RESUMEN
BACKGROUND: Advanced-stage cutaneous T-cell lymphomas (CTCLs) are rare, usually refractory, and fatal diseases. Case series have suggested that allogeneic haematopoietic stem cell transplantation (HSCT) might improve the prognosis of advanced-stage CTCLs. The objective of this study was to investigate the effect of allogeneic HSCT compared with non-HSCT therapy on the outcome of individuals with advanced-stage CTCLs. METHODS: In this prospective, multicentre, matched controlled trial, conducted at 30 hospitals, participants with advanced CTCLs were allocated treatment: if they had an available compatible related donor they were assigned to allogeneic HSCT, or if not they were allocated to non-allogeneic HSCT therapy. Key inclusion criteria were participants aged 18-70 years, with advanced stage mycosis fungoides or Sézary syndrome, and at least one poor prognostic criteria. Participants were excluded if they were not in complete or partial remission of the disease. Propensity score 1:1 matching with replacement (ie, that each participant treated with HSCT was matched to the participant with the closest propensity score treated with non-HSCT therapy, even if they had already been matched) was used to handle confounding factors, with the balance of covariate distribution between HSCT and non-HSCT groups assessed using standardised mean differences. The primary endpoint was progression-free survival in the matched intention-to-treat population. This trial is registered with ClinicalTrials.gov (NCT02520908), and is currently active but not recruiting. FINDINGS: From June 1, 2016, to March 3, 2022, total of 99 participants were enrolled at 17 centres in France. Participants with a sibling or matched unrelated donor were assigned to allogeneic HSCT (HSCT group, n=55 [56%]) and participants without a donor were assigned to non-allogeneic HSCT treatment (non-HSCT group, n=44 [44%]). The median follow-up among survivors was 12·6 months (IQR 11·0-35·2). In the HSCT group, 51 participants (93%) were 1:1 matched to participants from the non-HSCT group. In the intention-to-treat analysis, median progression-free survival was significantly longer in the HSCT group (9·0 months [95% CI 6·6-30·5]) than in the non-HSCT group (3·0 months [2·0-6·3]), with a hazard ratio of 0·38 (95% CI 0·21-0·69; p<0·0001). In the per-protocol population, 40 participants (78%) in the HSCT group had 101 serious events and 29 participants (67%) in the non-HSCT group had 70 serious adverse events. The most common serious adverse event other than graft-versus-host disease in both groups was infections, occurring in 30 participants (59%) in the HSCT group and in 19 participants (44%) in the non-HSCT group. INTERPRETATION: Allogeneic HSCT was associated with significantly longer progression-free survival in participants with advanced-stage CTCLs. These results indicate that allogeneic HSCT treatment should be made available to individuals with high-risk, advanced-stage mycosis fungoides or Sézary syndrome who achieve pre-transplant disease remission. FUNDING: French Ministry of Health, National Cancer Institute, Programme Hospitalier de Recherche Clinique en Cancérologie.
Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T , Micosis Fungoide , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Estudios Prospectivos , Síndrome de Sézary/terapia , Síndrome de Sézary/etiología , Puntaje de Propensión , Linfoma Cutáneo de Células T/terapia , Linfoma Cutáneo de Células T/etiología , Trasplante Homólogo , Trasplante de Células Madre Hematopoyéticas/métodos , Micosis Fungoide/etiología , Micosis Fungoide/patología , Neoplasias Cutáneas/terapia , Neoplasias Cutáneas/etiologíaRESUMEN
BACKGROUND: Our objective was to describe the clinical, histological characteristics, and disease outcome of a cohort of mycosis fungoides (MF) diagnosed during childhood including disease status at adulthood. METHODS: This is a retrospective multicentre survey of patients aged under 18 years at diagnosis with histologically confirmed MF. Patients' clinical and histological characteristics, treatments, and disease outcome (for patients followed for more than 12 months) were analysed. RESULTS: Forty-six patients were included (median age at diagnosis: 11 years; M:F sex ratio: 3:1) with 39 (85%) followed for at least 12 months. Thirty-nine patients (85%) had stage I MF. Hypopigmented patches were observed in 48% and folliculotropism in 43% patients. Immunophenotype of the skin infiltrate was predominantly CD8+ in 17% of patients. Initial management included a wait-and-see strategy in 6/39 (15%), skin-directed treatment in 27 (69%), and systemic treatment in 6 (15%) patients, respectively, with partial or complete clinical response (PR or CR) observed in 28 patients (72%). 14/39 patients (36%) relapsed after initial response. After a median follow-up period of 54 months, disease status at last news was PR or CR in 31/39 (79%), stable disease in 6 (15%), and progression in 2 (5%) patients. Histological transformation was observed in 3/39 (8%). Of the 15 patients followed until adulthood, 13 (87%) had persistent MF. DISCUSSION: This survey confirms the high frequency of hypopigmented and folliculotropic lesions and of CD8+ immunophenotype compared to adult MF patients. The long-term course is usually indolent but transformation may occur sometimes long after disease onset and the disease may persist during adulthood.
