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1.
J Eur Acad Dermatol Venereol ; 34(7): 1489-1495, 2020 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31955469

RESUMEN

BACKGROUND: Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare, aggressive type of haematologic precursor malignancy primarily often manifesting in the skin. We sought to provide a thorough clinical characterization and report our experience on therapeutic approaches to BPDCN. METHODS: In the present multicentric retrospective study, we collected all BPDCN cases occurring between 05/1999 and 03/2018 in 10 secondary care centres of the German-Swiss-Austrian cutaneous lymphoma working group. RESULTS: A total of 37 BPDCN cases were identified and included. Almost 90% of the patients had systemic manifestations (bone marrow, lymph nodes, peripheral blood) in addition to skin involvement. The latter presented with various types of cutaneous lesions: nodular (in more than 2/3) and bruise-like (in 1/3) skin lesions, but also maculopapular exanthema (in circa 1/6). Therapeutically, 22 patients received diverse combinations of chemotherapeutic regimens and/or radiotherapy. Despite initial responses, all of them ultimately relapsed and died from progressive disease. Eleven patients underwent haematopoietic stem cell transplantation (HSCT; autologous HSCT n = 3, allo-HSCT n = 8). The mortality rate among HSCT patients was only 33.33% with a median survival time of 60.5 months. CONCLUSION: Our study demonstrates the clinical diversity of cutaneous BPDCN manifestations and the positive development observed after the introduction of HSCT.


Asunto(s)
Neoplasias Hematológicas , Neoplasias Cutáneas , Austria , Células Dendríticas , Neoplasias Hematológicas/terapia , Humanos , Estudios Retrospectivos , Neoplasias Cutáneas/terapia
2.
J Eur Acad Dermatol Venereol ; 25(8): 922-7, 2011 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-21054571

RESUMEN

BACKGROUND: The Langerhans cell (LC) hypothesis suggests that cutaneous T-cell lymphomas (CTCL) are diseases of chronic T-cell stimulation by LC-mediated antigen presentation. OBJECTIVE: To investigate a broad panel of CTCL and cutaneous B-cell lymphomas (CBCL) for the spatial association of langerin(+) dendritic cells (DC) with T and B cells in the skin, respectively. METHODS: Fifty-five specimens of CTCL and 10 of CBCL were double-stained with monoclonal antibodies against langerin and CD3 or CD20, respectively, and evaluated by confocal laser scan microscopy. RESULTS: Dermal infiltrates in mycosis fungoides (n = 38), primary cutaneous CD4+ small/medium-sized pleomorphic T-cell lymphoma (n = 3) and primary cutaneous peripheral T-cell lymphoma, unspecified (n = 3) were characterized by a high frequency of dermal langerin(+) DCs. These cells were exclusively present in the malignant infiltrates. No direct co-localization of CD3 and langerin could be resolved. Dermal langerin(+) cells were detected only in one of six primary cutaneous anaplastic large cell lymphomas (C-ALCL), characterized by epidermotropism. In other C-ALCL cases (five of six), in lymphomatoid papulosis (n = 3), subcutaneous panniculitis-like T-cell lymphoma (n = 2), and all variants of CBCL no dermal langerin(+) DCs could be found. CONCLUSIONS: Langerin(+) DCs are abundant in the dermal infiltrates of T-cell lymphomas with specific involvement of the epidermis. This might indicate that immature LC and neoplastic T cells interact and gives rise to further studies to characterize the phenotype of the langerin(+) cell population described here and its role in the pathology of CTCL.


Asunto(s)
Antígenos CD/metabolismo , Células Dendríticas/metabolismo , Lectinas Tipo C/metabolismo , Linfoma de Células B/patología , Linfoma Cutáneo de Células T/patología , Lectinas de Unión a Manosa/metabolismo , Neoplasias Cutáneas/patología , Adulto , Anciano , Anciano de 80 o más Años , Antígenos CD20/metabolismo , Complejo CD3/metabolismo , Células Dendríticas/patología , Femenino , Humanos , Inmunohistoquímica , Linfoma de Células B/metabolismo , Linfoma Cutáneo de Células T/metabolismo , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/metabolismo , Adulto Joven
3.
J Eur Acad Dermatol Venereol ; 24(1): 13-7, 2010 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-19515078

