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At least 19 recordsLinked to original sources
PubMed1996

Bendamustine hydrochloride activity against doxorubicin-resistant human breast carcinoma cell lines.

The cytotoxic activity of bendamustine hydrochloride was evaluated against human ovarian and breast carcinoma cell lines including cell lines resistant to cisplatin and doxorubicin in vitro. The relative degree of resistance to bendamustine hydrochloride was lower in all cell lines compared with cyclophosphamide, melphalan and BCNU, suggesting only incomplete cross-resistance. Furthermore lower levels of resistance were also observed in all breast cancer cell lines when bendamustine hydrochloride was compared with cisplatin. Bendamustine hydrochloride also presents good activity in cell line MCF 7 AD, which is approximately 80-fold resistant to doxorubicin compared with MCF 7. Basic glutathione levels and activity of glutathione-S-transferase showed no correlation to the IC50 values for bendamustine hydrochloride in the cell lines. When given at equitoxic concentrations, bendamustine hydrochloride consistently induced more DNA double-strand breaks than melphalan, cyclophosphamide or BCNU. In addition, removal of DNA double-strand breaks induced by bendamustine hydrochloride was relatively slow with the majority of DNA double-strand breaks still being detectable after 24 h. These findings indicate differences in the interaction between bendamustine hydrochloride and DNA, and may explain the lack of complete cross-resistance between bendamustine hydrochloride and the other alkylating agents.

Antibiotics, Antineoplastic↗
PubMed1998

[Primary chemotherapy of metastatic breast carcinoma with bendamustine hydrochloride, methotrexate and fluorouracil versus cyclophosphamide, methotrexate and fluorouracil].

The combination bendamustine/methotrexate/fluorouracil (BMF) was proven versus cyclophosphomide/methotrexate/fluorouracil (CMF) in a stratified randomized pilot study as primary chemotherapy in 61 patients with metastatic breast cancer. Bendamustine was given in a dose of 240 mg/m2 and cyclophosphamide in a dose of 960 mg/m2 per therapy-cycle. The doses of methotrexate (40 mg/m2 i.v., day 1 and 8) and fluorouracil (500 mg/m2 i.v., day 1 and 8) were identical in both groups. 25 patients in the BMF- and 24 patients in the CMF-group were evaluable. The remission rates were 52% vs. 46%. The median duration of remission was 15.2 months (ranging from 8.1 to 19.7 months) in the BMF-group and 6.2 months (ranging from 1.9 to 11.1 months) in the CMF-group. The aim of this study was to identify the main criterion for further randomized studies. The results of this pilot study indicate, that it is possible to prolong the median duration of remission without changing the antineoplastic activity by replacing cyclophosphamide with bendamustine.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed2002

Metabolism and mechanisms of action of bendamustine: rationales for combination therapies.

Bendamustine hydrochloride is the active ingredient of Ribomustin (Ribosepharm GmbH, Munich, Germany). It was first synthesized in 1963 in the German Democratic Republic. Bendamustine is chemically related to the alkylating agent chlorambucil, with the benzene ring in the chlorambucil molecule replaced by a 1-methyl-benzimidazole moiety. The mechanisms of action of bendamustine have been under investigation since the early 1960s, and its first use was as a treatment for multiple myeloma in 1969. Bendamustine has three active moieties: an alkylating group, in common with the nitrogen mustard family; a benzimidazole ring, which may act as a purine analog; and a butyric acid side-chain. Bendamustine undergoes extensive first-pass metabolism. However, unmetabolized bendamustine accounts for about 45% of the total drug recovered in urine. The main transformation product is a cytotoxic hydroxy metabolite (beta-hydroxybendamustine). Bendamustine was originally synthesized with the intention of producing an antineoplastic agent with low toxicity and both alkylating and antimetabolic properties. However, it has been shown that, at least at high concentrations, it acts primarily as an alkylating agent. Based on the multiple actions and cell cycle effects of this agent, mechanism-based combination strategies have been suggested. The rationales behind bendamustine combination regimens and the importance of the sequence of administration of different drugs are explored.

Antimetabolites, Antineoplastic↗
PubMed1985

Toxicity of the alkylating agent bendamustin.