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Hipopigmentación , Micosis Fungoide , Neoplasias Cutáneas , Adulto , Humanos , Niño , Adolescente , Anciano , Neoplasias Cutáneas/diagnóstico , Micosis Fungoide/diagnóstico , Estudios Retrospectivos , Hipopigmentación/tratamiento farmacológico , Hipopigmentación/patología , Administración CutáneaRESUMEN
Primary cutaneous diffuse large B-cell lymphoma, leg-type (PCDLBCL-LT) is an aggressive cutaneous lymphoma. Bone involvement is rare and poorly described. We present five cases of PCDLBCL-LT with bone localization. In four cases, the bone involvement was diagnosed during the initial staging with positron emission tomography (PET) or computed tomography (CT) scan, and in the fifth case after tibial fracture during treatment with rituximab (RTX) and polychemotherapy (PCT). PCDLBCL-LT can be asymptomatic and involve bone sites distant from cutaneous lesions. None had other extracutaneous involvement. In our series, all patients received RTX-PCT as first-line chemotherapy and all had early relapses or progression. Second-line treatments had poor efficacy. Our series shows that bone involvement seems to be associated with poor prognosis in PCDLBCL-LT. Bone localization is not diagnosed with initial thoracic-abdominal-pelvic CT when asymptomatic and affecting the limbs only. If there is a suspicion of PCDLBCL-LT, patients should undergo systematic investigation with alternative imaging techniques, including PET, both at baseline and if there is any concern during follow-up.
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Neoplasias Óseas , Linfoma de Células B Grandes Difuso , Neoplasias Cutáneas , Humanos , Pierna/patología , Linfoma de Células B Grandes Difuso/diagnóstico por imagen , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Extremidad Inferior/patología , Rituximab/uso terapéutico , Neoplasias Óseas/tratamiento farmacológico , Neoplasias Cutáneas/patologíaRESUMEN
Cutaneous involvement in Waldenström's macroglobulinaemia (WM) has been poorly characterized. To describe this involvement, a retrospective study of 19 patients with WM and cutaneous involvement of tumour B cells was performed. Twelve patients (group 1) had lymphoplasmacytic, non-transformed cutaneous proliferation, while in 7 cases (group 2) cutaneous involvement corresponded to histological transformation. In group 1, skin involvement was inaugural in 6 cases. The lesions were infiltrated plaques (83%), papules (25%) and tumours (42%). Four patients had a similar clinical picture (purplish, bilateral and symmetrical infiltration on the face). MYD88 L265P mutation was detected in the skin biopsy in all 6 cases tested. The 3-year specific survival rate was 88%. In group 2, cutaneous transformation occurred during the follow-up of the WM (71%). Lesions presented as ulcerated tumours (86%) of the trunk (57%) and lower limbs (57%). The 3-year specific survival rate was 22%. Skin involvement in WM has distinctive characteristics (e.g. clinical, histological, immunohistochemical, MYD88 L265P mutation).