RESUMEN

BACKGROUND: Monitoring and repeated staging is of substantial importance in many patients with primary cutaneous T-cell lymphomas (CTCL). For primary cutaneous B-cell lymphomas (CBCL), extensive initial staging is the mainstay for correct diagnosis. AIM: To evaluate the value of somatostatin receptor scintigraphy using the radiolabeled somatostatin analog (111)In-pentetreotide in comparison to conventional imaging methods for the staging of patients with primary CTCL and primary CBCL. METHODS: Twenty-two patients (15 patients with histologically verified CTCL and 7 patients with histologically verified CBCL) were included. Stage of disease was established by physical examination, laboratory screening, skin inspection, palpation of superficial lymph nodes, sonography and computed tomography (CT) in patients with advanced clinical stage. Focally elevated tracer uptake of (111)In-pentetreotide was compared to common imaging modalities, physical aspect and digital photographs of the respective skin lesions. RESULTS: Of the 15 patients with CTCL, only 4 (27%) showed positive scintigraphic results, but not in all sites of lymphomatous involvement. None of the five patients with mycosis fungoides in stage I, nor any of the four patients with Sézary syndrome, had a positive (111)In- pentetreotide scan. Of the seven patients with CBCL three positive scintigraphic results (43%) could be obtained: in two patients with a follicular center lymphoma and one patient with a diffuse large B-cell lymphoma - leg type, but again not in all apparent sites of lymphoma. CONCLUSIONS: Based on our results, we do not recommend the use of somatostatin receptor scintigraphy for routine staging of patients with CTCL and CBCL. As our series includes only 22 patients, and the number of patients with rarer variants of CTCL was rather small, it might be too premature to abandon SST-R in the staging of patients with cutaneous lymphomas.


Asunto(s)
Linfoma de Células B/fisiopatología , Linfoma de Células T/fisiopatología , Cintigrafía/métodos , Receptores de Somatostatina/metabolismo , Neoplasias Cutáneas/fisiopatología , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B/diagnóstico , Linfoma de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Neoplasias Cutáneas/diagnóstico
4.
Ann Oncol ; 20(2): 326-30, 2009 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18836086

RESUMEN

BACKGROUND: We have carried out a retrospective analysis to evaluate the therapeutic value of the anti-CD20 antibody rituximab in 16 consecutive patients with primary cutaneous CD20+ B-cell lymphomas. PATIENTS AND METHODS: Sixteen patients (4 females, 12 males) with a median age of 54 years received systemic therapy with rituximab 375 mg/m(2) once weekly for four or six consecutive weeks. Eleven patients had primary cutaneous follicle center cell lymphoma and five patients had a primary cutaneous marginal zone B-cell lymphoma. RESULTS: Of the 16 patients with PCBCL, 14 patients (87.5%) achieved complete remission (CR). In two patients, partial remission was obtained and additional focal radiotherapy was applied, which resulted in final CR. Five to 14 (35%) patients with CR relapsed, in an interval between 6 and 37 months. There were no severe side-effects. CONCLUSIONS: On the basis of our results, single-agent treatment with i.v. rituximab appears to be feasible and safe and results in a high rate of durable remissions. Judging from our data, it appears to be an attractive treatment option and should be directly compared with local radiotherapy.


Asunto(s)
Anticuerpos Monoclonales/uso terapéutico , Linfoma de Células B/tratamiento farmacológico , Neoplasias Cutáneas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales de Origen Murino , Linfocitos B/inmunología , Linfocitos B/patología , Ensayos Clínicos como Asunto , Análisis Citogenético , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Estudios de Seguimiento , Humanos , Inmunohistoquímica , Factores Inmunológicos/administración & dosificación , Factores Inmunológicos/uso terapéutico , Infusiones Intravenosas , Estimación de Kaplan-Meier , Linfoma de Células B/inmunología , Linfoma de Células B/patología , Linfoma de Células B/terapia , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Linfoma de Células B de la Zona Marginal/inmunología , Masculino , Persona de Mediana Edad , Inducción de Remisión , Rituximab , Neoplasias Cutáneas/inmunología , Neoplasias Cutáneas/patología , Neoplasias Cutáneas/terapia , Factores de Tiempo , Resultado del Tratamiento
5.
Clin Exp Dermatol ; 34(8): e962-4, 2009 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-20055873

