Treatment of advanced cutaneous T-cell lymphomas with non-pegylated liposomal doxorubicin - Consensus of the lymphoma group of the Working Group Dermatologic Oncology.

Jan 2013

Assaf C, Becker JC, Beyer M, Cozzio A, Dippel E, Klemke CD, Kurschat P, Weichenthal M, Stadler R.

Source

Department of Dermatlogy, Helios Clinic Krefeld, Germany Department of Dermatology and Venereology, University of Graz, Austria Department of Dermatolgogy, Venereology and Allergology, Charité- University Medicine Berlin, Germany Department of Dermatology, University Clinic Zurich, Switzerland Department of Dermatolgoy, Municipal Clinic Ludwigshaven, Germany Department of Dermatology, University of Mannheim, Germany Department of Dermatology and Venereology, University of Cologne, Germany Department of Dermatology, University of Kiel, Germany Department of Dermatolgy, Johannes Wesling Clinic Minden, Germany.

Abstract

Background: Systemic treatment with pegylated liposomal doxorubicin is an established second-line treatment of advancedcutaneous T-cell lymphoma. Pegylated liposomal doxorubicin (PLD) is currently unavailable, therefore, clinical studies investigating the efficacy of non-pegylated liposomal formula (NPLD) have been analyzed. 

Methods: Since clinical trials comparing PLD and NPLD in CTCL do not exist, the clinical use of NPLD including safety and efficiency profile in other types of non-Hodgkin lymphoma were analyzed. 

Results: Clinical trials show a comparable efficacy of NPLD and PLD in non-Hodgkin lymphoma. The dosage of NPLD used in the treatment of systemic lymphoma within polychemotherapy regimens was 50 mg/m(2) every three weeks. Overall response was 75-95 %, including a complete remission rate of 65-80 % and 2- and 3-year overall survival rates of 55-75 %. These data indicate that the non-pegylated formula of doxorubicin has a similar antitumor effect as the pegylated one but shows reduced cardiotoxicity. The palmoplantar erythrodysesthesia frequently observed in PLD has not been observed with the use of the NPLD. 

Conclusions: The clinical use of NPLD in the treatment of CTCL is reasonable. In analogy to the clinical trials of NPLD in non-Hodgkin lymphoma a dosage of 50 mg/m(2) every three weeks is recommended for the treatment of CTCL.

Wiley Online

Advanced/aggressive CTCL: improving the efficacy of treatment.

Dec 2012

Zinzani PL.

Source

"L. e A. Seràgnoli" Institute of Hematology, University of Bologna, Bologna, Italy.

Abstract

Treatment regimens of patients with cutaneous T-cell lymphoma (CTCL) vary widely based on clinician preference and patient tolerance. Skin directed therapies are recommended for patients with early stage IA and IB MF, with combinations used in refractory cases. While no regimen has been proven to prolong survival in advanced stages, immunomodulatory regimens should be used initially to reduce the need for cytotoxic therapies. In more advanced stages of disease, treatment efforts should strive for palliation and improvement of quality of life. With many new therapies and strategies on the horizon, the future looks promising for CTCL patients.

PubMedC

Cutaneous peripheral T-cell lymphomas, unspecified/NOS and rare subtypes: a heterogeneous group of challenging cutaneous lymphomas.

Dec 2012

Kempf W, Rozati S, Kerl K, French LE, Dummer R.

Source

Department of Dermatology, University Hospital Zürich, Zürich, Switzerland - werner.kempf@access.unizh.ch.