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Macroglobulinemia de Waldenström , Humanos , Mutación , Factor 88 de Diferenciación Mieloide/genética , Estudios Retrospectivos , Piel , Macroglobulinemia de Waldenström/diagnóstico , Macroglobulinemia de Waldenström/genéticaRESUMEN
BACKGROUND: In Europe, contact photosensitivity to phenothiazines is well-known, particularly in southern countries. Topical phenothiazines are widely used and sold over-the-counter (OTC) for the treatment of mosquito bites and pruritus in France. OBJECTIVE: To report a series of cases with photodermatitis following use of topical phenothiazines. METHOD: A retrospective study of cases of contact dermatitis from phenothiazines seen in French photodermatology centers was performed. RESULTS: In all, 14 patients with a diagnosis of contact dermatitis from phenothiazines were included. These patients developed eczema on the application sites, and in 13 the eruption spread to photodistributed sites. Topical products containing isothipendyl were the most common cause of photodermatitis. One patient had photoaggravated eczema due to promethazine cream. All patients stopped using topical phenothiazines and were treated successfully with topical corticosteroids. One patient relapsed and developed persistent light eruption. In all of the nine cases tested, photopatch testing to the topical phenothiazine used "as is" was positive. Isothipendyl, chlorproethazine, and the excipients were not tested. Photopatch tests to chlorpromazine and promethazine were positive in 8 of 12 and 7 of 13 tested, respectively. CONCLUSION: Use of isothipendyl and promethazine as OTC (or even prescribed) drugs needs to be limited due to severe reactions and sensitization to other phenothiazines that consequently will have to be avoided.
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Dermatitis Fotoalérgica/etiología , Fenotiazinas/efectos adversos , Administración Cutánea , Adulto , Anciano , Anciano de 80 o más Años , Clorpromazina/efectos adversos , Clorpromazina/análogos & derivados , Femenino , Antagonistas de los Receptores Histamínicos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Prometazina/efectos adversos , Tiazinas/efectos adversosAsunto(s)
Anticuerpos Monoclonales Humanizados , Progresión de la Enfermedad , Síndrome de Sézary , Neoplasias Cutáneas , Humanos , Síndrome de Sézary/tratamiento farmacológico , Estudios Retrospectivos , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Masculino , Femenino , Anciano , Neoplasias Cutáneas/tratamiento farmacológico , Neoplasias Cutáneas/patología , Persona de Mediana Edad , Privación de Tratamiento , Anciano de 80 o más Años , AdultoRESUMEN
Transporter associated with antigen processing (TAP) is essential for the stabilization and surface expression of major histocompatibility complex class I molecules of all nucleated cells. TAP deficiency syndrome, also known as bare lymphocyte syndrome type I, is a rare primary immunodeficiency disorder. We report a case of TAP1 deficiency revealed by skin lesions long before the occurrence of respiratory infectious manifestations.
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Transportador de Casetes de Unión a ATP, Subfamilia B, Miembro 2/genética , Granuloma/patología , Inmunodeficiencia Combinada Grave/diagnóstico , Enfermedades de la Piel/etiología , Preescolar , Femenino , Antígenos de Histocompatibilidad Clase I , Humanos , Mutación , Piel/patologíaAsunto(s)
Predisposición Genética a la Enfermedad , Receptor 2 Celular del Virus de la Hepatitis A/genética , Linfohistiocitosis Hemofagocítica/diagnóstico , Linfohistiocitosis Hemofagocítica/genética , Linfoma de Células T/diagnóstico , Linfoma de Células T/genética , Mutación , Paniculitis/diagnóstico , Paniculitis/genética , Biomarcadores , Femenino , Estudios de Asociación Genética , Humanos , MasculinoRESUMEN
BACKGROUND: The diagnosis of acrodermatitis chronica atrophicans (ACA), the late cutaneous manifestation of Lyme borreliosis, can be challenging. Histologic changes in ACA have been described in a few studies from endemic countries, relying on cases documented by serology only. OBJECTIVES: We sought to reassess the clinicopathological spectrum of ACA in a series of thoroughly documented cases. METHODS: Patients prospectively included in a national prospective study were selected on the basis of positive culture and/or polymerase chain reaction of a skin biopsy sample. The diagnosis of ACA was confirmed by reviewing the clinical and serologic data. Histopathological samples were carefully reviewed. RESULTS: Twenty patients were included. Unusual clinical features (ie, numerous small violaceous patches and equidistant small spinous papules with background faint erythema) were observed in 2 patients. Histopathological examination revealed a classic plasma cell-rich perivascular and interstitial pattern with telangiectases in 16 of 25 samples, whereas strikingly prominent granuloma annulare-like or lichenoid features were observed in 4 and 2 of 25 cases, respectively, and discrete nonspecific minor changes in 3 of 25 cases. LIMITATIONS: The small number of patients was a limitation. CONCLUSIONS: Genuine culture- and/or polymerase chain reaction-proven ACA can rarely present as numerous violaceous patches or cluster of spinous papules clinically, and as a granuloma annulare-like or lichenoid dermatosis histologically.
