FDA于2012年8月9日Marqibo（硫酸长春新碱脂质体注射液）获准用于治疗白血病患者复发2次以上或病情恶化的患者，或在经过2种以上抗白血病药物治疗方案后病情仍有进展的患者。该药主要成分为常用抗肿瘤药长春新碱，由一种类似细胞膜成分的脂质体包裹，每周注射一次，是由南加州旧金山市的Talon Therapeutics公司生产的。
MARQIBO
Pharmacological Class:
Vinca alkaloid.
Active Ingredient(s):
Vincristine sulfate liposome injection; after preparation, each vial contains 0.16mg/mL; for IV infusion.
Company
Talon Therapeutics, Inc.
Indication(s):
Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or has progressed following ≥2 anti-leukemia therapies.
Pharmacology:
Marqibo is a sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate. Non-liposomal vincristine sulfate binds to tubulin, altering the polymerization equilibrium, resulting in altered microtubule structure and function. Non-liposomal vincristine sulfate stabilizes the spindle apparatus, preventing chromosome segregation, triggering metaphase arrest and inhibition of mitosis.
Clinical Trials:
Marqibo was studied in an international, open-label, multi-center, single-arm trial (Study 1). Patients were ≥18 years with Ph- ALL in second or greater relapse or whose disease had progressed after ≥2 treatment lines of anti-leukemia therapy. Patients had to have achieved a complete remission to at least one prior anti-leukemia chemotherapy, defined by a leukemia-free interval of ≥90 days. Patients received intravenous Marqibo monotherapy at 2.25mg/m2 over 60 minutes every 7 days. Concomitant corticosteroids were not permitted beyond Day 5.
The treated population included 65 patients who received at least 1 dose of Marqibo. All of the treated patients had received prior vincristine sulfate and 80% had evidence of residual neuropathy at study baseline. Results demonstrated that among the 65 treated patients, 3 patients (4.6%) achieved complete remission and 7 patients (10.8%) achieved complete remission with incomplete blood count recovery. In these 10 patients, median duration of documented remission was 28 days (95% CI: 7, 36). The median time to the first event of relapse, death, or next therapy was 56 days (95% CI: 9. 65).
Legal Classification:
Rx
Adults:
2.25mg/m2 IV over 1 hour once every 7 days. Dose modifications for peripheral neuropathy: see full labeling.
Children:
Not established.
Contraindication(s):
Demyelinating conditions, including Charcot-Marie-Tooth syndrome. Intrathecal administration (death has occurred).
Warnings/Precautions:
For IV use only; fatal if given by other routes. Discontinue and treat if extravasation is suspected. Preexisting neuromuscular disorders. Monitor for symptoms of neuropathy before and during therapy; if occurs or worsens, delay, reduce or discontinue dose. Monitor CBCs prior to each dose; if Grade 3 or 4 myelosuppression develops, consider dose modification or reduction. Monitor for tumor lysis syndrome; manage if occurs. Institute a prophylactic bowel regimen to mitigate potential constipation, bowel obstruction, and/or paralytic ileus; consider dietary fiber intake, hydration, stool softeners. Monitor liver function tests; if hepatotoxicity occurs, reduce or interrupt dosing. Elderly. Pregnancy (Cat. D); avoid. Nursing mothers: not recommended.
Interaction(s)
Drugs known to interact with non-liposomal vincristine sulfate (eg, phenytoin: increased seizure risk). Avoid concomitant strong CYP3A inhibitors (eg, ketoconazole, itraconazole, voriconazole, posaconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin) or strong CYP3A4 inducers (eg, dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital, St. John’s Wort). Avoid concomitant potent P-gp inhibitors or inducers.
Adverse Reaction(s)
Constipation, nausea, pyrexia, fatigue (may be severe; adjust dose or discontinue), peripheral neuropathy, febrile neutropenia, diarrhea, anemia, decreased appetite, insomnia.
How Supplied:
Kit—1, 3 (vials + supplies)
LAST UPDATED:
4/1/2013