RESUMEN

Overexpression of hypoxia inducible factor (HIF)-1alpha has been found in several human cancers and is thought to correlate with aggressive disease and poor response. A retrospective analysis was carried out on 89 patients with primary cutaneous melanoma. HIF-1alpha expression was assessed by immunohistochemistry in formalin-fixed, paraffin wax-embedded tumour sections. Overall survival (OS) and disease-free survival (DFS) were determined using univariate and multivariate analyses. Of the 89 patients, 78 (87.6%) expressed HIF-1alpha, and the remaining 11 patients (12.4%) did not. HIF-1alpha expression correlated with age (P = 0.002), but not with the main predictive factors in melanoma. Survival analysis disclosed no difference between the groups for OS and DFS. In multivariate analysis, only Breslow Index and ulceration were significantly associated with poor OS. Our results indicate that HIF-1alpha overexpression is present in most primary melanomas, but is not associated with clinicopathological variables, patient prognosis or survival.


Asunto(s)
Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Hipoxia/patología , Melanoma/patología , Anciano , Biomarcadores de Tumor/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Hipoxia/genética , Masculino , Pronóstico , Estudios Retrospectivos
6.
J Clin Oncol ; 17(3): 902-6, 1999 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-10071282

RESUMEN

PURPOSE: To evaluate the efficacy and tolerance of combined irinotecan and oxaliplatin in patients with advanced colorectal cancer pretreated with leucovorin-modulated fluoropyrimidines. PATIENTS AND METHODS: Thirty-six patients with metastatic colorectal cancer, who progressed while receiving or within 6 months after discontinuing palliative chemotherapy with fluoropyrimidines/leucovorin, were enrolled onto this study. Treatment consisted of oxaliplatin 85 mg/m2 on days 1 + 15 and irinotecan 80 mg/m2 on days 1 + 8 + 15 every 4 weeks. Depending on the absolute neutrophil counts (ANC) on the day of scheduled chemotherapeutic drug administration, a 5-day course of granulocyte colony-stimulating factor (G-CSF) 5 microg/kg/d was given. RESULTS: The overall response rate was 42% for all 36 assessable patients (95% confidence interval, 26% to 59%), including two complete remissions (6%). Thirteen additional patients (36%) had stable disease, and only eight (22%) progressed. The median time to treatment failure was 7.5 months (range, 1 to 13.5+ months). After a median follow-up time of 14 months, 19 patients (53%) are still alive. Hematologic toxicity was commonly observed, although according to the ANC-adapted use of G-CSF (in 31 patients during 81 of 174 courses), it was generally mild: grade 3 and 4 granulocytopenia occurred in only five and two cases, respectively. The most frequent nonhematologic adverse reactions were nausea/emesis and diarrhea, which were rated severe in 17% and 19%, respectively. CONCLUSION: Our data suggest that the combination of irinotecan and oxaliplatin with or without G-CSF has substantial antitumor activity in patients with progressive fluoropyrimidine/leucovorin-pretreated colorectal cancer. Overall toxicity was modest, with gastrointestinal symptoms constituting the dose-limiting side effects. Further evaluation of this regimen seems warranted.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Colorrectales/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Camptotecina/administración & dosificación , Camptotecina/análogos & derivados , Quimioterapia Adyuvante , Neoplasias Colorrectales/patología , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Enfermedades Hematológicas/inducido químicamente , Humanos , Irinotecán , Masculino , Persona de Mediana Edad , Náusea/inducido químicamente , Compuestos Organoplatinos/administración & dosificación , Oxaliplatino
7.
Eur J Cancer ; 40(3): 358-64, 2004 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-14746853

RESUMEN

Few data on the influence of lymphatic microvessel density (LMVD) on survival in patients with melanoma are available. The aim of this study was to assess LMVD and blood microvessel density (MVD) in tissue samples from 120 patients with melanoma. LMVD was stained with an antibody staining for podoplanin, and blood MVD was assessed by CD31 (PECAM-1)-immunostaining. Survival was determined using univariate and multivariate analysis. A significant association between a high CD31 MVD (but not LMVD) and the presence of lymph node metastases (P=0.007) was observed. Patients with a high LMVD had a significant shorter overall (OS) (P=0.0436) and disease-free survival (DFS) (P=0.0249) in univariate analysis. The survival analysis showed CD31 MVD was a strong prognostic factor for OS and DFS in both uni-and multivariate analyses. Our results demonstrate LMVD as a prognostic factor in malignant melanoma, although its prognostic relevance is much smaller compared with blood MVD.


