Bendamustine: something old, something new

@article{Tageja2010BendamustineSO,
  title={Bendamustine: something old, something new},
  author={Nishant Tageja and Jasdeepa Nagi},
  journal={Cancer Chemotherapy and Pharmacology},
  year={2010},
  volume={66},
  pages={413-423}
}
BackgroundBendamustine (Treanda, Ribomustin) is a water-soluble, bifunctional chemotherapeutic agent that also has potential antimetabolite properties and only partial cross-resistance with other alkylators. Designed in 1963 and re-discovered in 1990s, this drug’s unique mechanism of action and favorable side-effect profile promise a major role in the management of lymphoproliferative disorders. Bendamustine has been designated as an orphan drug in the United States, conferring prolonged market… 
Bendamustine: Safety and Efficacy in the Management of Indolent Non-Hodgkins Lymphoma
  • N. Tageja
  • Medicine
    Clinical Medicine Insights. Oncology
  • 2011
TLDR
Bendamustine plus rituximab is highly effective in patients with relapsed-refractory indolent lymphoma, inducing remissions in 90% or more and a median progression-free survival of 23–24 months.
Pharmacokinetic evaluation and therapeutic activity of bendamustine in B-cell lymphoid malignancies
TLDR
The chemical structure, mechanism of action, pharmacokinetic properties and clinical application of bendamustine in hematological malignancies are presented and its real place in the management of these diseases is established.
An old drug with a new future: bendamustine in multiple myeloma
TLDR
Bendamustine seems to be efficacious either in monotherapy or in combination with other drugs in previously treated or untreated patients, making it potentially more effective than other alkylating agents and has an acceptable toxicity profile and is suitable for patients with renal impairment.
Bendamustine in multiple myeloma
TLDR
Bendamustine is an old drug rediscovered in the last decade whose unique mechanism of action with structural similarities to both alkylating agents and antimetabolities has reawakened interest in the use of this drug in the treatment of multiple myeloma.
The combination effects of bendamustine with antimetabolites against childhood acute lymphoblastic leukemia cells
TLDR
In vitro activity of bendamustine combined with other antimetabolite drugs on B cell precursor acute lymphoblastic leukemia cell lines established from pediatric patients with refractory or relapsed ALL is investigated and may represent a promising combination for salvage treatment in childhood ALL.
Esters of Bendamustine Are by Far More Potent Cytotoxic Agents than the Parent Compound against Human Sarcoma and Carcinoma Cells
TLDR
Bendamustine esters proved to be considerably more potent cytotoxic agents than the parent compound against a broad panel of human cancer cell types, including hematologic and solid malignancies, which are resistant to bendamustines.
Bendamustine: a review of its use in the management of indolent non-Hodgkin's lymphoma and mantle cell lymphoma.
TLDR
Bendamustine is a unique alkylating agent, which in clinical trials has demonstrated consistent efficacy and acceptable tolerability in patients with indolent NHL or MCL.
Purine Analog-Like Properties of Bendamustine Underlie Rapid Activation of DNA Damage Response and Synergistic Effects with Pyrimidine Analogues in Lymphoid Malignancies
TLDR
Bendamustine increased the expression of ENT1 at both mRNA and protein levels and enhanced the uptake of Ara-C and subsequent increase in Ara-CTP in HBL-2 cells to an extent comparable with the purine analog fludarabine, which may underlie favorable combinations with other alkylators and pyrimidine analogues.
A retrospective study evaluating the efficacy and safety of bendamustine in the treatment of mantle cell lymphoma
TLDR
Bendamustine in combination with rituximab demonstrated a high response rate in this study of patients with predominantly relapsed MCL, and factors significantly associated with longer survival were achieving a CR and classical variant of MCL.
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References

SHOWING 1-10 OF 66 REFERENCES
Metabolism and mechanisms of action of bendamustine: rationales for combination therapies.
  • V. Gandhi
  • Chemistry, Biology
    Seminars in oncology
  • 2002
Bendamustine (Treanda) Displays a Distinct Pattern of Cytotoxicity and Unique Mechanistic Features Compared with Other Alkylating Agents
TLDR
It is suggested that bendamustine possesses mechanistic features that differentiate it from other alkylating agents and may contribute to its distinct clinical efficacy profile.
Bendamustine HCL for the treatment of relapsed indolent non-Hodgkin’s lymphoma
  • R. Weide
  • Medicine, Chemistry
    Therapeutics and clinical risk management
  • 2008
TLDR
Bendamustine is an alkylating agent which also shows properties of a purine analog which has been shown to be highly active in relapsed/refractory indolent lymphomas and mantle cell lymphomas achieving long lasting complete remissions.
Weekly treatment with a combination of bortezomib and bendamustine in relapsed or refractory indolent non-Hodgkin lymphoma
TLDR
Bendamustine and bortezomib are both active in the treatment of patients with indolent NHL and appear not to be cross-resistant with prior therapy, and a dose finding study using a combination of the two drugs was initiated.
Bendamustine Mitoxantrone and Rituximab (BMR): A New Effective Regimen for Refractory or Relapsed Indolent Lymphomas
TLDR
In conclusion, BMR is a well tolerated, very effective outpatient regimen of treatment for relapsed and refractory indolent lymphoid malignancies.
Repeated administration of short infusions of bendamustine: a phase I study in patients with advanced progressive solid tumours
TLDR
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.
Characterization of two phase I metabolites of bendamustine in human liver microsomes and in cancer patients treated with bendamustine hydrochloride
TLDR
It is indicated 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.
Bendamustine in patients with rituximab-refractory indolent and transformed non-Hodgkin's lymphoma: results from a phase II multicenter, single-agent study.
  • J. Friedberg, P. Cohen, B. Cheson
  • Medicine
    Journal of clinical oncology : official journal of the American Society of Clinical Oncology
  • 2008
TLDR
Single-agent bendamustine produced durable objective responses with acceptable toxicity in heavily pretreated patients with rituximab-refractory, indolent NHL and will serve as a benchmark for future clinical trials in this novel patient population.
SYNTHESIS AND CHARACTERIZATION OF SOME NEW PHASE II METABOLITES OF THE ALKYLATOR BENDAMUSTINE AND THEIR IDENTIFICATION IN HUMAN BILE, URINE, AND PLASMA FROM PATIENTS WITH CHOLANGIOCARCINOMA
TLDR
The identification of cysteine S-conjugates provide evidence that a major route of bendamustine metabolism in humans involves conjugation with glutathione, besides phase I metabolism and hydrolytic degradation, and require further investigation.
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