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

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. Received: 9 April 1998 / Accepted: 24 June 1998     

Pneumocystis jiroveci prophylaxis in patients undergoing Bendamustine treatment: the need for a standardized protocol

The decision for PJP prophylaxis depends on a physician's evaluation of multiple variables. The high rate of PJP infection described in this article combined with the known impaired T‐cell function post Bendamustine treatment justifies considering all patients for PJP prophylaxis when they receive Bendamustine treatment.     

Bendamustine plus mitoxantrone--a new effective treatment for advanced chronic lymphocytic leukaemia: results of a phase I/II study

The toxicity and efficacy of the combination bendamustine plus mitoxantrone (BM) was evaluated in 22 patients with advanced chronic lymphocytic leukaemia (CLL). Twenty out of twenty-two patients had received at least one prior regimen. Median age was 71 years (range 53-86). Six out of twenty-two patients were Binet stage B and 16/22 Binet stage C. Bendamustine was given in escalating doses from 80 up to 240 mg/m₂ divided in two to three doses per course, mitoxantrone was given as short infusion with 8 up to 10 mg/m₂ per course. The number of courses was limited to six and chemotherapy stopped when a complete remission (CR) or partial remission (PR) according to NCI-Criteria was achieved. Haematotoxicity and infection were dose limiting with 4/6 patients suffering from grade 3 infectious complication in the bendamustine level with 240 mg/m₂. Six out of twenty-two patients achieved a CR and 13/22 patients a PR resulting in an overall response rate of 86% (19/22 patients). Median time to progression was 10 months (range 4-22) and median survival 39 months (range 6-50). For further studies we recommend a bendamustine dose of 150 mg/m₂ combined with 10 mg/m₂ mitoxantrone.     

Persistent viral shedding of severe acute respiratory syndrome coronavirus 2 after treatment with bendamustine and rituximab: A case report

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA is detectable in nasopharyngeal specimens for up to 12–20 days regardless of the presence of chronic diseases in patients. We report a case of prolonged SARS-CoV-2 infection that lasted for more than eight weeks. The patient had persistent lymphopenia after receiving six cycles of bendamustine and rituximab (BR) therapy for follicular lymphoma; the last chemotherapy session was completed nine months before admission. The first nasopharyngeal specimen (NPS) for the SARS-CoV-2 polymerase chain reaction assay tested positive for the N501Y variant five weeks before admission. The patient's general and respiratory conditions gradually worsened; therefore, he was admitted to our hospital, and the same SARS-CoV-2 variant was subsequently identified on admission. Treatment for coronavirus disease was initiated, and the patient's condition improved; however, the NPS tested positive on day 15. The patient was discharged on day 28 and was instructed to isolate at home for a month. Hence, possible prolonged SARS-CoV-2 shedding should be considered in patients who receive BR therapy.     

Bendamustine, but not fludarabine, exhibits a low stem cell toxicity in vitro

Purpose  We investigated the in vitro toxicity of bendamustine and fludarabine to hematopoietic progenitors and stem cells from healthy donors. Methods  Clonogenic agar colony assays, non-clonogenic long-term liquid cultures (LTC) and apoptosis assays were used to assess the cytotoxicity of both the agents. Results  Total colony-forming units (CFU) were more sensitive to fludarabine than to bendamustine in agar colony assays (IC₅₀ 0.7 μM/L and 8.5 μM/L, respectively). Using the Bliss independence model and combining the two agents yielded additive inhibition of progenitors. Non-clonogenic assays, including LTC and an apoptosis assay detecting activated caspases showed that stem cells are characterized by low sensitivity to bendamustine. In contrast, fludarabine strongly inhibited the viability and growth of stem cells in LTC. Conclusions  Our data show that bendamustine is characterized by lower in vitro toxicity to hematopoietic progenitors and stem cells than fludarabine and might thus be preferable in regimens prior to stem cells apheresis. Part of the data has been presented at the annual meeting of the American Association for Cancer Research (AACR) 2005 (Los Angeles, CA, USA).     

Treatment of Bendamustine and Prednisone in patients with newly diagnosed multiple myeloma results in superior complete response rate, prolonged time to treatment failure and improved quality of life compared to treatment with Melphalan and Prednisone—a randomized phase III study of the East German Study Group of Hematology and Oncology (OSHO)

Purpose: This randomized phase III study compared bendamustine and prednisone (BP) to standard melphalan and prednisone (MP) treatment in previously untreated patients with multiple Myeloma (MM). Patients and Methods: To be included, patients had to have histologically and cytologically proven stage II with progressive diseases or stage III MM. They were randomly assigned to receive BP (n=68) or MP (n=63). The primary endpoint was the time to treatment failure (TTF). Secondary endpoints included survival, remission rate, toxicity and quality of life. Results: The overall response rate was 75% in the BP and 70% in the MP group. A significantly higher number of patients treated with BP achieved a complete remission than did patients receiving MP (32 vs. 13%; P=0.007), and the maximum response was achieved more rapidly in patients treated with BP compared to those receiving MP (6.8 vs. 8.7 cycles; P<0.02). TTF and remission duration were significantly longer in the BP group. Patients receiving BP had higher QoL scores and reported pain less frequently than patients receiving MP. Conclusion: BP is superior to MP with respect to complete remission rate, TTF, cycles needed to achieve maximum remission and quality of life and should be considered the new standard in first-line treatment of MM patients not eligible for transplantation.     

Phase-I/II study to evaluate dose limiting toxicity, maximum tolerated dose, and tolerability of bendamustine HCl in pre-treated patients with B-chronic lymphocytic leukaemia (Binet stages B and C) requiring therapy

Purpose: Bendamustine hydrochloride, an anti-neoplastic agent with unique mechanism of action, is known to cause impressive remissions in relapsed nonHodgkin’s lymphoma and chronic lymphocytic leukaemia (CLL). Optimal bendamustine dosing for CLL patients had not been finally established and a phase I/II study was conducted to determine the maximum tolerated dose (MTD) and dose limiting toxicity (DLT) of bendamustine. Methods: The open-label, single-centre phase I/II study was conducted from March 2001 to September 2002 in Sofia, Bulgaria. The 15 study patients were extendedly pre-treated, but fludarabine-naive (3 female, 12 male, 47–72 years of age, 61 years on average). Bendamustine was given at a starting dose of 100 mg/m² on days 1 and 2 every 3 weeks based on the previous results in lymphoma. Results: Bendamustine was well tolerated in spite of heavy pre-treatment of the study participants. Toxicity corresponded to the known safety profile of bendamustine, with the exception of bilirubin elevation. The level of 110 mg/m² was established as MTD. A bendamustine dose of 100 mg/m² is the recommended dose for further clinical investigations. A 4-week interval is recommended to allow for sufficient recovery. Efficacy results confirmed powerful anti-neoplastic activity of bendamustine even in extendedly pre-treated CLL patients. Based on the remission criteria, nine patients were defined as responders (four CRs, two PR, three NC) and two patients as nonresponders to therapy. Four patients were not evaluable for response, because they had received less than three courses bendamustine. After a follow-up period of 15 months, the four patients with CR were still in remission. One patient with PR had relapsed, the other had ongoing response. Conclusions: Bendamustine is a very active and well-tolerated drug in patients with pre-treated and refractory CLL. Fludarabine-naivity of patients appears to markedly improve their bendamustine tolerability. First-line use of bendamustine is a safe option for CLL-patients requiring treatment, because bendamustine—owing to its unique pharmacodynamics—(1) is highly effective, (2) reasonably safe, and (3) does hardly produce cross-resistance against other anti-neoplastic drugs effective in this indication.