Randomized Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen Sodium (Bcl-2 antisense) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

O’Brien, Susan; Moore, Joseph O.; Boyd, Thomas E.; Larratt, Loree; Skotnicki, Aleksander B.; Koziner, Benjamín; Chanan‐Khan, Asher; Seymour, John F.; Bociek, R. Gregory; Pavletić, S.Ž.; Kanti, R.

doi:10.1200/jco.2006.07.1191

Cited by 265 publications

(152 citation statements)

References 32 publications

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“…aiming at cancer treatment. The G3139 ODN has been one of the most relevant BCL2-silencing molecules tested, as illustrated by the promising results achieved in several clinical trials, notably in phase III trials against melanoma and chronic lymphocytic leukemia (12,13). Another phase III trial (AGENDA trial) was recently initiated in patients with advanced melanoma.…”

Section: Discussionmentioning

confidence: 99%

In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

Santos

Pereira

Lima

et al. 2010

Braz J Med Biol Res

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Section: Discussionmentioning

confidence: 99%

In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

Santos

Pereira

Lima

et al. 2010

Braz J Med Biol Res

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“…Another strategy involves the use of an antisense oligonucleotide to target Bcl-2 mRNA (oblimersen sodium). The administration of this molecule in different combinatorial approaches (that is, with chemotherapy among others) showed activity for treatment of chronic lymphocytic leukemia and malignant melanoma in phase III clinical trials (Bedikian et al, 2006;O'Brien et al, 2007).…”

Section: Current Therapeutic Paradigms To Treat Cancermentioning

confidence: 99%

Towards novel paradigms for cancer therapy

et al. 2010

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Cancer is a complex progressive multistep disorder that results from the accumulation of genetic and epigenetic abnormalities, which lead to the transformation of normal cells into malignant derivatives. Despite enormous progress in the understanding of cancer biology including the decryption of multiple regulatory networks governing cell growth and death, and despite the possibility of analyzing (epi)genetic deregulation at the genome-wide scale, cancertargeted therapy is still the exception. In fact, to date there are still far too few examples of therapies leading to cure; treatment-derived toxicity is a major issue, and cancer remains to be one of the largest causes of death worldwide. The purpose of this review is to discuss the state of the art of cancer therapy with respect to the key issue of any treatment, namely its target selectivity. Therefore, we recapitulate and discuss current concepts and therapies targeting tumorspecific features, including oncofusion proteins, aberrant kinase activities and epigenetic tumor makeup. We analyze strategies designed to induce tumor-selective death such as the use of oncolytic virus, tumoricidal proteins (NS1, Eorf4, apoptin, HAMLET (human a-lactalbumin made lethal to tumor cells)) and activation of signaling pathways involved in tumor surveillance. We emphasize the potential of the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) pathway, an essential component of the evolutionary developed defense systems that eradicate malignant cells. Finally, we discuss the necessity of targeting tumor-initiating cells (TICs) to avoid relapse and increase the chances of complete remission, and describe emerging concepts that might provide novel avenues for cancer therapy.

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“…The five-year survival was significantly prolonged in patients who had achieved at least PR. Patients with fludarabine sensitive disease had most benefit [39].…”

Section: Oblimersenmentioning

confidence: 99%

Refractory chronic lymphocytic leukemia - new therapeutic strategies

Schnaiter

Stilgenbauer

2010

Oncotarget

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AbstrAct:Treatment outcome of chronic lymphocytic leukemia (CLL) has considerably improved since the introduction of fludarabine (F) as part of the standard therapy. Nevertheless, refractoriness to fludarabine occurs in a significant number of patients and is associated with an unfavorable prognosis. Important risk factors are 17p deletion and/or mutation of TP53. For this subgroup the CD52 antibody alemtuzumab (A) presents a new treatment approach and has already been approved. Meanwhile we have to face also refractoriness to alemtuzumab. Importantly, the monoclonal CD20 antibody ofatumumab has now shown efficacy in F and A double-refractory CLL. The next generation CD20 antibody GA-101 is currently compared to rituximab (R) and will possibly be its more potent successor. Further B-cell antigens are targeted by lumiliximab (CD23), TRU-016 (CD37) and blinatumomab (CD19). Apart from monoclonal antibody therapies, a great number of small molecules are examined for the treatment of refractory and relapsed CLL. Most of these agents aim to overcome apoptosis resistance in CLL cells or influence the microenvironment. Typical targets are regulators of the cell cycle and antiapoptotic molecules like the members of the Bcl-2 family. Up to now the most promising agents appear to be flavopiridol and lenalidomide among others.

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Randomized Phase III Trial of Fludarabine Plus Cyclophosphamide With or Without Oblimersen Sodium (Bcl-2 antisense) in Patients With Relapsed or Refractory Chronic Lymphocytic Leukemia

Abstract: The addition of oblimersen to fludarabine plus cyclophosphamide significantly increases the CR/nPR rate in patients with relapsed or refractory CLL (particularly fludarabine-sensitive patients), as well as response duration among patients who achieve CR/nPR.

Cited by 265 publications

References 32 publications

In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

In vitro modulation of Bcl-2 levels in small cell lung cancer cells: effects on cell viability

Towards novel paradigms for cancer therapy

Refractory chronic lymphocytic leukemia - new therapeutic strategies

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