Treanda™ (Bendamustine) Has Significant Activity for Treatment of NHL

Two recent studies presented at the 47th annual meeting of the American Society of Hematology (ASH) in December 2005 suggest high activity of intravenous Treanda for the treatment of non-Hodgkin’s lymphoma.[1],[2]

Treanda is a bifunctional agent with both alkylator and purine-like activity that is currently in phase II testing in a variety of diseases. One advantage of Treanda is that it is not cross resistant with other alkylating agents. Treanda has been marketed and used clinically in Germany for many years in patients with NHL, chronic lymphocytic leukemia, multiple myeloma, breast cancer and other solid tumors such as lung cancer. One randomized study from Germany found that BMF (bendamustine, methotrexate, and 5FU) was more effective for the initial treatment of metastatic breast cancer than CMF (cyclophosphamide, methotrexate and 5FU).[3]

A previous study carried out in Germany and published in the Journal of Clinical Oncology in May 2005 showed significant activity of Treanda and Rituxan® (Rituximab) for the treatment of relapsed or refractory low-grade NHL or mantle cell lymphoma.[4]

A multicenter U.S. and Canadian trial of Treanda evaluated Treanda in combination with Rituxan in 67 patients with indolent or mantle cell lymphoma who had failed chemotherapy was presented at ASH 2005. Thirty-seven per cent had also failed Rituxan.

The overall response rate was 87% with complete responses observed in 33%. The most frequent complications were related to reversible myelotoxicity.

German researchers have also performed a randomized trial comparing BOP (bendamustine, oncovin and prednisone) to COP (cyclophosphamide, oncovin and prednisone) in a randomized trial involving 164 patients with indolent NHL or mantle cell lymphoma.[5] They reported similar complete remission rates but an improved 5 year survival with BOP (61%) compared to COP (46%). Toxicity was reported as acceptable for both regimens.

The second study presented at ASH 2005 was also performed in 17 sites in the United States and Canada and involved 77 patients with relapsed or refractory NHL. Approximately half the patients had follicular NHL and the remainder had more aggressive histologies. All were treated with single agent Treanda, which resulted in an overall response rate of 74% with a complete response rate of 39%. The median duration of response was 6.6 months with a longer duration for follicular lymphoma and a shorter duration of response for patients with transformed histology. Side effects were predominantly related to myelosuppression.

Comments: These studies suggest that Treanda may replace cyclophosphamide as the primary alkylating agent used to treat NHL and other cancers.

[2] Friedberg JW, Cohen P, Cheson BD, et al. Bendamustine HCL (Treanda) results in high rate of objective response in patients with rituximab-refractory and alkylator-refractory indolent B-cell non-Hodgkin’s lymphoma (NHL): results from a phase II multicenter single-agent study (SDX-105-01). Blood . 2005;106:70a, abstract # 229.

[3] Bendamustine prolongs progression-free survival in metastatic breast cancer (MBC): a phase III prospective, randomized, multicenter trial of bendamustine hydrochloride, methotrexate and 5-fluorouracil (BMF) versus cyclophosphamide, methotrexate and 5-fluorouracil (CMF) as first line treatment of MBC.

[4] Rummel MJ, Al-Batran SE, Kim SZ, et al. Bendamustine plus rituximab is effective and has a favorable toxicity profile in the treatment of mantle cell and low-grade non-Hodgkin’s lymphoma. Journal of Clinical Oncology . 2005;23:3383-3389.

[5] Bendamustine, vincristine and prednisone (BOP) versus cyclophosphamide, vincristine and prednisone (COP) in advanced indolent non-Hodgkin’s lymphoma and mantle cell lymphoma: results of a randomized phase III trial (OSHO#9). Journal of Cancer Research in Clinical Oncology. 2006;132:105-112.