Abstract

Cutaneous peripheral T-cell lymphoma, unspecified/not otherwise specified (PTL NOS) represents a phenotypically and prognostically heterogenous group of cutaneous T-cell lymphomas (CTCL) that do not fit into any of well defined defined CTCL subtypes. In the WHO-EORTC classification as well as the WHO classification, three entities have been delineated as provisional rare subtypes of PTL based on their characteristic clinico-pathological, immunophenotypic and prognostic features and have been separated out from PTL, NOS: Primary cutaneous CD4-positive small/medium T-cell lymphoma(CD4+ SMTL), primary cutaneous CD8-positive aggressive epidermotropic T-cell lymphoma (CD8+ AECTCL), and primarycutaneous gamma/delta T-cell lymphoma (CGD-TCL). CD4+ SMTL manifests in most patients with a solitary nodule in the head and neck area and nodular infiltrates of CD4+ small to medium-sized lymphocytes with nuclear pleomorphism. The prognosis of this lymphoproliferation is excellent in patients with a solitary lesion, but may be impaired in patients with multifocal disease. Rapidly evolving erosive or necrotic plaques and nodules with an epidermotropic infiltrate of CD8+ atypical lymphocytes are the hallmark of CD8+ AECTCL, which exhibits a poor prognosis. CGD-TCL displays a broad spectrum of clinical and histological manifestations with expression of the T-cell receptor gamma/delta chain as the common denominator and diagnostic marker. As most of other forms of PTL, CGD-TCL carries a poor prognosis. Despite the rarity of PTL NOS, clinicians as well as dermatopathologists and pathologists should be familiar with these rare CTC, especially since most of these lymphomas exhibit an unfavourable prognosis. Immediate intense treatment with multiagent chemotherapy and hematopoietic stem cell transplantation is indicated in patients with PTL NOS. This review focuses on the clinicopathological aspects, the diagnostic criteria and the classification of the rare subtypes of PTL and PTL NOS.

PubMed

Cutaneous T-Cell Lymphomas: A Review of New Discoveries and Treatments.

Feb 2012

Bloom T, Kuzel TM, Querfeld C, Guitart J, Rosen ST.

Source

Rush Medical College, 600 S. Paulina Street, Chicago, IL, 60612, USA, tara_a_bloom@rush.edu.

Abstract

OPINION STATEMENT:

Treatment regimens of patients with CTCL vary widely based on clinician preference and patient tolerance. Skin directed therapies are recommended for patients with early stage IA and IB MF, with combinations used in refractory cases. While no regimen has been proven to prolong survival in advanced stages, immunomodulatory regimens should be used initially to reduce the need for cytotoxic therapies. In more advanced stages of disease, treatment efforts should strive for palliation and improvement of quality of life. With many new therapies and strategies on the horizon, the future looks promising for CTCL patients. Unfortunately, other than allogeneic HCT, there are no potential curative therapies for CTCL. Clinical trials are currently underway to identify new therapies to improve quality of life for patients, and researchers are hard at work to identify novel pathways and genes for prognostication and as targets for therapies. Importantly, collaborative clinical trials to enhance rates of accrual need to be conducted, and improved interpretation of data via standardizing end points and response criteria should be an emphasis. Recently, the International Society for CutaneousLymphomas (ISCL), the United States Cutaneous Lymphoma Consortium (USCLC), and the Cutaneous Lymphoma Task Force of the European Organisation for Research and Treatment of Cancer (EORTC) met to develop consensus guidelines to facilitate collaboration on clinical trials. These proposed guidelines consist of: recommendations for standardizing general protocol design; a scoring system for assessing tumor burden in skin, lymph nodes, blood, and viscera; definition of response in skin, nodes, blood, and viscera; a composite global response score; and a definition of end points. Although these guidelines were generated by consensus panels, they have not been prospectively or retrospectively validated through analysis of large patient cohorts.

PubMed

Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

Denileukin diftitox for the treatment of cutaneous T-cell lymphoma

Biologics. 2008 Dec

Kaminetzky D, Hymes KB.
Division of Hematology/Oncology, New York University School of Medicine, New York, USA.

Cutaneous T-cell lymphoma/mycosis fungoides (CTCL/MF) is a rare lymphoproliferative disorder which can present as an indolent or as an aggressive process involving skin, lymph nodes, and blood. In stages IA, IB and IIA, it is usually managed with topical medications and phototherapy. If there is progression despite application of these treatments, or if the patient presents with a higher stage of disease, systemic chemotherapy or retinoids, rexinoids, biologic response modifiers are often necessary. Consequently, patients are often treated with a sequence of modalities and drugs. Denileukin diftitox (DD, Ontak(R)) is a targeted immunotoxin which has biological activity against malignancies expressing the IL-2 receptor. In addition to its unique mechanism of action, DD has a toxicity profile which does not overlap with most commonly used chemotherapeutic agents. CTCL/MF has been found be particularly susceptible to treatment with this agent. This review will describe the development DD, its proposed mechanism of action, the clinical trials which identified its utility in the treatment of CTCL/MF, the common toxicities encountered with this agent, and the management of these toxicities. In addition the incorporation of DD in the sequential treatment of CTCL/MF and data suggesting potential combination therapies employing this novel agent will be discussed.

Full text article:

DovePress