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Acrodermatitis/diagnóstico , Borrelia burgdorferi/aislamiento & purificación , Eritema Crónico Migrans/diagnóstico , Enfermedad de Lyme/diagnóstico , Reacción en Cadena de la Polimerasa/métodos , Acrodermatitis/microbiología , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Biopsia con Aguja , Estudios de Cohortes , ADN Bacteriano/análisis , Eritema Crónico Migrans/epidemiología , Femenino , Francia/epidemiología , Humanos , Inmunohistoquímica , Incidencia , Enfermedad de Lyme/epidemiología , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Medición de Riesgo , Índice de Severidad de la Enfermedad , Distribución por SexoRESUMEN
The treatment of advanced stage primary cutaneous T-cell lymphomas remains challenging. In particular, large-cell transformation of mycosis fungoides is associated with a median overall survival of two years for all stages taken together. Little is known regarding allogeneic hematopoietic stem cell transplantation in this context. We performed a multicenter retrospective analysis of 37 cases of advanced stage primary cutaneous T-cell lymphomas treated with allogeneic stem cell transplantation, including 20 (54%) transformed mycosis fungoides. Twenty-four patients (65%) had stage IV disease (for mycosis fungoides and Sézary syndrome) or disseminated nodal or visceral involvement (for non-epidermotropic primary cutaneous T-cell lymphomas). After a median follow up of 29 months, 19 patients experienced a relapse, leading to a 2-year cumulative incidence of relapse of 56% (95%CI: 0.38-0.74). Estimated 2-year overall survival was 57% (95%CI: 0.41-0.77) and progression-free survival 31% (95%CI: 0.19-0.53). Six of 19 patients with a post-transplant relapse achieved a subsequent complete remission after salvage therapy, with a median duration of 41 months. A weak residual tumor burden before transplantation was associated with increased progression-free survival (HR=0.3, 95%CI: 0.1-0.8; P=0.01). The use of antithymocyte globulin significantly reduced progression-free survival (HR=2.9, 95%CI: 1.3-6.2; P=0.01) but also transplant-related mortality (HR=10(-7), 95%CI: 4.10(-8)-2.10(-7); P<0.001) in univariate analysis. In multivariate analysis, the use of antithymocyte globulin was the only factor significantly associated with decreased progression-free survival (P=0.04). Allogeneic stem cell transplantation should be considered in advanced stage primary cutaneous T-cell lymphomas, including transformed mycosis fungoides.
