PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Bendamustine Hydrochloride”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2Linked to original sources
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↗
PubMed2006

Phase II trial of second-line bendamustine chemotherapy in relapsed small cell lung cancer patients.

PURPOSE: The efficacy and toxicity of bendamustine chemotherapy in relapsed small cell lung cancer (SCLC) was determined in this phase II trial. PATIENTS AND METHODS: Patients with cytologically or histologically proven SCLC, who had a sensitive relapse, which was defined as a relapse>or=2 months after completion of primary therapy, were eligible for this study. After informed consent patients received 120 mg/m2 of bendamustine on Days 1 and 2 every 3 weeks. A maximum of six cycles was administered. Primary endpoint was response rate, secondary endpoints included toxicity, progression free survival and overall survival (OS). RESULTS: Twenty-one patients with a median age of 59 years (range 47-76) were accrued to this trial. Six (29%) of 21 patients achieved a confirmed partial remission, 6 (29%) had stable disease and 9 (42%) patients progressed according to RECIST criteria. Median progression free survival was 4 months (95% CI 0-8, 3), median overall survival was 7 months (95% CI 5, 8-8, 2). One- and 2-year survival was 16% and 8%, respectively. Grade III/IV neutropenia occurred in 3 (15%) of 21 patients, 1 patient had a lethal Gram-negative sepsis in neutropenia. Two additional patients had pneumonia in the absence of neutropenia. Two patients (10%) had a grade III anemia, no grade III or IV thrombocytopenia was observed. CONCLUSION: This trial demonstrates efficacy of bendamustine in relapsed SCLC and a favourable toxicity profile. Therefore, single-agent bendamustine is a treatment option for patients with SCLC, who have responded to initial platinum containing chemotherapy and should further be investigated in randomized trials.

Aged↗
PubMed2003

Synergistic effects of chemotherapeutic drugs in lymphoma cells are associated with down-regulation of inhibitor of apoptosis proteins (IAPs), prostate-apoptosis-response-gene 4 (Par-4), death-associated protein (Daxx) and with enforced caspase activation.

Cytotoxic drugs mediate apoptotic tumor cell death by influencing key regulator proteins of programmed cell death. In clinical practice cytotoxic drug combinations are desired to potentiate tumor cell kill and to minimize side effects. Nevertheless, the molecular mechanisms underlying synergistic and antagonistic effects on tumor cells are still poorly understood. In order to elucidate these molecular mechanisms we established models of synergistic and antagonistic drug combinations within the same lymphoma cell lines. By combination index method we demonstrated that bendamustine in combination with either doxorubicin or mitoxantrone caused antagonistic effects on disruption of mitochondrial membrane potential as well as on the rate of apoptosis. In contrast the combination of bendamustine with cladribine acted synergistically on these parameters. By using the IC(50) (dosages causing 50% rate of apoptosis) the synergistic effect of the combination of bendamustine and cladribine was associated with an enhanced mitochondrial release of cytochrome c and Smac/DIABLO, by down-regulation of x-linked inhibitor of apoptosis (XIAP), cIAP1, Par-4 and Daxx as well as by a significantly increased activation of caspases-3, -6, -7, -8 and -9. At the same rate of apoptosis (IC(50)), the antagonistic combinations did not increase the release of cytochrome c or Smac/DIABLO, nor down-regulate the expression of XIAP, cIAP1, Par-4 and Daxx, nor increase the activation of caspases. The role of down-regulation of IAPs and of enforced caspase activation for synergism in this model was supported by the observation, that broad spectrum inhibition of caspases re-established expression of XIAP. Our study is the first to outline the molecular alterations caused by synergistic and antagonistic drug combinations within the same lymphoma cell model. The above described mechanisms were already assessable at a point where the effects of synergistic or antagonistic combinations could not yet be discriminated quantitatively by the level of apoptosis rate of the lymphoma cells.

Adaptor Proteins, Signal Transducing↗
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↗
PubMed2004

Advances in chemotherapy for chronic lymphocytic leukemia.

While chemotherapy based on alkylating agents has been the standard treatment of chronic lymphocytic leukemia (CLL) for decades, purine analogues and their combinations have emerged as effective new therapies for previously untreated and pretreated patients. As single agents, fludarabine and cladribine are the most promising, showing higher remission rates compared to chlorambucil. For younger and physically fit patients, the combination of fludarabine and cyclophosphamide has shown benefit. Fludarabine plus epirubicin appears equally potent. The addition of monoclonal antibodies, such as rituximab and alemtuzumab, to purine analogues alone or in combination seems to be even more effective for chemotherapy-naive and pretreated CLL patients. Another promising agent in the armamentarium of therapies for CLL is bendamustine, which has properties of both an alkylating agent and a purine analogue. Clinical trials are ongoing with novel drugs that interfere with cell cycle regulation and signaling molecules in CLL, including flavopiridol, UCN-01, bryostatin 1, depsipeptide, and oblimersen. It remains to be seen whether these chemotherapeutic approaches offer real benefit for patients by prolonging survival with an improved quality of life.