Asunto(s)
Melanoma/patología , Neoplasias Cutáneas/patología , Adulto , Anciano , Humanos , Inmunohistoquímica/métodos , Metástasis Linfática/patología , Sistema Linfático/irrigación sanguínea , Melanoma/irrigación sanguínea , Microcirculación , Persona de Mediana Edad , Análisis Multivariante , Neoplasias Cutáneas/irrigación sanguínea , Análisis de Supervivencia
8.
Eur J Cancer ; 34(7): 1128-30, 1998 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-9849466

RESUMEN

Recent data have suggested enhanced therapeutic activity with prolonged administration of both etoposide as well as fluoropyrimidines in the treatment of gastrointestinal malignancies. Based on this rationale, we investigated the clinical effectiveness and tolerance of an oral modification of the widely applied etoposide, leucovorin and 5-fluorouracil (ELF) regimen in patients with advanced gastric cancer. 32 patients with advanced gastric cancer were treated with oral etoposide (100 mg), leucovorin (3 x 100 mg), and tegafur (3 x 200 mg) over 14-21 days for a maximum of six cycles. Objective response was seen in only 5 patients (16%), stable disease was documented in 7 (22%), while the remaining patients progressed during therapy. The median time to progression was 2.8 months (range 0.7-12 months) and median overall survival was 6 months (range 1-18+ months). Due to grade 3 nausea/emesis, 8 patients discontinued treatment prematurely, while 12 patients experienced anorexia and progressive weight loss. Haematological toxicity was modest, with 4 patients developing asymptomatic grade 3-4 granulocytopenia. We conclude that this oral combination regimen cannot be recommended for the treatment of advanced gastric cancer.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Gástricas/tratamiento farmacológico , Administración Oral , Adulto , Anciano , Etopósido/administración & dosificación , Femenino , Fluorouracilo/administración & dosificación , Humanos , Leucovorina/administración & dosificación , Levoleucovorina , Masculino , Persona de Mediana Edad , Tegafur/administración & dosificación , Resultado del Tratamiento
9.
Anticancer Res ; 21(4B): 3049-52, 2001.
Artículo en Inglés | MEDLINE | ID: mdl-11712809

RESUMEN

BACKGROUND: Serum levels of beta-2 microglobulin (B2M) have been reported as a predictor of clinical outcome, prognosis and tumor burden in patients with various types of lymphomas. In case of lymphoma of the mucosa-associated lymphoid tissue (MALT)-type, no clear data exist to define the role of B2M in terms of staging or prognosis. In a retrospective analysis we investigated the serum B2M-levels in patients suffering from histologically verified MALT-type lymphoma in correlation to stage and response to treatment. PATIENTS AND METHODS: All patients admitted to our institution since 1996 with a diagnosis of MALT-type lymphoma were retrospectively evaluated for staging procedures and measurements of serum B2M levels. Patients with a staging work-up including otorhinolaryngologic evaluation, gastroscopy with multiple biopsies, endosonography of the upper GI-tract, enteroclysis, colonoscopy, CT of thorax and abdomen and bone marrow biopsy were analysed, while staging was performed according to the Ann Arbor system as modified by Musshoff. In addition, only patients with histologic samples amenable to re-assessment by a reference pathologist were included. RESULTS: A total of 68 patients with a diagnosis of MALT-type lymphoma were identified from our records. However, only in 32 patients exact staging according to our inclusion criteria had been performed and serum B2M-levels prior to the initiation of therapy were available in all these patients. Twenty-five patients; suffered from gastric lymphoma, while the remaining 7 patients had extragastric manifestations. In total, 13 out of 32 patients presented with stage I disease, 17 patients were rated as stage II and 2 patients suffered from stage III disease. Nineteen patients had elevated B2M-levels prior to therapy: 6 patients were rated as stage 1, II had stage II and two had stage III disease. Five patients still had elevated B2M-levels following treatment despite radiologically and histologically verified complete remission. CONCLUSION: In this series, no correlation between serum B2M levels, tumor burden and clinical outcome was apparent in patients with MALT-type lymphomas. While the number of patients with disseminated disease was small we could not demonstrate a difference for B2M-levels between stage I and stage II. While we cannot rule out that B2M might be different in patients with stage I/II disease as compared to more advanced disease, further investigations are necessary to determine the role of this marker in patients with MALT-type lymphoma.


