A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma

Foss, Francine M.; DiVenuti, Gina

doi:10.1182/blood-2004-11-4570

Cited by 103 publications

(40 citation statements)

References 9 publications

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“…Interestingly, the retinoid X receptor retinoid, bexarotene, a new therapeutic agent for mycosis fungoides (34), up-regulates both the p55 and p75 subunits of IL-2R. This, in turn, enhances the susceptibility of the malignant cells to denileukin diftitox, resulting in overall response rates of 67% in relapsed CTCL patients (35).…”

Section: Discussionmentioning

confidence: 99%

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Hahtola

Tuomela

Elo

et al. 2006

Clinical Cancer Research

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Purpose: Increased production of Th2 cytokines characterizes Sezary syndrome, the leukemic form of cutaneous T-cell lymphomas (CTCL). To identify the molecular background and to study whether shared by the most common CTCL subtype, mycosis fungoides, we analyzed the gene expression profiles in both subtypes. Experimental Design: Freshly isolated cells from 30 samples, representing skin, blood, and enriched CD4+ cell populations of mycosis fungoides and Sezary syndrome, were analyzed with Affymetrix (Santa Clara, CA) oligonucleotide microarrays, quantitative PCR, or immunohistochemistry. The gene expression profiles were combined with findings of comparative genomic hybridization of the same samples to identify chromosomal changes affecting the aberrant gene expression. Results: We identified a set of Th1-specific genes [e.g., TBX21 (T-bet), NKG7, and SCYA5 (RANTES)] to be down-regulated in Sezary syndrome as well as in a proportion of mycosis fungoides samples. In both Sezary syndrome and mycosis fungoides blood samples, the S100P and LIR9 gene expression was up-regulated. In lesional skin, IL7R and CD52 were up-regulated. Integration of comparative genomic hybridization and transcriptomic data identified chromosome arms 1q, 3p, 3q, 4q, 12q, 16p, and 16q as likely targets for new CTCL-associated gene aberrations. Conclusions: Our findings revealed several new genes involved in CTCL pathogenesis and potential therapeutic targets. Down-regulation of a set of genes involved in Th1 polarization, including the major Th1-polarizing factor, TBX21, was for the first time associated with CTCL. In addition, a plausible explanation for the proliferative response of CTCL cells to locally produced interleukin-7 was revealed.

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Section: Discussionmentioning

confidence: 99%

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Hahtola

Tuomela

Elo

et al. 2006

Clinical Cancer Research

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“…Bexarotene combined with denileukin diftitox provides a noteworthy example, as bexarotene was shown to increase IL-2Rb (CD122) expression in malignant T cells [232], conferring increased sensitivity to denileukin diftitox, thus forming the rationale for a phase I study combining these two agents [233]. In this study, 14 patients with relapsed/refractory CTCL received bexarotene (75-300 mg daily) with denileukin diftitox (18 mcg/kg daily for 3 days every 21 days).…”

Section: Bexarotenementioning

confidence: 99%

“…In this study, 14 patients with relapsed/refractory CTCL received bexarotene (75-300 mg daily) with denileukin diftitox (18 mcg/kg daily for 3 days every 21 days). Eight responses, including four complete responses, and upregulation of the IL-2 receptor following therapy were observed [233]. Future studies clarifying the optimal use of bexarotene, either in combination or sequentially with other agents, are needed.…”

Section: Bexarotenementioning

confidence: 99%

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Wilcox

2011

American J Hematol

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Disease overview: Cutaneous T‐cell lymphomas are a heterogenous group of T‐cell lymphoproliferative disorders involving the skin, the majority of which may be classified as Mycosis fungoides (MF) or Sézary syndrome (SS).Diagnosis: The diagnosis of MF or SS requires the integration of clinical and histopathologic data.Risk‐adapted therapy: Tumor, node, metastasis, and blood (TNMB) staging remains the most important prognostic factor in MF/SS and forms the basis for a “risk‐adapted,” multidisciplinary approach to treatment. For patients with disease limited to the skin, expectant management or skin‐directed therapies is preferred, as both disease‐specific and overall survival for these patients is favorable. In contrast, patients with advanced‐stage disease with significant nodal, visceral, or blood involvement are generally approached with biologic‐response modifiers, denileukin diftitox, and histone deacetylase inhibitors before escalating therapy to include systemic, single‐agent chemotherapy. Multiagent chemotherapy may be used for those patients with extensive visceral involvement requiring rapid disease control. In highly‐selected patients with disease refractory to standard treatments, allogeneic stem‐cell transplantation may be considered. Am. J. Hematol., 2011. © 2011 Wiley‐Liss, Inc.

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“…187 Fourteen patients with relapsed or refractory CTCL were treated with escalating doses of bexarotene (75-300 mg/d) and denileukin diftitox (18 mcg/kg/ d ϫ3 days every 21 days) had an overall response of 67% (4 complete responses, 4 partial responses). 187 The results of a multicenter phase III double-blind randomized trial of denileukin diftitox, recently published, showed significant response rates at both 9 and 18 mcg/kg dose levels compared with placebo controls in patients who had received Յ3 prior therapies. 188 Unfortunately, because of manufacturing issues, denileukin diftitoxin has been unavailable since fall 2011.…”

Section: Denileukin Diftitoxmentioning

confidence: 99%

Choosing a systemic treatment for advanced stage cutaneous T-cell lymphoma: mycosis fungoides and Sézary syndrome

Duvic

2015

Hematology

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A phase-1 trial of bexarotene and denileukin diftitox in patients with relapsed or refractory cutaneous T-cell lymphoma

Cited by 103 publications

References 9 publications

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Th1 Response and Cytotoxicity Genes Are Down-Regulated in Cutaneous T-Cell Lymphoma

Cutaneous T‐cell lymphoma: 2011 update on diagnosis, risk‐stratification, and management

Choosing a systemic treatment for advanced stage cutaneous T-cell lymphoma: mycosis fungoides and Sézary syndrome

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