In acute toxicity studies the maximum tolerated dose (MTD), the LD50 and the LD100 of Bendamustin were determined in rats and mice after i.v. and oral administration. In a subchronic study male rats were given Bendamustin for 28 days at oral dose levels of 5, 10, 20 or 40 mg/kg/day. Chlorambucil was used as a standard at dose levels of 1, 5 and 10 mg/kg/day. Bodyweight gain, food and water intake, hematology, clinical chemistry and histopathology were evaluated. With quantitative differences the main target organs for both compounds were the bone marrow, the kidney, the intestine and the lymphatic system. Additionally, Chlorambucil caused a significant atrophy of the testes and a slight atrophy of the pancreas at a dose of 5 mg/kg/day. In conclusion, the data obtained may be used as a base to evaluate the therapeutic range of Bendamustin compared to Chlorambucil for the oral route.

Alkylating Agents↗
PubMed2001

[Palliative radiochemotherapy with Bendamustin for advanced recurrent head and neck tumors].

BACKGROUND: In case of recurrent carcinoma of the head and neck region therapeutic options are often limited due to intensive prior therapy and/or reduced physical condition of the patient. Nevertheless there is a need for palliative treatment to control symptoms like pain, obstruction of the airways, dysphagia and for hygienic and cosmetic reasons. Side effects, treatment time and achievable results have to be adjusted to the needs of this patient subgroup. PATIENTS AND METHOD: 14 patients (13 male, one female) with recurrent squamous cell carcinoma of the head and neck region were studied. Average age was 56.1 years (range 42-76 years) (Table 1). Prior therapy: radiotherapy n = 14 (42-71.3 Gy), surgery: n = 10, chemotherapy: n = 13 (Table 2). Our patients received 100-150 mg/m2 Bendamustin i.v. (day 1 and 2) and involved field irradiation 15 Gy (daily dose 3 Gy, day 1-5) (Figure 1). Remission status, time to progression, side effects and survival were documented. RESULTS: Ten patients showed partial remissions, four patients had complete remissions of the treated lesion (Figure 2), amelioration of 70% of tumor symptoms was documented (Figure 3). Time to progression was 2-104 weeks. Side effects: 71% of patients had no significant side effects, CTC Grade 3 to 4 toxicity was seen in two patients (14%). CONCLUSION: The reported therapy regimen allows successful palliative treatment of intensively pretreated patients with progressive recurrent tumors of the head and neck. Side effects are tolerable even in patients with reduced physical condition.

Adult↗
PubMed2000

Repeated administration of short infusions of bendamustine: a phase I study in patients with advanced progressive solid tumours.

PURPOSE: The cytotoxic agent bendamustine combines a purine-like benzimidazol and bifunctionally alkylating nitrogen mustard group. The drug has clinical antitumour activity in lymphoma, myeloma and breast cancer. In earlier dose-finding studies, the clinically tolerated dose for single-bolus bendamustine was 215 mg/m2; for fractionated therapy on 4 consecutive days it was 85 mg/m2. Anticholinergic symptoms, myelosuppression and cardiac dysrhythmia were dose-limiting. Our trial was designed to define the maximum tolerated dose of a short infusion schedule and to establish a recommended dose for ongoing and future clinical studies. METHODS: Patients with refractory malignant tumours qualified for the trial after written informed consent had been obtained. Bendamustine was given as a 30-min iv. infusion on days 1 and 8 of a 4 week cycle, with a starting dose of 100 mg/m2 and an increment per group of 20 mg/m2. RESULTS: Nineteen patients (13 male, 6 female; median age 57 years, range 37-74 years) were treated for one to two cycles with up to 180 mg/m2 bendamustine. At 160 mg/m2, fatigue grade 3 (NCI Common Toxicity Criteria) and dryness of the mouth grade 3 occurred in 2 patients, diarrhoea grade 3 in 1 patient; another patient with a history of myocardial infarction and arrhythmia developed a reversible total atrioventricular block after the first administration of 160 mg/m2 bendamustine. Other events, such as nausea/vomiting, loss of appetite, fever or chills, were not dose-limiting. Haematological toxicity was mild, except for sudden and long-lasting grade 3-4 lymphocytopenia, which occurred in all treatment cycles. Opportunistic infections were not observed. CONCLUSIONS: The maximum tolerated dose of a days-1 and -8 schedule of bendamustine, given as a 30-min i.v. infusion, is 160 mg/ m2; mouth dryness and fatigue are dose-limiting. The recommended dose for future trials is 140 mg/m2.

