RESUMO
BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.
Assuntos
Bexaroteno , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Tetra-Hidronaftalenos , Humanos , Bexaroteno/uso terapêutico , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Tetra-Hidronaftalenos/uso terapêutico , Tetra-Hidronaftalenos/efeitos adversos , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Espanha , Linfoma Cutâneo de Células T/tratamento farmacológico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND AND OBJECTIVES: Bexarotene has been approved to treat advanced stage cutaneous T-cell lymphomas (CTCL) since 1999. However, very few data have been published on its long-term safety and efficacy profile. The aim of this study is to determine the tolerability to bexarotene and outcomes by collecting the 2nd largest case series to date on its long-term use vs CTCL. MATERIAL AND METHOD: This was a multicenter retrospective review of 216 patients with mycosis fungoides (174), or Sézary syndrome (42) on a 10-year course of bexarotene alone or in combination with other therapies at 19 tertiary referral teaching hospitals. RESULTS: A total of 133 men (62%) and 83 women (38%) were included, with a mean age of 63.5 year (27-95). A total of 45% were on bexarotene monotherapy for the entire study period, 22% started on bexarotene but eventually received an additional therapy, 13% were on another treatment but eventually received bexarotene while the remaining 20% received a combination therapy since the beginning. The median course of treatment was 20.78 months (1-114); and the overall response rate, 70.3%. Complete and partial response rates were achieved in 26% and 45% of the patients, respectively. Treatment was well tolerated, being the most common toxicities hypertriglyceridemia (79%), hypercholesterolemia (71%), and hypothyroidism (52%). No treatment-related grade 5 adverse events were reported. CONCLUSIONS: Our study confirms bexarotene is a safe and effective therapy for the long-term treatment of CTCL.
Assuntos
Bexaroteno , Micose Fungoide , Síndrome de Sézary , Neoplasias Cutâneas , Tetra-Hidronaftalenos , Humanos , Bexaroteno/uso terapêutico , Masculino , Feminino , Idoso , Estudos Retrospectivos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias Cutâneas/tratamento farmacológico , Adulto , Tetra-Hidronaftalenos/uso terapêutico , Tetra-Hidronaftalenos/efeitos adversos , Micose Fungoide/tratamento farmacológico , Síndrome de Sézary/tratamento farmacológico , Espanha , Linfoma Cutâneo de Células T/tratamento farmacológico , Resultado do Tratamento , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversosRESUMO
BACKGROUND: Data regarding response to treatment in lymphomatoid papulosis (LyP) are scarce. AIM: To assess the daily clinical practice approach to LyP and the response to first-line treatments. METHODS: This was a retrospective study enrolling 252 patients with LyP. RESULTS: Topical steroids, methotrexate and phototherapy were the most common first-line treatments, prescribed for 35%, 20% and 14% of the patients, respectively. Complete response (CR) was achieved in 48% of treated patients. Eczematous lesions significantly increased relative risk (RR) of not achieving CR (RR = 1.76; 95% CI 1.16-2.11). Overall median time to CR was 10 months (95% CI 6-13 months), and 78% of complete responders showed cutaneous relapse; both results were similar for all treatment groups (P > 0.05). Overall estimated median disease-free survival (DFS) was 11 months (95% CI 9-13 months) but DFS for patients treated with phototherapy was 23 months (95% CI 10-36 months; P < 0.03). Having the Type A LyP variant (RR = 2.04; 95% CI 0.96-4.30) and receiving a first-line treatment other than phototherapy (RR = 5.33; 95% CI 0.84-33.89) were significantly associated with cutaneous early relapse. Of the 252 patients, 31 (13%) had associated mycosis fungoides unrelated to therapeutic approach, type of LyP or T-cell receptor clonality. CONCLUSIONS: Current epidemiological, clinical and pathological data support previous results. Topical steroids, phototherapy and methotrexate are the most frequently prescribed first-line treatments. Although CR and cutaneous relapse rates do not differ between them, phototherapy achieves a longer DFS. Presence of Type A LyP and use of topical steroid or methotrexate were associated with an increased risk of early relapse.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Papulose Linfomatoide/tratamento farmacológico , Metotrexato/uso terapêutico , Fototerapia , Neoplasias Cutâneas/tratamento farmacológico , Esteroides/uso terapêutico , Administração Tópica , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Intervalo Livre de Doença , Feminino , Humanos , Lactente , Papulose Linfomatoide/mortalidade , Papulose Linfomatoide/terapia , Masculino , Pessoa de Meia-Idade , Micose Fungoide/mortalidade , Neoplasias Primárias Múltiplas , Receptores de Antígenos de Linfócitos T , Estudos Retrospectivos , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/terapia , Adulto JovemAssuntos
Inibidor p16 de Quinase Dependente de Ciclina/genética , Citarabina/efeitos adversos , Doenças do Cabelo/induzido quimicamente , Proteínas Hedgehog/metabolismo , Ceratose/induzido quimicamente , Idoso , Biópsia , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Doenças do Cabelo/diagnóstico , Doenças do Cabelo/metabolismo , Folículo Piloso/patologia , Proteínas Hedgehog/efeitos dos fármacos , Humanos , Imunossupressores/efeitos adversos , Ceratose/diagnóstico , Ceratose/metabolismo , Masculino , Pele/patologiaRESUMO
INTRODUCTION: Cell adhesion molecules play a pivotal role in the establishment of T-cell populations in the skin. In this study, we quantify the expression of cell adhesion molecules in patients with cutaneous T-cell lymphoma (CTCL) and compare it with the expression found in other skin diseases. MATERIAL AND METHODS: Frozen material was obtained from 42 patients in 5 different groups: early CTCL, comprising patients with patch- and plaque-stage of mycosis fungoides (n=11); advanced CTCL (n=7), comprising patients with mycosis fungoides (n=3) and Sézary syndrome (n=4); inflammatory skin disease (n=12), comprising patients with psoriasis (n=9) and atopic dermatitis (n=3); chronic skin diseases with persistent plaques that do not fulfil the histological criteria for mycosis fungoides (pre-CTCL) (n=8); and healthy volunteers (n=4). Expression of the following cell adhesion molecules was analyzed: lymphocyte function-associated antigen 1, intercellular adhesion molecule 1 (ICAM-1), ICAM-3, cutaneous lymphocyte-associated antigen, E-selectin, very late antigen 4, vascular cell adhesion molecule 1, alphaEbeta7 integrin, and E-cadherin. RESULTS: The immunohistochemical analyses used here revealed statistically significant differences between CTCL and other skin diseases but not between early and advanced CTCL. The expression of alphaEbeta7 integrin and ICAM-3 in the epidermis per high-power field (400× magnification) allowed the different groups to be distinguished from each other, except for advanced CTCL and pre-CTCL. There were statistically significant differences between advanced CTCL and pre-CTCL in terms of the expression of E-selectin at 400× magnification and the expression of ICAM-1 in a honeycomb pattern in epidermal keratinocytes. CONCLUSIONS: The expression of cell adhesion molecules involved in the adhesion and migration of lymphocytes in the skin does not differ significantly between initial and advanced stages of CTCL.