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Trasplante de Células Madre Hematopoyéticas , Linfoma Cutáneo de Células T/patología , Linfoma Cutáneo de Células T/terapia , Adolescente , Adulto , Trasplante de Médula Ósea/efectos adversos , Niño , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Francia , Supervivencia de Injerto , Enfermedad Injerto contra Huésped/etiología , Enfermedad Injerto contra Huésped/prevención & control , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Linfoma Cutáneo de Células T/mortalidad , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Recurrencia , Donantes de Tejidos , Acondicionamiento Pretrasplante , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Retrospective data have suggested the effectiveness of intravenous immunoglobulins (IVIG) for solar urticaria (SU). OBJECTIVE: We sought to prospectively assess the efficacy of IVIG for SU. METHODS: We conducted a multicentric phase II study to test the efficacy of a single course of IVIG (2 g/kg) in patients with severe and refractory SU. The primary outcome was remission of SU on phototesting at 12 weeks after IVIG treatment. Secondary objectives included clinical remission, improved quality of life, and 50% improvement in disease intensity as measured on a visual analog scale. RESULTS: Of the 9 patients who received IVIG injection, 2 showed remission of SU on phototesting, corresponding to a response rate of 22.2% (95% confidence interval 2.8%-60.0%). In all, 6 patients (67%) showed at least 1 response criterion after 4 weeks and 5 (56%) after 12 weeks. Response was maintained after 24 weeks for 2 patients and after 48 weeks for 1 patient. About half of the patients (56%) had moderate to severe headache. LIMITATIONS: Lack of control arm and small number of patients are limitations. CONCLUSION: A single course of IVIG appears insufficient to obtain prolonged significant control of SU; future evaluation of different schedules of IVIG administration is warranted.
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Inmunoglobulinas Intravenosas/uso terapéutico , Factores Inmunológicos/uso terapéutico , Trastornos por Fotosensibilidad/tratamiento farmacológico , Urticaria/tratamiento farmacológico , Adulto , Femenino , Humanos , Inmunoglobulinas Intravenosas/efectos adversos , Factores Inmunológicos/efectos adversos , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/etiología , Estudios Prospectivos , Calidad de Vida , Índice de Severidad de la Enfermedad , Luz Solar/efectos adversos , Urticaria/etiología , Adulto JovenRESUMEN
Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p = 0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p = 0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p = 0.013). Interpretation: Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. Funding: French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.
RESUMEN
Photo-recall phenomenon is a phototoxic eruption occurring on areas of previous ultraviolet-induced solar erythema following a systemic administration of a drug. It has been mostly described with methotrexate but remains rare with other antineoplastic drugs. We describe a case of docetaxel-induced photo-recall skin rash in a woman treated for a non-small-cell lung cancer. Although the patient has refused to receive a second infusion, chemotherapy can be carried on with photoprotection and the use of topical and/or systemic corticosteroids. In contrast, radiation recall is a well-known reaction by oncologists, most of them may not be aware of a similar phenomenon called photo-recall phenomenon. Recognizing this entity may avoid misdiagnosing a drug allergy and should avoid inappropriate decisions of drug discontinuation.
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Antineoplásicos/efectos adversos , Dermatitis Fototóxica/etiología , Dermatitis Fototóxica/patología , Taxoides/efectos adversos , Administración Tópica , Corticoesteroides/administración & dosificación , Antineoplásicos/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/patología , Dermatitis Fototóxica/tratamiento farmacológico , Docetaxel , Femenino , Humanos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Persona de Mediana Edad , Taxoides/administración & dosificaciónRESUMEN
BACKGROUND: Advanced mycosis fungoides (MF) and Sézary syndrome (SS) are rare, aggressive cutaneous T-cell lymphomas that may be difficult to treat. Mogamulizumab is a recent monoclonal antibody targeting the CCR4 receptor expressed on the surface of Sézary cells. It can be prescribed in MF/SS stages III to IV in the second line after systemic therapy or in stages IB-II after two unsuccessful systemic therapies. We lack data on long-term efficiency and potential side effects in real-life conditions. Our study aims to determine efficacy considering the median PFS of advanced CTCL with mogamulizumab. Secondary objectives were to consider tolerance and estimate delay until side effects appeared. METHODS: Data on patients with advanced cutaneous T-cell lymphomas were collected since French Authorization, in six French university hospitals. Patients were followed until they stopped mogamulizumab because of relapse or toxicity. For those still treated by mogamulizumab, the end point was 1 September 2021. We excluded 3 patients as they had already been included in the MAVORIC study and data was not available. RESULTS: The median time of follow-up was 11.6 months. Of the 21 patients included, we reported four full-response patients, eight in partial response, one in stability, three in progression, and five were deceased. One patient had visceral progression, and seven had new lymphadenopathy. Progression-free survival was estimated at 22 months. Twenty patients presented adverse events, of which 10 were severe, i.e., grade III-IV. The median time between the introduction of mogamulizumab and the first adverse event was 21 days. CONCLUSIONS: Our study suggests that mogamulizumab can give patients with advanced refractory CTCL a consequent PFS, estimated at 22 months. The long-term safety of mogamulizumab was determined to be acceptable since we reported few grade III-IV AEs, comparable with other studies. No other study using real-life data has been performed to investigate the AEs of mogamulizumab.