Adult↗
PubMed2001

Effective treatment with rituximab in a patient with refractory prolymphocytoid transformed B-chronic lymphocytic leukemia and Evans syndrome.

A 65-year-old male who had been diagnosed as having chronic lymphocytic leukemia (CLL) stage Rai 0 three years previously presented in October 1998 with progressive disease (splenomegaly, increasing lymphocytosis: 30/nl) and 50% prolymphocytes in his peripheral blood. The patient was refractory to initial treatment with fludarabine and epirubicin, and 2-chlorodeoxyadenosine. Additionally, the patient developed Evans syndrome. Therapy with cyclophosphamide, vincristine, and prednisone lead to an improvement of hemolysis, but the patient remained thrombocytopenic. Subsequently, lymphocytes further increased to 135/nl, and cyclophosphamide 3 g/m2 was again given but without effect on the peripheral lymphocyte count. At this stage, therapy with rituximab 375 mg/m2 four times weekly was initiated. The platelet count normalized within 1 week after the first dose of rituximab, and the lymphocyte count dropped within 2 months to 1.1/nl. This case demonstrates that patients with prolymphocytoid transformed B-CLL refractory to purine analogs and alkylating agents and autoimmune-hemolytic disease can effectively and safely be treated with rituximab and indicates that an investigation of antibody therapy is warranted in this patient group.

Aged↗
PubMed2001

Regression of brain metastases from breast carcinoma after chemotherapy with bendamustine.

PURPOSE: Bendamustinehydrochloride (bendamustine) is an alkylator with anticipated antimetabolic activity. It has shown activity in malignant lymphoma and breast cancer. Up to now there are no reports about the activity of bendamustine in the treatment of brain metastases. We report on a 38-year-old woman with brain metastases from breast cancer. The first diagnosis of an invasive ductal, hormone receptor negative breast cancer was made in October 1997, stage pT1c pN2 (11/11)cM0 - G3. After lumpectomy and resection of axillary lymph nodes, the patient received adjuvant chemo- and radiotherapy. Twenty six months after the first diagnosis, bone metastases occurred and were treated with radiotherapy. One month later, multiple liver metastases developed which were treated with trastuzumab and paclitaxel. Four months later, progress of the liver metastases and malignant infiltration of bone marrow with thrombopenia occurred. METHODS: Chemotherapy with bendamustine at a dose of 150 mg/m(2) on day 1 and 2 was initiated. Two days later, the patient suffered from central facial palsy and subsequent computed tomography (CT) revealed three brain metastases in the frontal, parietal and occipital region. Because of the advanced liver metastases with clinical and laboratory signs of liver insufficiency and the reduced performance status of the patient, chemotherapy with bendamustine was continued and no local treatment of the brain metastases was performed. RESULTS: After two courses of bendamustine, ultrasound showed regression of the liver metastases. Liver enzymes decreased, platelets increased, and the patient's performance status improved. Additionally, two of the three brain metastases were no longer detectable by CT, the third had decreased compared to the time of diagnosis. CONCLUSION: To the best of our knowledge, this is the first report describing major activity of bendamustine in cerebral metastases. Thus, it may be considered as another therapeutic strategy against metastatic brain cancer. However, this finding warrants further investigation in clinical trials.

Adult↗
PubMed2002

Cytotoxic efficacy of bendamustine in human leukemia and breast cancer cell lines.

