Bi-functional alkylating agent.
A purine analog/alkylator hybrid.
Trade name Treanda.
Induces apoptosis by p53 dependent alkylating activity.
Induces durable DNA damage with rapid cell death via apoptosis and mitotic catastrophe.
Cross links single and double-stranded DNA and is active in both quiescent and dividing cells.
Has more pronounced and long-lasting DNA damaging abilities than other alkylating agents.
Has alkylating properties similar to the nitrogen mustard family, such as cyclophosphamide, chlorambucil and melphalan.
Inhibits DNA, RNA and protein synthesis.
Specifically inhibits the suppression of genes involved in DNA repair and mitotic checkpoints.
Downregulates mitotic checkpoints accounting for its anti tumor activity in resistant and refractory disease.
Contains a nitrogen mustard group to act as an alkylating agent, a purine like benzimidazole ring as a purine analogue and an alkane carboxylic acid allowing water solubility.
Benefits include water solubility, higher potency than other nitrogen mustard agents and less toxicity than other alkylating drugs.
Associated with a low rate of DNA repair associated with DNA damage induced by this agent compared to other alkylating agents.
Has only partial cross resistance with other alkylating agents.
Retains activity in cancer cells that are resistant to conventional alkylating agents.
Induces apoptosis and induces cell death via an alternative mechanism, mitotic catastrophe, which occurs in cells that enter mitosis with significant DNA damage and in cells that lack p53nor capases.
Retained activity even in the absence of a functional apoptotic pathway.
Approved for treatment of CLL and indolent non-Hodgkin’s lymphoma refractory to rituximab.
In phase II/III studies in advanced refractory, relapsed or progressive indolent lymphomas or mantle cell lymphoma had an overall response rate of 73-83% and a complete remission rate of 11-18%.
In untreated patients with indolent B cell lymphoma rituximab and bendamustine is equivalent to R-CHOP.
In a phase III study of Bendamustine plus Rituximab vs R-CHOP in patients with newly diagnosed stage III/IV indolent lymphoma or mantle cell lymphoma: After median of 45 months of followup median progression free survival was 69.5% vs 31.2%.
Associated with myelosuppression, nausea, vomiting, diarrhea and fatigue.
Has an overall response rate in relapsed or refractory aggressive non-Hodgkin’s lymphomas of 44%-56%.
In combination with other anti lymphoma chemotherapy agents or rituximab in indolent lymphomas or mantle cell lymphoma provides high overall and complete response rates.
In a study comparing bendamustine and rituximab with standard R-CHOP therapy in 514 patients with untreated indolent non-Hodgkin’s lymphoma or mantle cell lymphoma: at a median follow-up of 45 months, median progression free survival was 69.5 months in the bendamustine group versus 31.2 months for the R-CHOP group (Rummel MJ et al).
Bendamustine-rituximab should be considered first-line therapy for indolent lymphomas or mantle cell lymphoma.
In a phase II trial of bendamustine 120 mg meter squared on days one and 2 every 3 weeks in patients with rituximab refractory indolent lymphoma the response rate was 82% N. median progression free survival 8.3 months (Friedberg JW et al).
In a phase II study of bendamustine 120 mg meter squared for 6-8 cycles once every 3 weeks overall response rate for follicular lymphoma with 74% (Kahl BS et al).
Phase III trial of 305 patients with untreated CLL treated with 100 mg/m2 IV on days 1 and 2 vs. chlorambucil 0.8 mg/kg orally days 1 and 15, every 28 days for up to 6 cycles: overall response rate 68% in bendamustine group vs 39% in chlorambucil group, with a complete remission rate of 39% vs 2%, respectively (Knauf).
Knauf study progression free survival of bendamustine 21.7 months compared to 9.3 months for chlorambucil, with median duration of remission of 18.9 months vs 6.1 months, respectively.
German CLL study group treatment of pretreated patients noted responses 9 of 16 patients treated with Treanda-recommended doses 70 mg/m2 days 1 and 2 every 4 weeks-median duration of response was 42.7 months, with a median survival for all patients was 45.6 months.