Asunto(s)
Biomarcadores de Tumor/sangre , Linfoma de Células B de la Zona Marginal/sangre , Proteínas de Neoplasias/sangre , Microglobulina beta-2/análisis , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Linfoma de Células B de la Zona Marginal/patología , Linfoma de Células B de la Zona Marginal/terapia , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Resultado del Tratamiento
13.
Ann Hematol ; 81(11): 662-5, 2002 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-12454707

RESUMEN

A 58-year-old woman with a 15-year history of chronic plaque psoriasis was diagnosed with gastric marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT) type. Topical treatment and ultraviolet radiation for therapy of psoriasis had been of limited efficacy. The patient received intravenous treatment with 0.12 mg/kg per day of 2-chlorodeoxyadenosine (2-CDA) over 5 days for management of MALT lymphoma, as it was resistant to eradication of Helicobacter pylori. A total of six cycles were administered from June 1999 until November 1999 (cumulative dose 244.8 mg 2-CDA). After 2 months of 2-CDA administration, psoriatic skin lesions improved significantly, and after 3 months, complete remission of skin lesions was observed. Ongoing complete remission of the MALT lymphoma could be achieved after six cycles of 2-CDA administration. After a follow-up period of 34 months, no recurrence of psoriatic lesions has occurred. The patient is at present free of psoriatic plaques and gastric MALT lymphoma. The course of disease in our patient provides evidence for sustained therapeutic efficacy of 2-CDA in chronic plaque psoriasis in the absence of severe side effects except asymptomatic lymphopenia.


Asunto(s)
Cladribina/administración & dosificación , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Psoriasis/tratamiento farmacológico , Neoplasias Gástricas/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Enfermedad Crónica , Femenino , Humanos , Inmunosupresores/administración & dosificación , Linfoma de Células B de la Zona Marginal/complicaciones , Persona de Mediana Edad , Psoriasis/etiología , Inducción de Remisión/métodos , Neoplasias Gástricas/complicaciones
14.
J Hand Surg Am ; 24(5): 1103-8, 1999 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-10509292

RESUMEN

The topography of the nerve of Henle was reviewed. Fifty-two human cadaveric upper extremities were studied. In 30 (58%) the nerve was well defined; in 22 (42%) its origin from the ulnar nerve was unidentifiable. The palmar cutaneous branch of the ulnar nerve separated from the ulnar nerve 5 to 11 cm distal to the medial epicondyle of the humerus to divide into its terminal branches in the distal forearm. Four patterns were detected: ulnar, radioulnar, vessel-related, and radial. These shared a consistent vascular branch, which sent 2 branches to the ulnar artery just proximal to the distal ulnar tunnel. Using a tyrosine hydroxylase antibody-based immunohistochemistry technique the nerve was shown to carry sympathetic fibers. Motor fibers were ruled out with Karnovsky's stain, which was used in combination with the tyrosine hydroxylase method in 10 specimens.


Asunto(s)
Antebrazo/inervación , Nervio Cubital/anatomía & histología , Adulto , Anciano , Humanos , Inmunohistoquímica , Persona de Mediana Edad , Arteria Cubital/anatomía & histología , Muñeca/inervación
15.
Gut ; 46(1): 133-5, 2000 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-10601069

RESUMEN

BACKGROUND: Lymphoma of the mucosa associated lymphoid tissue (MALT) arising in the stomach has been shown to be related to Helicobacter pylori infection, and total regression of gastric lymphoma after successful eradication of H pylori has consistently been reported. MALT-type lymphoma at other localisations, however, has to our knowledge not been linked to H pylori, and eradication of the bacteria has not been studied for management of such lymphomas. PATIENT/METHOD: A 67 year old man was diagnosed with MALT-type lymphoma simultaneously involving the stomach and the colon descendens. In addition to the presence of MALT-type lymphoma, H pylori associated chronic gastritis was diagnosed, and treatment with clarithromycin, metronidazole, and omeprazole was initiated, resulting in its successful eradication. RESULTS: Follow up performed four months later showed regression of the colonic manifestation, whereas the gastric lymphoma did not respond to antibiotic treatment, as assessed by regular follow up for 14 months, in spite of its restriction to mucosa and submucosa. The patient was therefore treated with oral cyclophosphamide (100 mg a day) resulting in partial remission after seven months of continuous treatment. Because of the presence of residual lymphoma, additional irradiation was performed, which led to complete remission of the gastric lymphoma. The patient remains in complete remission 40 months after diagnosis and 26 months after initiation of treatment. CONCLUSION: In the case of concurrent gastric and intestinal low grade MALT-type lymphoma, H pylori eradication may cause regression of the intestinal lesion.