Alkylating Agents↗
PubMed2002

In vitro studies with bendamustine: enhanced activity in combination with rituximab.

Studies in vitro have shown that bendamustine, given as a monotherapy or in combination, can induce apoptosis in many cell types, including B-cell chronic lymphocytic leukemia and low-grade lymphoma cells. Evidence is accumulating to suggest that bendamustine may also have synergistic effects in combination therapies. Rituximab is a promising new agent for the treatment of hematologic malignancies and has been shown to have synergistic actions with other chemotherapeutic agents. The actions of the combination of bendamustine and rituximab on ex vivo B-cell chronic lymphocytic leukemia cells and the DOHH-2 cell line, derived from CD20-positive lymphoma cells, are discussed in this article.

Antibodies, Monoclonal↗
PubMed2002

Phase I studies with bendamustine: an update.

Bendamustine is a novel agent with both alkylating and purine-like moieties that is currently in phase II/III trials for the treatment of hematologic malignancies and breast, lung, and gastrointestinal tumors. Bendamustine was developed in the early 1960s and first used clinically in 1969 in patients with multiple myeloma. Since then, various dose and treatment schedules have been used empirically. Although bendamustine has been in clinical use for over three decades, the early clinical trials do not conform to present-day standards of good clinical practice. Therefore, it was necessary to conduct a full range of clinical trials before application for a European marketing license could be made. To date, bendamustine has been investigated both as a single agent and in combination with other anticancer drugs, in phase I, II, and III clinical trials. This article presents an overview of the recent phase I trials and a summary of ongoing clinical trials.

Antineoplastic Agents↗
PubMed2002

Bendamustine in the treatment of chronic lymphocytic leukemia: results and future perspectives.

Chronic lymphocytic leukemia (CLL) occurs predominantly in elderly patients. The treatment options for patients with CLL have increased with the introduction of purine analogs, and promising results have been reported with fludarabine and cladribine when these agents are used in newly diagnosed and relapsed disease. Monoclonal antibodies such as alemtuzumab and rituximab are also clinically active in CLL. The use of purine analogs in combination with monoclonal antibodies may provide additional treatment options and this strategy is being studied in patients with relapsed and refractory CLL. Bendamustine is an alkylating agent with properties of a purine analog and is a promising agent in the treatment of CLL. Bendamustine reduces the number of circulating B lymphocytes by over 90% and shows only partial cross-resistance with other alkylating agents, making it an ideal candidate for the treatment of CLL and for use in combination with other alkylating agents. Bendamustine monotherapy can be given to patients whose disease is refractory to standard therapies. The results of a trial using bendamustine as a salvage treatment in patients with relapsed or refractory, heavily pretreated CLL are discussed here. Bendamustine 100 mg/m(2) (days 1 and 2) was found to be an effective treatment for older patients with advanced CLL, with 14 of 21 patients responding. Complete hematologic remission was achieved in six of 21 patients and a further eight patients achieved a partial hematologic remission. The main toxicities were hematologic; nonhematologic side effects were mild and uncommon.

Aged↗
PubMed2002

Bendamustine in the treatment of multiple myeloma: results and future perspectives.

Multiple myeloma (MM) is a malignancy of terminally differentiated plasma cells typically occurring in elderly patients. The clinical manifestations of this disease result primarily from the accumulation of monoclonal protein (paraprotein) in the serum and/or urine, anemia, lytic bone lesions, hypercalcemia, renal insufficiency, and immune deficiency. Multiple myeloma is incurable with standard chemotherapy. Melphalan and prednisone has been the mainstay of treatment for MM for about three decades. This regimen results in a clinical response in approximately 60% of patients and a median survival of approximately 36 months. A variety of combination therapies have also been used in MM, but have not been considered to offer a significant benefit compared with standard therapy. In early trials, bendamustine monotherapy was as effective as cyclophosphamide and various combination therapies in achieving remission in MM. This article describes a prospective, randomized, phase III study designed to compare the efficacy of bendamustine/prednisolone with a standard melphalan/prednisolone regimen.

Adult↗
PubMed2002

Bendamustine in the treatment of non-Hodgkin's lymphoma: results and future perspectives.