PURPOSE: The purpose of this study was to characterise bendamustine's cytotoxic and apoptotic activity in a panel of leukemia and breast cancer cell lines in comparison to its clastogenicity in murine bone marrow. METHODS: The cytotoxic effect of bendamustine was measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT)-dye reduction assay. Induction of apoptosis was evidenced by DNA gel electrophoresis, nuclear staining, Western blot poly-(adenosine diphosphate-ribose) polymerase (PARP) cleavage, and flow cytometry. As a measure of hematological toxicity, the formation of chromosomal aberrations was investigated in bone marrow cells isolated from mice treated with low non-toxic doses of bendamustine and lomustine. RESULTS: Bendamustine was preferably active against leukemic cells of lymphoid origin and was found to induce apoptosis in SKW-3 and BV-173 cells as shown by oligonucleosomal DNA and nuclear fragmentation, PARP cleavage, and formation of a sub-G1 fraction. Myeloid and breast carcinoma cell lines were resistant towards bendamustine with the exception of HL-60 cells which exhibit an intermediate sensitivity. Bendamustine was found to have a very low clastogenic effect as compared with equimolar doses of lomustine. CONCLUSION: Taken together, the mode of action of bendamustine includes induction of apoptosis. The specific spectrum of activity and the unexpectedly low clastogenicity support the hypothesis that bendamustine in not a typical alkylating agent but exerts an additional mode of action, possibly as a purine antimetabolite.

Animals↗
PubMed2002

High rates of long-lasting remissions after 5-day bendamustine chemotherapy cycles in pre-treated low-grade non-Hodgkin's-lymphomas.

PURPOSE: Since continuous relapse rates are characteristic for advanced low-grade non-Hodgkin's lymphomas (NHL), their treatment remains a problem. Previous phase II studies showed that bendamustine induced high remission rates in pre-treated low-grade NHL. To further examine its efficacy and side effects, bendamustine has been studied in a large number of patients with pre-treated low-grade NHL. Follow-up time was 3-8 years. METHODS: From 1993 to 1998, 102 patients with pre-treated low-grade NHL [histologic subtypes: CLL n=15, immunocytic n=46, multiple myeloma (MM) n=25, others n=16] received a median of four (range 1-11) 5-day cycles of daily 60 mg/m(2) bendamustine as salvage chemotherapy. Bendamustine was given in short i.v. infusions mainly at intervals of 4-6 weeks. RESULTS: Partial and complete remissions were observed in 76.5% and disease stabilization in 19.6% of the patients. Only 3.9% showed progressive disease. Median duration of response was 39 months for the NHL patients and 17 months for the MM patients. Median survival time was 32 months for the CLL patients, 31.5 months for the NHL patients and 17.5 months for the MM patients. Non-haematological side effects consisted mainly in reversible reduction of performance status, loss of appetite, and nausea/vomiting and diarrhoea, which were of WHO grade III/IV in less than 5% of patients. Haematological toxicities of WHO grade III/IV have been observed in 6.9%, 11.8%, and 24.5% of patients for hemoglobin, thrombocytes, and leukocytes, respectively. Alopecia did not occur. Febrile episodes or bacterial as well as viral, particularly opportunistic, infections were not observed, although bendamustine induced profound and long-lasting lymphocytopenias, including CD4+-, CD8+-, CD19+-, B-lymphocytes, and NK-cells. CONCLUSIONS: Bendamustine proved to be very effective in pre-treated low-grade NHL patients by inducing high rates of long-lasting remissions. Bendamustine combines the pharmacological properties of an alkylating agent with those of a purine analogue and showed no cross-resistance to chlorambucil, melphalan, cyclophosphamide, mitoxantrone, and other anthracyclines. The myelosuppressive toxicities were dose limiting, and the non-haematological side effects were moderate.

Adult↗
PubMed2003

Pneumocystis carinii pneumonia as a complication of bendamustine monotherapy in a patient with advanced progressive breast cancer.