Asunto(s)
Neoplasias del Colon/microbiología , Infecciones por Helicobacter/complicaciones , Helicobacter pylori , Linfoma de Células B de la Zona Marginal/microbiología , Anciano , Antibacterianos/uso terapéutico , Antiulcerosos/uso terapéutico , Claritromicina/uso terapéutico , Neoplasias del Colon/tratamiento farmacológico , Quimioterapia Combinada , Estudios de Seguimiento , Infecciones por Helicobacter/tratamiento farmacológico , Humanos , Linfoma de Células B de la Zona Marginal/tratamiento farmacológico , Masculino , Metronidazol/uso terapéutico , Omeprazol/uso terapéutico
16.
J Neurooncol ; 49(3): 263-8, 2000 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-11212906

RESUMEN

A pregnant 33-year old woman developed nystagmus and cerebellar ataxia. A tumor in the roof of the fourth ventricle was diagnosed. The tumor was subtotally removed using microneurosurgical techniques. The histopathological diagnosis was choroid plexus papilloma (CPP). Twenty-one months later, the tumor recurred and was reoperated. Histologically the tumor displayed now increased mitotic activity and pleomorphism. Radiation therapy of the neuroaxis was performed. Within 59 months, the CPP recurred 3 more times with neuroradiological evidence of extensive spinal seeding. After several palliative irradiations, including 2 gamma-knife boosts, the patient was referred to chemotherapy. She was treated with CCNU (Lomustin) 100 mg/m2 orally (12 cycles, cumulative dosis 1440 mg/m2). Within 42 months, there was no new local recurrence and spinal seeding showed significant regression. Clinically the patient improved and stabilized, but needs continuous support because of persisting severe gait ataxia. The course of disease in our patient provides evidence for therapeutic efficacy of CCNU in recurrent CPP.


Asunto(s)
Antineoplásicos Alquilantes/uso terapéutico , Neoplasias del Plexo Coroideo/tratamiento farmacológico , Lomustina/uso terapéutico , Papiloma/tratamiento farmacológico , Complicaciones Neoplásicas del Embarazo/tratamiento farmacológico , Adulto , Antineoplásicos Alquilantes/efectos adversos , Neoplasias del Plexo Coroideo/diagnóstico , Neoplasias del Plexo Coroideo/patología , Neoplasias del Plexo Coroideo/cirugía , Terapia Combinada , Femenino , Humanos , Lomustina/efectos adversos , Imagen por Resonancia Magnética , Recurrencia Local de Neoplasia , Siembra Neoplásica , Papiloma/diagnóstico , Papiloma/patología , Papiloma/cirugía , Embarazo , Complicaciones Neoplásicas del Embarazo/diagnóstico , Complicaciones Neoplásicas del Embarazo/patología , Complicaciones Neoplásicas del Embarazo/cirugía , Reoperación
17.
Ann Oncol ; 9(12): 1309-14, 1998 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-9932161

