Company:

Cephalon

Alkylating agent

Bendamustine HCl 100mg/vial; lyophilized pwd for IV infusion after reconstitution and dilution; contains mannitol; preservative-free.

Chronic lymphocytic leukemia (CLL).

Bendamustine is a bi-functional mechlorethamine derivative. Mechlorethamine and its derivatives dissociate into electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties. The bifunctional covalent linkage can lead to cell death via several pathways. The exact mechanism of action of bendamustine remains unknown. Bendamustine is active against both quiescent and dividing cells.

In vitro data indicate that bendamustine is primarily metabolized via hydrolysis to metabolites with low cytotoxic activity.

The safety and efficacy of bendamustine were evaluated in an open-label, randomized, controlled multicenter trial comparing bendamustine to chlorambucil. The trial was conducted in 301 previously-untreated patients with Binet Stage B or C (Rai Stages I-IV) CLL requiring treatment. Patients were randomized to receive either bendamustine 100mg/m2 IV on Days 1 and 2 or chlorambucil 0.8mg/kg orally on Days 1 and 15 of each 28-day cycle. Efficacy endpoints of objective response rate and progression-free survival were calculated using a pre-specified algorithm based on NCI working group criteria for CLL. The results of this study demonstrated a significantly higher rate of overall response (59% vs. 26%) and a significantly longer progression-free survival (18 months vs 6 months) for bendamustine compared to chlorambucil.

Give by IV infusion over 30 minutes. 100mg/m² on Days 1 and 2 of a 28-day cycle, up to 6 cycles. May give allopurinol prophylactically for those at high risk of tumor lysis syndrome. Delay treatment for Grade 4 hematologic toxicity or clinically significant ≥Grade 2 non-hematologic toxicity. Hematologic toxicity (≥Grade 3): reduce dose to 50mg/m² on Days 1 and 2 of each cycle; if toxicity recurs, reduce dose to 25mg/m² on Days 1 and 2. Non-hematologic toxicity (clinically significant ≥Grade 3): reduce dose to 50mg/m² on Days 1 and 2 of each cycle. Subsequent cycles: may consider dose re-escalation. Severe renal impairment (CrCl <40mL/min) or moderate to severe hepatic impairment: not recommended.

Not recommended.

Myelosuppression; monitor leukocytes, platelets, hemoglobin, neutrophils closely; restart treatment based on ANC and platelet count recovery. Renal or hepatic impairment. Monitor for infection, infusion reactions, tumor lysis syndrome. Pregnancy (Cat.D); avoid use. Nursing mothers: not recommended.

May be potentiated or antagonized by CYP1A2 inhibitors, inducers.

Neutropenia, pyrexia, thrombocytopenia, nausea, anemia, leukopenia, vomiting, asthenia, fatigue, malaise, dry mouth, somnolence, cough, constipation, headache, mucosal inflammation, stomatitis, increased bilirubin, increased AST or ALT; infection, infusion reactions (discontinue if severe), tumor lysis syndrome, skin reactions (if severe or progressive, withhold dose or discontinue).

Single-use vial—1

5/15/08