Bendamustine as salvage treatment in patients with advanced progressive breast cancer: a phase II study

Abstract

A phase II pilot study of bendamustine as salvage treatment in patients with advanced breast cancer was performed to determine the objective response rates and make further observations on the toxicity of this drug. A group of 37 patients, pretreated with chemotherapy for advanced disease, entered the trial. Treatment consisted of 150 mg/m2 bendamustine on days 1 and 2 of a 4-week treatment course. Patients continued to receive treatment until complete remission and then two further courses, until tumour progression or unacceptable toxicity ensued. A total of 36 patients received at least one treatment course and were assessable for toxicity; 33 patients were evaluable for treatment results. Dose-limiting grade 3 and 4 WHO toxicity occurred in 5 and 3 patients respectively; 27% of patients entered complete or partial tumour remission. The median time to tumour progression was 2 months with a range of 1-14 months. The efficacy of bendamustine was apparently independent of pretreatment with anthracyclines, suggesting a lack of cross-resistance between bendamustine and anthracyclines. It can be concluded that bendamustine in the dose and application schedule used here is active in the salvage therapy of women with advanced breast cancer. The toxicity was acceptable. Future studies have to confirm the data of this pilot trial and to define the role of bendamustine in the combination chemotherapy of metastatic breast cancer that has been suggested by previous trials.

A phase I study of bendamustine hydrochloride administered day 1+2 every 3 weeks in patients with solid tumours

“…Bendamustine is also actively investigated in multiple myeloma where the combination with prednisone proved to be more efficacious than the standard treatment: melphalan and prednisone (time to treatment failure: 14 vs 10 months, P ¼ 0.02) (Pönisch et al, 2006). In solid tumours, BM's lack of cross-resistance with other alkylating agents, its favourable toxicity profile, and the fact that it shows anticancer activity in second line and in the salvage setting in patients with pretreated metastatic breast cancer (MBC) (Höffken et al, 1998;Zulkowski et al, 2002), non-small cell lung cancer (NSCLC) (Reck et al, 1998), and small cell lung cancer (SCLC) (Schmittel et al, 2007) make it a valuable addition to the armamentarium of active anticancer drugs. Recently, a randomised phase III study compared cyclophosphamide, methotrexate, and 5-fluorouracil (CMF) with a comparable schedule in which cyclophosphamide was replaced by BM (BMF).…”

Synthesis and Characterization of Some New Phase Ii Metabolites of the Alkylator Bendamustine and Their Identification in Human Bile, Urine, and Plasma From Patients With Cholangiocarcinoma

“…1) is a promising bifunctional alkylating agent containing a heterocyclic nucleus that induces more long-lasting DNA double-strand breaks than other alkylating drugs (Strumberg et al, 1996). The compound was first synthesized in 1963 with anticipated purine-based antimetabolic activity and has shown preferentially cytotoxic activity in the treatment of hematological malignancies, including non-Hodgkin's lymphoma, chronic lymphocytic leukemia, and multiple myeloma, as well as breast cancer (Höffken et al, 1998;Heider and Niederle, 2001;Kath et al, 2001;Aivado et al, 2002;Bremer, 2002;Konstantinov et al, 2002;Pönisch and Niederwieser, 2002;Weidmann et al, 2002). Moreover, anticancer activity was reported in advanced small cell lung cancer and head or neck tumors (Reck et al, 1998;Rahn et al, 2001).…”

In vitro evaluation of bendamustine induced apoptosis in B-chronic lymphocytic leukemia

“…[23][24][25][26][27][28][29] Bendamustine belongs to the group of bifunctional alkylating agents. The nitrogen mustard group in position 5 is linked to a benzimidazol nucleus, showing a methyl-group in position 1 and a butanoic acid residue in position 2 ( Figure 1).…”