea occurred. Finally, some uncommon side effects are heart related illness forming half way through the study.[2]
Phase 1 Trials
The patients that were chosen are older than 21, life expectancy greater than three months, histologically confirmed metastatic, and normal hematologic and clotting parameters. Patients that were excluded received therapy four weeks or earlier, known HIV infection, bleeding disorder, receiving anticoagulants, uncontrolled hypertension, and pregnant or nursing. In addition people that have New York Heart Association Functional Classification II, III, and IV, uncontrolled seizers, active neurological diseases, and significant intercurrent illness are excluded.[2]
Phase 1a trials shows that the drug will be a durable anti-tumor response. In the Phase 1b trials shows the safety and pharmacokinetics that help decide what the maximum tolerated dose is. They dosed fifty-five patients either weekly with a doses ranging from .5 to 5 mg/kg or dosed biweekly with doses ranging from 2.5–10 mg/kg.
The Phase 1 trials show that Demcizumab has a tolerable short term safety profile with common side effects of hypertension and fatigue. The recommended dose is 5 mg/kg until further research have been done.[3][2]