RESUMEN

BACKGROUND: To determine the maximum tolerable dose (MTD) and therapeutic activity of MTHF-modulated FU using two different administration schedules of the antimetabolite (bolus vs. two-hour infusion), the present randomized study using a 'pick-the-winner' design was undertaken in patients with advanced colorectal cancer. PATIENTS AND METHODS: Eighty-two patients with previously untreated advanced measurable colorectal cancer were randomly assigned to treatment with MTHF (100 mg/m2 days 1-5 i.v. bolus) plus FU (400 mg/m2 days 1-5) given either as i.v. bolus injection or as a two-hour infusion every four weeks. In the absence of dose-limiting toxicity (DLT, defined as > or = WHO grade 3 hematotoxicity and/or > or = WHO grade 2 nonhematologic side effects) and evidence of progressive disease, the FU dose was escalated by 50 mg/m2/day during each subsequent cycle until the individual maximum tolerable dose (MTD) was reached. RESULTS: Forty patients were randomized to the FU bolus arm and 42 patients to the FU two-hour infusion arm. The median MTD was 475 mg/m2/day (95% CI: 450-500) in the FU bolus arm with stomatitis +/- diarrhea being the most common DLT. Gastrointestinal side effects were also dose-limiting in the two-hour infusion arm; however, the median MTD was 600 mg/m2/day (95% CI: 568-632). Myelosuppression was more pronounced in the FU bolus arm than in the two-hour infusion arm. The overall response rates were 27.5% (95% CI: 15-44%; 1 CR and 10 PR) for patients treated in the bolus arm and 14.5% (95% CI: 5-28%; 1 CR and 5 PR) for those treated in the two-hour infusion arm. Analogous to recorded response, median time to progression (8.5 vs. 6.25) and overall survival time (14.0 vs. 11.0) tended to be superior in the FU bolus arm. CONCLUSIONS: The observed differences in tolerable drug dose and toxicity between the two treatment arms might be explained by the administration schedule-dependent clinical pharmacokinetics of FU and/or the difference in extent of biochemical modulation of the antimetabolite through MTHF. The fact that the two regimens were not equitoxic probably also helps to explain the favourable response activity noted in the MTHF/FU bolus arm. Whether MTHF is as effective as leucovorin for biochemical modulation of FU remains to be determined in a randomized trial, for which we would recommend its combined use with bolus FU ('winner arm') using a starting dose of 400 mg/m2/day x5.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Antimetabolitos Antineoplásicos/efectos adversos , Enfermedades de la Médula Ósea/prevención & control , Neoplasias Colorrectales/tratamiento farmacológico , Fluorouracilo/efectos adversos , Tetrahidrofolatos/uso terapéutico , Adenocarcinoma/mortalidad , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/uso terapéutico , Enfermedades de la Médula Ósea/inducido químicamente , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Supervivencia sin Enfermedad , Esquema de Medicación , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/uso terapéutico , Humanos , Infusiones Intravenosas , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Inducción de Remisión , Análisis de Supervivencia , Resultado del Tratamiento
18.
Am J Gastroenterol ; 94(1): 278-9, 1999 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-9934776

RESUMEN

Treatment options for hepatocellular cancer apart from surgical resection are limited because of the drug-refractory nature of this disease. Little is known about the role of somatostatin-receptors in hepatocellular cancer, and somatostatin analogs have not been investigated for treatment of this malignancy. We present the case of a 68-yr-old male, who was successfully treated with the long-acting somatostatin analog lanreotide.


Asunto(s)
Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Neoplasias Hepáticas/tratamiento farmacológico , Péptidos Cíclicos/uso terapéutico , Somatostatina/análogos & derivados , Anciano , Carcinoma Hepatocelular/patología , Humanos , Neoplasias Hepáticas/patología , Masculino , Somatostatina/uso terapéutico
19.
Oncology ; 55(6): 538-42, 1998.
Artículo en Inglés | MEDLINE | ID: mdl-9778620

RESUMEN

BACKGROUND: The therapeutic potential of chemotherapy in the treatment of recurrent or metastatic non-small cell lung carcinoma (NSCLC) seems modest. Thus, the search for novel agents and combination regimens with a superior therapeutic index has a high priority. The present combination regimen consisting of mitomycin C, vinorelbine, carboplatin and granulocyte-macrophage colony-stimulating factor (GM-CSF) was chosen because of the known activity of these agents in NSCLC and their potential drug synergism without (nonhematologic) cross-toxicity. To prevent/counteract neutropenia that was assumed to represent the dose-limiting toxicity, the hematopoietic growth factor GM-CSF was routinely adminstered. The objective of our trial was to determine the antitumor efficacy and tolerance of this combination regimen in patients with advanced NSCLC. PATIENTS AND METHODS: Forty consecutive patients with nonresectable, measurable NSCLC (stage IIIB, 7; stage IV, 33) were treated with an intravenous combination chemotherapy regimen consisting of mitomycin C 8 mg/m2 on day 1, vinorelbine 40 mg/m2 on days 1 and 21, and carboplatin 250 mg/m2 on days 1 and 21; GM-CSF 5 microg/kg was administered subcutaneously on days 2-8 and 22-28. Treatment cycles were repeated every 6 weeks. All patients are evaluable in terms of toxicity and response assessment. A total of 123 courses was administered. RESULTS: Objective tumor response was notes in 16 patients (40%; 95% confidence interval 24.9-56.7%), including 3 (7.5%) complete and 13 partial responses. There was no change in 12 (31.5%) patients, and 12 had progressive disease. Median duration of response was 6 (range 3-15) months, the median time to progression for all patients was 6.2 (range 1-17.5) months, and the projected median survival time was 8.7 (range 1-23.3) months; the 1-year survival rate was 27.5%. Myelosuppression was the most frequently encountered adverse reaction; WHO grade 3 or 4 granulocytopenia and/or thrombocytopenia occurred in 42.5 and 12.5%, respectively. Other toxicities were generally mild to moderate, and always fully reversible. CONCLUSION: With a 40% major response rate and disease stabilization in one additional third of our patients, this drug combination seems to have significant activity against advanced metastatic NSCLC. Due to its subjective tolerance and ease of administration, further investigation of this regimen in the palliative-intent care setting seems warranted.


Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Neoplasias Pulmonares/tratamiento farmacológico , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Carboplatino/administración & dosificación , Carcinoma de Pulmón de Células no Pequeñas/patología , Esquema de Medicación , Femenino , Factor Estimulante de Colonias de Granulocitos y Macrófagos/administración & dosificación , Humanos , Inyecciones Intravenosas , Inyecciones Subcutáneas , Neoplasias Pulmonares/patología , Masculino , Persona de Mediana Edad , Mitomicina/administración & dosificación , Estadificación de Neoplasias , Vinblastina/administración & dosificación , Vinblastina/análogos & derivados , Vinorelbina
20.
Br J Cancer ; 80(11): 1797-802, 1999 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-10468299

RESUMEN

Although the novel cytidin analogue gemcitabine has shown superior anti-tumour activity than 5-fluorouracil in advanced pancreatic cancer, further improvements of therapeutic results are warranted. This goal might be achieved by combining gemcitabine with other active drugs. This trial evaluated the efficacy and tolerance of such a combination regimen with epirubicin and granulocyte colony-stimulating factor (G-CSF) in patients with metastatic disease. Seventy patients with metastatic pancreatic adenocarcinoma were enrolled in this multicentre trial. Patients received 4-weekly courses of a combination regimen consisting of epirubicin 60 mg m(-2) given as intravenous bolus injection on day 1, gemcitabine 1000 mg m(-2) infused over 30 min on days 1, 8 and 15, and G-CSF administered at 5 microg kg(-1) day(-1) subcutaneously from days 2-6 during each cycle. The efficacy of treatment was assessed by conventional measures, i.e. objective response, progression-free and overall survival, as well as by analysis of clinical benefit response (defined as > or = 50% reduction in pain intensity, > or = 50% reduction in daily analgesic consumption, and/or > or = 20-point improvement in Karnofsky performance status that was sustained for > or = 4 consecutive weeks). Of 66 patients evaluable for objective response, one achieved complete and 13 partial remissions, for an overall response rate of 21% (95% confidence interval (CI), 12-33%); 27 additional patients (41%) had stable and 25 (38%) increasing disease. The median time to progression was 3.8 months. Median survival was 7.8 months, and the probability of surviving beyond 12 months was 21.2%. Out of 60 patients with tumour-related symptoms, who were considered evaluable for clinical benefit response, 26 (43%) experienced significant palliation. The median time to achieve a clinical benefit response was 7 weeks, and its median duration was 22 weeks. Chemotherapy was well-tolerated with leukopenia/granulocytopenia representing the most common and dose-limiting side-effect. Gastrointestinal and other subjective toxicities were infrequent and generally rated minor. We conclude that the combination of gemcitabine, epirubicin and G-CSF seems to be an effective palliative treatment with only moderate toxic effects in patients with metastatic pancreatic adenocarcinoma. Our results in terms of objective and clinical benefit response, as well as survival seem to suggest an advantage over gemcitabine-monotherapy, though this remains to be confirmed in a randomized trial.


Asunto(s)
Adenocarcinoma/tratamiento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Factor Estimulante de Colonias de Granulocitos/uso terapéutico , Neoplasias Pancreáticas/tratamiento farmacológico , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adulto , Anciano , Antimetabolitos Antineoplásicos/administración & dosificación , Antimetabolitos Antineoplásicos/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Intervalos de Confianza , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Desoxicitidina/análogos & derivados , Epirrubicina/administración & dosificación , Epirrubicina/efectos adversos , Femenino , Estudios de Seguimiento , Factor Estimulante de Colonias de Granulocitos/efectos adversos , Humanos , Masculino , Persona de Mediana Edad , Metástasis de la Neoplasia , Neoplasias Pancreáticas/mortalidad , Neoplasias Pancreáticas/patología , Selección de Paciente , