General Information

Treanda is a rationally designed purine analog and alkylator hybrid. It damages the DNA in cancer cells, which leads to the normal path of cell death (apoptosis). It also stops cancer cells from dividing to create new cancer cells.

Treanda is specifically indicated for: 1) the treatment of chronic lymphocytic leukemia where efficacy relative to first line therapies other than chlorambucil has not been established, and 2) indolent B-cell non-Hodgkin’s lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen.

Mechanism of Action

Treanda contains bendamustine hydrochloride, an alkylating drug. Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups. These groups form covalent bonds with electron-rich nucleophilic moieties, resulting in interstrand DNA crosslinks. The bifunctional covalent linkage can lead to cell death via several pathways. Bendamustine is active against both quiescent and dividing cells. However, the exact mechanism of action of bendamustine remains unknown.

Side Effects

Adverse events associated with the use of Treanda for chronic lymphocytic leukemia may include, but are not limited to, the following:

Pyrexia

Nausea

Vomiting

Asthenia

Fatigue

Malaise

Weakness

Dry mouth

Somnolence

Cough

Constipation

Headache

Mucosal inflammation

Stomatitis

Adverse events associated with the use of Treanda for the treatment of non-Hodgkin's lymphoma may include, but are not limited to, the following:

Nausea

Fatigue

Vomiting

Diarrhea

Pyrexia

Ratigue

Rebrile neutropenia

Pneumonia

Hypokalemia

Dehydration.

Dosing/Administration

Treanda is supplied as a powder in a 100 mg vial to be reconstituted with sterile water for intravenous administration. The recommended initial dose of the drug for the treatment of non-Hodgkin's lymphoma is 120 mg/m2 administered intravenously over 60 minutes on days one and two of a 21-day cycle, up to eight cycles. Treanda administration should be delayed in the event of a Grade 4 hematologic toxicity or clinically significant > Grade 2 non-hematologic toxicity.
Dose modifications for hematologic toxicity: reduce the dose to 90 mg/m2 on days one1 and two of each cycle. If Grade 4 toxicity recurs, reduce the dose to 60 mg/m2 on days one and two of each cycle.
Dose modifications for non-hematologic toxicity: reduce the dose to 90 mg/m2 on days one and two of each cycle. If Grade 3 or greater toxicity recurs, reduce the dose to 60 mg/m2 on days one and two of each cycle.

The recommended initial dose of the drug for the treatment of chronic lymphocytic leukemia is 100 mg/m2 administered intravenously over 30 minutes on days one and two of a 28-day cycle, up to six cycles. Treanda administration should be delayed in the event of Grade 4 hematologic toxicity or clinically significant >Grade 2 non-hematologic toxicity.
Dose modifications for hematologic toxicity: reduce the dose to 50 mg/m2 on days one and two of each cycle; if Grade 3 or greater toxicity recurs, reduce the dose to 25 mg/m2 on days one and two of each cycle.
Dose modifications for non-hematologic toxicity: reduce the dose to 50 mg/m2 on days one and two of each cycle.

Clinical Trial Results

FDA approval for Treanda for the treatment of chronic lymphocytic leukemia was based on the results of an open-label, randomized, controlled multicenter trial in 301 previously-untreated patients with Binet Stage B or C (Rai Stages I - IV) CLL requiring treatment. The subjects received either Treanda at 100 mg/m2, administered intravenously over a period of 30 minutes on days one and two or chlorambucil at 0.8 mg/kg administered orally on days one and 15 of each 28-day cycle. Efficacy endpoints were objective response rate and progression-free survival. The overall response rate was 59 percent in the Treanda arm compared to 26 percent in the chlorambucil arm (p).

FDA approval for Treanda for the treatment of non-Hodgkin's lymphoma was based on the results of a single arm study of 100 subjects with indolent B-cell NHL that had progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. All subjects received Treanda intravenously at a dose of 120 mg/m2, on days one and two of a 21-day treatment cycle. They were treated for up to eight cycles. Overall response rate was seen in 74 of the subjects (64.3 percent). The median duration of response was 9.2 months.