RESUMEN
BACKGROUND: Solar urticaria (SU) is a rare idiopathic photodermatosis induced immediately after sun exposure. This disorder may considerably restrict normal daily life and management is extremely difficult when treatment with oral H1 antihistamines and sun avoidance are ineffective. OBJECTIVE: We sought to report the effectiveness of intravenous immunoglobulins (IVIG) in severe SU. METHODS: We performed a retrospective multicentric study via the mailing of a questionnaire to the French photodermatology units to analyze all cases of patients with SU who were treated with IVIG. RESULTS: Seven patients (5 women) with a mean age of 40 years (range 32-55 years) and a mean disease duration of 5 years (range 2-10 years) received IVIG. The administration schedule differed from one patient to another: 1.4 to 2.5 g/kg were infused over 2 to 5 days. Five of 7 patients obtained a complete remission. The number of courses necessary to obtain clinical remission varied from 1 to 3 courses. Complete remission was maintained during 4 to more than 12 months but antihistamines were still required. In one case, psoralen plus ultraviolet A photochemotherapy was administered. LIMITATIONS: Retrospective study design, limited number of patients, and variations in the IVIG administration schedule could limit the interpretation of the results. CONCLUSION: Our case series suggests a beneficial effect of IVIG in severe SU but additional prospective trials including a larger number of patients are needed to demonstrate the effectiveness of IVIG and to specify the optimal modalities of their administration in this disease.
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Inmunoglobulinas Intravenosas/administración & dosificación , Trastornos por Fotosensibilidad/tratamiento farmacológico , Luz Solar/efectos adversos , Urticaria/tratamiento farmacológico , Urticaria/etiología , Adulto , Estudios de Cohortes , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Estudios de Seguimiento , Francia , Humanos , Masculino , Persona de Mediana Edad , Trastornos por Fotosensibilidad/etiología , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Dermatofibrosarcoma protuberans (DFSP) is a soft-tissue sarcoma characterized by a high risk of local infiltration. The identification of the COL1A1-PDGFB t(17;22) translocation activating the PDGF pathway led to the use of imatinib in unresectable DFSP, with a response rate of 36-80%. Pazopanib is a multitarget tyrosine kinase inhibitor approved for soft-tissue sarcomas. We conducted a phase II study of patients with unresectable DFSP to evaluate the efficacy and safety of pazopanib. Patients received 800 mg of pazopanib daily. The primary endpoint was the objective response rate defined as the reduction of the largest diameter of the tumor by ≥30% at 6 months or at surgery. A total of 23 patients, including one pretreated with imatinib, were enrolled. With a median follow-up of 6.2 months (interquartile range = 5.6-7.8 months), five patients (22%, 95% confidence interval = 7-22%) had a partial response to pazopanib. The best objective response rate was 30% (95% confidence interval = 13-53%) using Response Evaluation Criteria in Solid Tumors. One patient with metastatic DFSP previously treated with imatinib died after 2.4 months. Nine patients (39%) discontinued the treatment owing to adverse events. Pharmacodynamics analyses of tumor samples were conducted: the enrichment of EGF and the EGFR-associated gene panel was associated with resistance, suggesting that EGFR-targeted therapies could be a therapeutic option to explore in DFSP. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01059656.
