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

Strumberg, Dirk; Harstrick, A.; Doll, Kathia; Hoffmann, Britta; Seeber, S.

doi:10.1097/00001813-199606000-00007

Cited by 141 publications

(131 citation statements)

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“…This suggests a different mode of action, which was recently confirmed when gene expression profiling analysis identified a different gene profile activated by BM Niemeyer et al, 2004). It offers an explanation for the lack of cross-resistance with other alkylating agents, as observed in anthracycline-resistant breast cancer cell lines and cisplatinresistant ovarian cancer cell lines (Strumberg et al, 1996). Treatment with BM also induces a concentration-dependent apoptosis as evidenced by changes in Bcl-2 and Bax expression profiles in chronic B-cell lymphocytic leukaemia (Konstantinov et al, 2002;Schwänen et al, 2002).…”

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confidence: 99%

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

et al. 2007

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The aim of the study was to determine the maximum tolerated dose (MTD), the dose limiting toxicity (DLT), and the pharmacokinetic profile (P k ) of bendamustine (BM) on a day 1 and 2 every 3 weeks schedule and to recommend a safe phase II dose for further testing. Patients with solid tumours beyond standard therapy were eligible. A 30-min intravenous infusion of BM was administered d1 þ d2 q 3 weeks. The starting dose was 120 mg m À2 per day and dose increments of 20 mg m À2 were used. Plasma and urine samples were analysed using validated high-performance liquid chromatography/fluorescence assays. Fifteen patients were enrolled. They received a median of two cycles (range 1 -8). The MTD was reached at the fourth dose level. Thrombocytopaenia (grade 4) was dose limiting in two of three patients at 180 mg m À2 . One patient also experienced febrile neutropaenia. Lymphocytopaenia (grade 4) was present in every patient. Nonhaematologic toxicity including cardiac toxicity was not dose limiting with this schedule. Mean plasma P k values of BM were t max 35 min, t 1/2 49.1 min, V d 18.3 l m À2 , and clearance 265 ml min À1 m À2 . The mean total amount of BM and its metabolites recovered in the first micturition was 8.3% (range 2.7 -26%). The MTD of BM in the present dose schedule was 180 mg m À2 on day 1 þ 2. Thrombocytopaenia was dose limiting. The recommended dose for future phase II trials with this schedule is 160 mg m À2 per day.

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

et al. 2007

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“…Given the dual features, bendamustine exhibits only partial cross-resistance to other alkylating agents. 10 Its mechanisms of action include inhibition of mitotic checkpoints, enhancement of apoptosis, induction of mitotic catastrophe, and activation of DNA damage stress response and base excision DNA repair mechanisms.…”

Section: Pharmacologymentioning

confidence: 99%

The expanding role of bendamustine in chronic lymphocytic leukemia

Nair¹,

Ujjani²

2015

BLCTT

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Abstract:As the most prevalent form of adult leukemia, chronic lymphocytic leukemia (CLL) affects thousands of patients each year. Given the indolent nature of the disease, symptomatic patients frequently experience multiple relapses throughout their clinical course. Better therapeutic options are needed, particularly for the elderly population that characterizes the majority of affected patients. Bendamustine, a hybrid alkylating agent, has demonstrated remarkable activity in CLL in conjunction with a tolerable safety profile. Although historically used in relapsed and refractory disease, it has recently gained a role in the front-line setting, including younger, physically fit patients. Current investigatory efforts are focused on exploring the combination of bendamustine with novel therapies in CLL.

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“…Bendamustine, originally designed to have both alkylating 1) and antimetabolite properties, 2) has shown clinical activity against various human malignancies including non-Hodgkin's lymphoma [3][4][5][6][7] and chronic lymphocytic leukemia. 8) According to the National Comprehensive Cancer Network (NCCN) guidelines for patients with non-Hodgkin's lymphoma, 9) bendamustine alone or bendamustine with rituximab is used for patients with follicular lymphoma or mantle cell lymphoma.…”

Section: Decrease In Venous Irritation By Adjusting the Concentrationmentioning

confidence: 99%

Decrease in Venous Irritation by Adjusting the Concentration of Injected Bendamustine

Watanabe

Ikesue

Tsujikawa

et al. 2013

Biological & Pharmaceutical Bulletin

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Intravenous injection of bendamustine often causes venous irritation and also deteriorates the patient's quality of life. Thus, we evaluated the risk factors associated with venous irritation induced by bendamustine in patients with follicular lymphoma or mantle cell lymphoma. We also evaluated the effectiveness of intervention of changing the preparation procedure for bendamustine. All data were retrospectively collected from the electronic medical record system. In the initial analysis of the total 43 courses of bendamustine therapy, most patients (88%) were administered bendamustine with 250 mL of diluent according to the bendamustine package insert in Japan. The median concentration of bendamustine solution (0.56 mg/ mL vs. 0.24 mg/mL) and the incidences of venous irritation (66% vs. 0%, p=0.01) were significantly different between the patients receiving bendamustine at 250 mL and 500 mL of diluent. Based on this result, we proposed changing the final volume of bendamustine dissolution from 250 to 500 mL, which is recommended in other countries. After this intervention, the incidence of venous irritation was significantly reduced from 58 to 20% (p=0.02). The incidence of venous irritation increased in a concentration-dependent manner (≤0.40 mg/mL: 6%; 0.41-0.60 mg/mL: 62%, p<0.001; >0.60 mg/mL: 75%, p<0.001). We conclude that a high concentration bendamustine solution is a risk factor for venous irritation and that 500 mL of diluent is ideal. To further reduce the incidence of venous irritation, the concentration of bendamustine solution is recommended to be 0.40 mg/mL or less.

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

Cited by 141 publications

References 0 publications

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

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

The expanding role of bendamustine in chronic lymphocytic leukemia

Decrease in Venous Irritation by Adjusting the Concentration of Injected Bendamustine

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