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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↗
PubMed2006

Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride.

PURPOSE: The metabolism of bendamustine (BM) hydrochloride, a bifunctional alkylator containing a heterocyclic ring, was investigated in vitro and in vivo for identification of cytochromes P450 (CYP) involved in the formation of two phase I metabolites, structural confirmation of these previously unidentified metabolites and assessment of their cytotoxic effect in relation to the parent compound. METHODS: Potential metabolites of BM were synthesized and structurally characterized by nuclear magnetic resonance (NMR) and liquid chromatography-mass spectrometry (LC-MS) analysis. In vitro metabolism of BM hydrochloride in human hepatic microsomes was conducted to identify the CYP450 isoenzymes involved in the oxidative metabolism of BM. Samples from cancer patients after treatment with BM hydrochloride and microsomal preparations were analyzed by LC-MS and HPLC with fluorescence detection. The cytotoxic effect of the metabolites was analyzed in several lymphoma cell lines and peripheral blood lymphocytes and compared with that of the parent compound using an MTT assay. RESULTS: LC-MS as well as HPLC with fluorescence detection revealed hydroxylation of the methylene carbon at the C-4 position of the butanoic acid side chain and N-demethylation of the benzimidazole skeleton as the main metabolic pathways in human liver microsomes. Isoform-specific chemical inhibitors and correlation analysis pointed to CYP1A2 as the prominent enzyme in BM oxidation. The rate of formation for both metabolites correlated (r=0.931 and 0.933) with the activity of CYP1A2 and there were no other notable correlations with any of the other CYPs. In addition, both metabolites were identified in plasma, urine, and bile samples from cancer patients under BM hydrochloride therapy as shown by comparison with chromatograms obtained from the authentic reference standards. Cytotoxic activity observed for gamma-hydroxy BM was approximately equivalent to that obtained for the parental compound BM. N-demethyl BM displays five to tenfold less cytotoxic activity than BM. CONCLUSION: The results indicate that CYP1A2-catalyzed N-dealkylation and gamma hydroxylation are the major routes for BM phase I metabolism producing two metabolites less or similarly toxic than the parent compound. In contrast to the metabolic pathways of the structurally related chlorambucil, no beta-oxidation of the butanoic acid side chain leading to enhanced toxicity was detected for BM.

Aged↗
PubMed2005

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.

Two i.v. regimens, bendamustine, methotrexate and 5-fluorouracil (BMF) and cyclophosphamide, methotrexate and 5-fluorouracil (CMF) were compared as first-line therapy in a randomized, open, multicenter phase III trial including 364 patients with metastatic breast cancer (MBC). Bendamustine is an anti-neoplastic agent with alkylating, but also additional, so far unclear, mechanisms of action. We wanted to show the superiority of BMF over CMF in terms of time to progression (TTP) (primary endpoint), overall response, response duration, toxicity and quality of life (QoL). TTP was significantly longer in the BMF group (8.2 versus 6.7 months for CMF) (p=0.0071). The effect of BMF on TTP was more pronounced in the stratum 'prior adjuvant therapy, no visceral metastases' (p=0.034). Overall response rates and QoL did not significantly differ between the regimens. BMF caused more mucositis and leukopenias. Thus, bendamustine, when replacing cyclophosphamide in the CMF combination, can be expected to produce longer progression-free survival in first-line treatment of MBC.

Adolescent↗
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↗
PubMed2004

A phase II study of bendamustine chemotherapy as second-line treatment in metastatic uveal melanoma.

Uveal melanoma is the most frequent primary malignant neoplasm of the eye and has a poor prognosis in metastatic stage. Fotemustine or a combination of gemcitabine and treosulfan has demonstrated some efficacy in metastatic disease. We conducted a phase II trial to assess the second-line activity and toxicity of bendamustine hydrochloride, a nucleoside analogue with alkylating activity. Inclusion criteria were a Karnofsky performance status of > or = 60% and progressive disease during or after first-line chemotherapy. Bendamustine was administered at a dose of 120 mg/m2 on days 1 and 2. Cycles were repeated on day 22. The primary endpoint of the study was the determination of the number of patients achieving an objective response or stable disease. The secondary endpoint was toxicity. Eleven patients were enrolled into the trial. Grade III and IV toxicity consisted of anaemia, thrombocytopenia and leucocytopenia in two, one and two patients, respectively. No grade III or IV non-haematological toxicity was observed. According to Response Evaluation Criteria in Solid Tumours (RECIST), all patients showed progressive disease. We conclude that bendamustine is ineffective as second-line chemotherapy for metastatic uveal melanoma.

Adult↗
PubMed2005

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 non-Hodgkin'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.

Aged↗
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↗
PubMed2005

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 randomised phase III trial (OSHO# 19).

PURPOSE: The purpose of this study was to compare the efficacy and toxicity of bendamustine, vincristine + prednisone (BOP) with a standard regimen of cyclophosphamide, vincristine + prednisone (COP) in patients with previously untreated advanced indolent non-Hodgkin's lymphoma (NHL) and mantle cell lymphoma. METHODS: A total of 164 patients with follicular lymphoma (grade 1/2), mantle cell lymphoma or lymphoplasmacytic lymphoma (immunocytoma) was randomised to treatment with vincristine 2 mg (day 1) and prednisone 100 mg/m2 (days 1-5) + bendamustine 60 mg/m2 (days 1-5) or + cyclophosphamide 400 mg/m2 (days 1-5) for a total of eight 21-day cycles. RESULTS: The rate of complete remission was 22% with BOP and 20% with COP. The projected 5-year survival rate was 61% with BOP and 46% with COP. The BOP-associated 5-year survival advantage almost reached significance in the subgroup of patients who responded to therapy (74% vs. 56%; P = 0.05), and did reach significance in responders who did not receive interferon maintenance therapy (70% vs. 47%; P = 0.03). Toxicity was acceptable in both treatment groups, although alopecia and leucopenia were more severe with COP. CONCLUSIONS: Bendamustine can efficaciously and safely replace cyclophosphamide, as used in standard COP therapy, for the treatment of patients with indolent NHL and mantle cell lymphoma. Long-term survival data suggest a clinically significant benefit for patients treated with BOP.

Adult↗
PubMed2006

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.

Adult↗