Asunto(s)
Dermatofibrosarcoma/tratamiento farmacológico , Indazoles/administración & dosificación , Inhibidores de Proteínas Quinasas/administración & dosificación , Pirimidinas/administración & dosificación , Neoplasias Cutáneas/tratamiento farmacológico , Sulfonamidas/administración & dosificación , Adulto , Anciano , Biomarcadores de Tumor/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Dermatofibrosarcoma/genética , Dermatofibrosarcoma/patología , Resistencia a Antineoplásicos/genética , Factor de Crecimiento Epidérmico/genética , Receptores ErbB/antagonistas & inhibidores , Receptores ErbB/genética , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Humanos , Indazoles/efectos adversos , Masculino , Persona de Mediana Edad , Inhibidores de Proteínas Quinasas/efectos adversos , Pirimidinas/efectos adversos , Criterios de Evaluación de Respuesta en Tumores Sólidos , Piel/efectos de los fármacos , Piel/patología , Neoplasias Cutáneas/genética , Neoplasias Cutáneas/patología , Sulfonamidas/efectos adversos , Carga Tumoral/efectos de los fármacosAsunto(s)
Ciclosporina/uso terapéutico , Dermatitis Fotoalérgica/tratamiento farmacológico , Inmunosupresores/uso terapéutico , Luz Solar/efectos adversos , Urticaria/tratamiento farmacológico , Adulto , Dermatitis Fotoalérgica/etiología , Femenino , Francia , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del Tratamiento , Urticaria/etiología , Adulto JovenRESUMEN
BACKGROUND: Atopic dermatitis is a highly prevalent, chronic, relapsing disease in both adults and children. On the severity spectrum, lower-end patients benefit from small amounts of topical anti-inflammatory treatments (TAT), whereas higher-end patients need systemic immunosuppressants; in-between patients are treated with TAT and phototherapy. The major therapeutic challenge in this population is the long-term control of disease activity, and the current TAT-based pro-active strategy does not meet all their needs. Immunosuppressants are used as long-term control add-on treatments, but they are restricted to the most severely affected patients because of safety concerns. In addition, neither immunosuppressants nor other strategies have been properly evaluated in the long term despite long-term control having been acknowledged as one of the most important core outcome domains to be targeted in atopic dermatitis trials. Safe add-on therapies, rigorously evaluated for long-term control of the disease, are therefore needed. Phototherapy and vitamin D supplementation are both good candidates. METHODS: This is a multicenter, national, randomized, superiority, crossover trial testing add-on phototherapy (one winter under spaced sessions of phototherapy and one winter under observation) among subjects receiving standard care (i.e., TAT). On the same population, we will test the long-term control provided by oral supplementation of vitamin D versus placebo in a randomized, superiority, double-blind, parallel-group trial. The primary outcomes are (1) repeat measures of the PO-SCORAD severity score over 1 year and (2) cumulate consumption of TAT (number of tubes) during the winter. They will be tested following a hierarchical testing procedure. The secondary outcomes will be measures repeated over 2 years of investigator-based severity scores, patient-reported severity and quality of life scores, serum vitamin D levels, weeks during which the disease is well-controlled, inter-visit cumulate consumption of TAT, and synthetic patient-reported satisfaction at the end of each winter. DISCUSSION: This study includes two separate 2-year pragmatic trials designed to evaluate the efficacy of vitamin D supplementation and pro-active phototherapy for primary care atopic dermatitis patients receiving TAT on long-term control of disease activity. The experimental design enables the study of both interventions and exploration of the interaction between vitamin D and phototherapy. A pragmatic trial is particularly suited to the assessment of long-term control. This study explores the possibility of new and safe therapeutic strategies for the control of long-term atopic dermatitis, and is an example of efficacy research that is unlikely to be sponsored by industrialists. A potentially effective low-cost therapeutic strategy for long-term control is essential for patients and public health. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02537509 , first received: 1 September 2015.