Bendamustine has clinical potential in the treatment of low-grade non-Hodgkin's lymphoma (NHL). As a single agent, bendamustine has been used in two studies in patients with relapsed or refractory low-grade NHL. When bendamustine 120 mg/m(2) was given on days 1 and 2, the overall response rate was 73% with complete responses in 11%. When bendamustine 50 to 60 mg/m(2) was given on days 1 through 5, the overall response rate was 82.5%, with 14.5% complete responses. Bendamustine shows only partial cross-resistance with other agents used in the treatment of NHL and combination regimens have been investigated. The combination of bendamustine/vincristine/prednisolone (BOP) has been compared with cyclophosphamide/vincristine/prednisolone (COP) in a phase III study involving 162 patients with low-grade NHL. No differences were seen between the treatment arms with regard to response rate or survival, but the BOP regimen was significantly better tolerated than the COP regimen. The combination of rituximab/bendamustine has shown encouraging activity in patients with relapsed/refractory NHL and a trial is ongoing in which this combination is used in patients with advanced low-grade NHL or mantle cell lymphoma. Preliminary results from this trial are presented. The 93% overall response rate attained in the patients presently evaluable indicates that this combination is very active in this poor-prognosis population. Optimal treatment regimens with bendamustine in the treatment of low-grade NHL are yet to be defined, but results obtained to date indicate that further studies are warranted.

Antibodies, Monoclonal↗
PubMed2002

Hematologic malignancies: new developments and future treatments.

An increasing number of unique active new chemotherapeutic and biologic agents are currently available for clinical research studies. Nucleoside analogs in development for non-Hodgkin's lymphoma (NHL) include clofarabine, troxacitabine, and bendamustine, a hybrid of an alkylating nitrogen mustard group and a purine-like benzimidazole, with demonstrated activity in NHL. Drugs directed at the cell cycle include flavopiridol and UCN-01. The proteasome plays a pivotal role in cellular protein regulation and activation of NFkappaB, which maintains cell viability through the transcription of inhibitors of apoptosis. PS-341 is a specific, selective inhibitor of the 26S proteasome which induces apoptosis and has activity in cell types characterized by overexpression of Bcl-2. Response rates of 50%, including complete remissions, have been reported using this agent in patients with refractory multiple myeloma. Studies are ongoing in NHL and chronic lymphocytic leukemia. G3139, an antisense oligonucleotide, has shown promise in early studies. Rituximab has revolutionized the treatment of NHL. However, other active antibodies are now available, including alemtuzumab, epratuzumab, and Hu1D10. The radioimmunoconjugates (90)Y-ibritumomab tiuxetan and (131)I-tositumomab may also play an important role in the management of NHL. Future therapeutic strategies should involve rational combinations of new chemotherapy drugs, biologic agents, and antisense compounds to increase the cure rate in patients with lymphoma.

Adenine Nucleotides↗
PubMed2002

Bendamustine mitoxantrone and rituximab (BMR): a new effective regimen for refractory or relapsed indolent lymphomas.

Bendamustine (B) and mitoxantrone (M) have been shown to be potent cytotoxic drugs for the treatment of relapsed or refractory indolent lymphomas. The anti-CD20 monoclonal antibody rituximab (R) has produced an overall response rate (ORR) of 50% as a single agent in relapsed or refractory indolent lymphomas. We posed the question whether a combination of the above agents (BMR) could improve these results. This study was an open label, single center pilot study for patients with relapsed or refractory, CD20-positive (indolent) lymphoma or chronic lymphocytic leukaemia. The therapy consisted of bendamustine (80 mg/m2, day 1-3), mitoxantrone (10 mg/m2, day 1), rituximab (375 mg/m2, week 2-5). BM was repeated on day 36 or when the haematological parameters had recovered. The maximum therapy consisted of one BMR-cycle, followed by five BM courses. Treatment was stopped when the disease responded with PR/CR. During March 1999 and December 2000, 20 patients received the BMR-regimen (four secondary high grade lymphoma, 12 indolent lymphoma, four B-CLL). The median age of the patients was 67 years (range 36-82) and their performance status ranged from 0 to 3. Median number of previous treatment regimens was two (1-6). Of the lymphoma patients, 14 had stage IV disease, 1 stage III and 1 stage II. B-CLL patients were all Rai stage IV (Binet C). Overall response rate was 95% (19/20) with seven patients achieving a CR (35%) and 12 patients achieving a PR (60%). Median time to progression is 7 months (1-21) with a median observation time of 7 months (1-21). Response is still durable in 15/20 patients (75%) (1+ to 21+ months after therapy). Symptomatic, reversible grade three or four haematotoxicity occurred in 4/20 patients (20%). Non-symptomatic grade three or four haematotoxicity was seen in 9/20 patients (45%). No major non-haematological toxicity was observed. In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory indolent lymphoid malignancies.

Adult↗
PubMed2004

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

The toxicity arid 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.

Aged↗