3月21日，美国食品药品管理局(FDA)顾问委员会以7:4的投票结果，建议对脂质体包裹型长春新碱——Marqibo加速审批，该药用于成人复发难治性Ph阴性急性淋巴细胞性白血病的治疗
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