marqibo硫酸长春新碱是一种新型的鞘磷脂/胆固醇的脂质体包裹的配方。长春新碱，微管抑制剂，已被批准用于所有，非霍奇金淋巴瘤（NHL）和联合治疗方案中使用的各种成人和儿童的血液学和固体肿瘤恶性肿瘤。
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
Marqibo Granted Accelerated FDA Approval
MARQIBO (vincristine sulfate liposome) injection by Talon Therapeutics Talon Therapeutics announced that Marqibo (vincristine sulfate liposome injection) received accelerated approval from the FDA for the treatment of adult patients with Philadelphia chromosome negative (Ph-) acute lymphoblastic leukemia (ALL) in second or greater relapse or whose disease has progressed following two or more anti-leukemia therapies.
The accelerated approval was based on data for overall response rate. Clinical benefit such as improvement in overall survival has not been verified. Marqibo received orphan drug designation for the treatment of ALL from the FDA and from the European Medicines Agency (EMA). Talon Therapeutics intends to submit a Marketing Authorization Application to the EMA in 2013.
Marqibo is a novel sphingomyelin/cholesterol liposome-encapsulated formulation of vincristine sulfate. Vincristine, a microtubule inhibitor, is approved for ALL, Non-Hodgkin's Lymphoma (NHL) and is used in combination regimens for a variety of adult and pediatric hematologic and solid tumor malignancies.