Phase I trial of interleukin-2 and high-dose arginine butyrate in metastatic colorectal cancer

Douillard, Jean-Yves; Bennouna, Jaafar; Vavasseur, Fabienne; Deporte-Fety, R.; Thomare, P.; Giacalone, F.; Méflah, Khaled

doi:10.1007/s002620050026

Cited by 28 publications

(18 citation statements)

References 7 publications

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“…Phenylbutyrate was one of the first HDIs to be tested in patients. A related compound of sodium phenylbutyrate, arginine butyrate, was recently evaluated in a phase I trial on metastatic colorectal cancers in combination with interleukin-2, but induced severe liver damage (51). A combination of phenylbutyrate and all-trans retinoic acid (ATRA), for example, induced histone hyperacetylation and complete remission in a case of highly resistant promyelocytic leukemia before relapse occurred after 7 months (46,52).…”

Section: Valproic Acid -------------------------------------------------mentioning

confidence: 99%

Histone deacetylase inhibitors: A novel target of anticancer therapy (Review)

Kouraklis¹,

Theocharis²

2006

Oncol Rep

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Abstract. Accumulating evidence suggests that the acetylation and deacetylation of histones play significant roles in transcriptional regulation of eukaryotic cells. The balance between acetylation and deacetylation is an important factor in regulating gene expression and is thus linked to the control of cell fate. The histone deacetylase inhibitors (HDIs) including the hydroxamic acids, such as suberoylanilide hydroxamic acid and pyroxamide, the benzamides MS-275 and CI-994 and the butyrate derivative 4-PBA are a new class of anti-neoplastic agents currently being evaluated in clinical trials. Moreover, new synthetic HDIs have been used recently in phase I and II clinical trials. Over the next few years experts believe that as first generation HDIs produce clinical benefits and second generation inhibitors are rationally designed with improved specificity, this class of drugs will emerge as a new way of cancer treatment. The first clinical studies have shown that histone hyperacetylation can be achieved safely in humans and that treatment of cancer with such agents seems to become possible. The use of HDIs, probably in association with classical chemotherapy drugs or in combination with DNA-demethylating agents, could be promising for cancer patients. Further evaluation is needed to establish the clinical activity of combination therapy using HDIs with cytotoxic drugs or differentiation induced agents.

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Section: Valproic Acid -------------------------------------------------mentioning

confidence: 99%

Histone deacetylase inhibitors: A novel target of anticancer therapy (Review)

Kouraklis¹,

Theocharis²

2006

Oncol Rep

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“…The latter has a pleiotropic spectrum of action [100] and exerts only a weak repression of deacetylase activity, but has recently been used successfully in a combination therapy of promonocytic leukemia (PML). A related compound, arginine butyrate, was recently evaluated in a phase I trial on metastatic colorectal cancers in combination with interleukin-2, but induced severe liver damage [101]. Butyrate and its analogs are also currently being evaluated as differentiating agents in prostrate cancers.…”

Section: Current Treatment Strategiesmentioning

confidence: 99%

Histone acetylation and disease

Timmermann

Lehrmann

Polesskaya

et al. 2001

CMLS, Cell. Mol. Life Sci.

313

192

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Differential acetylation of histones and transcription factors plays an important regulatory role in developmental processes, proliferation and differentiation. Aberrant acetylation or deacetylation leads to such diverse disorders as leukemia, epithelial cancers, fragile X syndrome and Rubinstein-Taybi syndrome. The various groups of histone acetyltransferases (CBP/p300, GNAT, MYST, nuclear receptor coactivators and TAFII250) and histone deacetylases are surveyed with regard to their possible or known involvement in cancer progression and human developmental disorders. Current treatment strategies are discussed, which are still mostly limited to histone deacetylase inhibitors such as trichostatin A and butyrate.

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“…Sodium butyrate, a short-chain fatty acid (SCFA) produced during the fermentation of dietary fiber by endogenous intestinal bacteria, is currently being evaluated as an anti-neoplastic therapeutic agent [13], and clinical trials of BuA and its derivatives in cancer patients have already been initiated [14,15]. The inhibitory role of BuA against tumor growth is mediated through a direct effect on tumor cells that results in cell cycle arrest, differentiation, or apoptosis [16][17][18][19].…”

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confidence: 99%