BACKGROUND: Bendamustine is an alkylator with anticipated antimetabolic activity. It has shown activity in malignant lymphoma, multiple myeloma, and breast cancer. Recognized side-effects are relatively mild with myelosuppression as the dose-limiting toxicity. The CD4/CD8 ratio may be reduced. To what extent the alteration of lymphocytes, especially CD4(+) lymphocytes, correlates with an increase in opportunistic infections cannot be definitively answered. CASE REPORT: The patient, female, aged 48 years, was suffering from an advanced progressive breast cancer. After initial treatment with several chemotherapies, a cytotoxic therapy was initiated, with bendamustine (150 mg/m(2)) administered on two consecutive days and repeated every 4 weeks. After five courses, the patient developed Pneumocystis carinii pneumonia (PCP), disclosed in the bronchoalveolar lavage. While receiving bendamustine therapy, the CD4(+) and CD8(+) lymphocyte counts in the peripheral blood were determined by flow cytometry. The next-to-normal CD4/CD8 ratio before therapy (0,82) had decreased to 0,05 during the therapy mainly due to a decline of CD4(+) lymphocyte. The patient was seronegative for human immunodeficiency virus. In spite of high-dose intravenous trimethoprim/sulfamethoxazole and methylprednisolone application, the patient died of a respiratory failure 3 days after PCP was diagnosed. CONCLUSION: Bendamustine is capable of inducing a reduction in CD4(+) lymphocyte counts causing a severe T-lymphocyte-mediated immunosuppression. Measuring CD4(+) lymphocyte counts may be helpful in determining the risk of PCP in patients treated with bendamustine.

Antineoplastic Agents↗
PubMed2001

Bendamustine monotherapy in advanced and refractory chronic lymphocytic leukemia.

Bendamustine, an alkylating agent without cross-resistance to cyclophosphamide is active in a variety of lymphoproliferative and other malignancies. In an open phase-II study we treated 23 patients with a median age of 62 years at study entry (43-86 years) with advanced, refractory or relapsed (Rai stage III n = 9, Rai stage IV n = 14) chronic lymphocytic leukemia (CLL) with bendamustine. At study entry, only 13 patients were chemotherapy-naive. The treatment schedule with bendamustine was as follows: for patients up to 70 years 60 mg/m2 for 5 days, for patients over 70 years 50 mg/m2 for 5 days, repetition at day 29. Remission criteria were used according to Cheson et al. (1996). All patients were evaluable for toxicity and 20 for response. An objective remission was achieved in 15/20 patients (75%), including six patients with complete remission (CR). Three of the complete responders had no chemotherapy prior to bendamustine. No change (NC) occurred in 5/20 patients (25%). Median overall survival after bendamustine treatment is 13.6 months (1-46 months) and 16.6 months (1-46 months) in patients responding to bendamustine. In total, 74 courses of bendamustine were applied. Therapy-related anemia and thrombocytopenia were rare. However, WHO grade III/IV leukocytopenia occurred in 38/74 cycles (51%), resulting in treatment-related mortality in 3/23 patients (13%). These patients were severely immunocompromised due to pretreatment or the underlying disease. As a corollary of the study, a general prophylactic antibiotic treatment (trimethoprim/ sulfamerazine) was instituted. A general feature was the decline of the CD4/CD8 ratio: mean before therapy: 1.36; after two courses: 0.98; after four courses: 0.6, as documented in all patients who received at least two courses of bendamustine (n = 12). All evaluable patients showed a decline in the CD4/8 ratio. However, this decline was not clearly related to an increased risk of infectious episodes. We observed mainly cutaneous allergic reactions (three WHO grade I; one WHO grade II) leading to a cessation of bendamustine treatment in 4/23 patients (18%). Bendamustine is highly effective in advanced or refractory CLL. In multiple pretreated or otherwise severely immunocompromised patients bendamustine might lead to additional immunosuppression with subsequent infectious complications.

Adult↗
PubMed1998

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.

Adult↗
PubMed1980

Effect of a membrane-stabilizing compound on calcium binding to the plasma membrane of Acanthamoeba castellanii.

Binding of calcium ions at the plasma membrane was studied in Acanthamoeba cells pretreated with ZIMET 3164, a benzimidazole nitrogen mustard derivative, which is known to show a potent immunosuppressive action combined with a membrane-stabilizing effect in mice. For reference, 2 compounds were applied: ZIMET 3393 (Cytostasan¿), another benzimidazole mustard derivative, which exerts only a moderate membrane effect and acts as a strong cytostatic, and ZIMET 176/68, a barbituric acid derivative, which acts as an inhibitor of humoral immune responses but without membrane-stabilizing effect. Application of any of the 3 compounds does not reduce the appearance of calcium binding sites, visualized by means of ultracytochemical reaction, notwithstanding their different action in the mammalian organism. On the contrary, it was estimated by morphometric analysis that the number of Ca-dependent deposits was augmented after treatment with low doses of any of the 3 compounds, what seems to be connected with the induced metabolic disturbances in low molecular phosphates level. High doses and/or prolongation of treatment of the cells resulted in diminution of the number of deposits and induces profound disturbances in cell ultrastructure, probably due to the toxic action of the applied doses. In these cases, band-like structures crosslinking the two leaflets of the plasma membrane may be observed; it is suggested that they represent integral membrane proteins.

Amoeba↗
PubMed2000

Weekly administration of bendamustine: a phase I study in patients with advanced progressive solid tumours.

BACKGROUND: The cytotoxic agent bendamustine combines a purine-like benzimidazol and alkylating nitrogen mustard group. The clinically tolerated dose for single bolus bendamustine is 215 mg/m2, for fractionated therapy on four consecutive days 85 mg/m2. The maximum tolerated dose of a day 1 and 8 (q4w) 30 min infusion schedule was recently found to be 160 mg/m2, mouth dryness and fatigue were dose-limiting. Our current phase I trial was designed to define the recommended dose of a new weekly short infusion schedule. PATIENTS AND METHODS: Patients with refractory malignant tumours qualified for the trial after written informed consent was obtained. Bendamustine was given as a 30-min i.v. infusion weekly for up to eight consecutive weeks. RESULTS: Twelve patients (8 male, 4 female, median age 57.5 years, range 42-64) were enrolled in this trial. At the starting dose of 80 mg/m2, two patients had dose-limiting toxicity (fatigue grade 3, mouth dryness grade 3, fever grade 4 Common Toxicity Criteria). No dose-limiting events were observed in six patients treated at 60 mg/m2. An intermediate dose level of 70 mg/m2 was studied in three younger, less heavily pretreated patients, was well tolerated and not associated with dose-limiting events. Haematological toxicity was mild except for grade 3-4 lymphocytopenia, occurring in 11 of 12 patients. Bendamustine was found to induce long-lasting panlymphocytopenia with predominant B-cell cytotoxicity. CONCLUSIONS: The maximum tolerated dose of weekly bendamustine given as a 30-min i.v. infusion is 80 mg/m2, mouth dryness, fatigue and fever are dose-limiting. The recommended dose for phase II trials is 60 mg/m2.

Adult↗
PubMed2002

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

Bendamustine is a novel cytostatic agent, with activity in non-Hodgkin's lymphomas including B-chronic lymphocytic leukemia (B-CLL). The knowledge about its mode of action, however, is still limited. Here, we investigated the in vitro ability of bendamustine to induce apoptosis on freshly isolated peripheral lymphocytes in B-CLL and analyze the potential underlying mechanisms of action for inducing apoptosis. In CLL cells taken from 37 previously treated and untreated CLL patients, we investigated the influence of bendamustine alone, and in combination with fludarabine, on the induction of apoptosis and changes of Bcl-2 and Bax expression on mRNA and protein level using the RNase protection assay or flow cytometry, respectively. Apoptotic cells were determined with flow cytometry using the fluorescent DNA-binding agent 7-ADD. Using bendamustine alone in concentrations from 1 microg/ml to 50 microg/ml, a dose- and time-dependent manner of cytotoxicity from 30.4% to 94.8% after 48 h could be observed. The LD50 for untreated and pretreated CLL cells was 7.3 or 4.4 microg/ml, respectively. The median apoptotic rate was similar in both groups. The combination of bendamustine with fludarabine led to a highly synergistic effect in inducing apoptosis, which was 150% higher than expected for bendamustine plus fludarabine. The level of the initial Bcl-2 and Bax protein and the m-RNA expression remained unchanged during the incubation with bendamustine. In conclusion, this study demonstrates for the first time the in vitro efficacy of bendamustine in inducing apoptosis in B-CLL cells alone and in combination with fludarabine.

Antineoplastic Agents↗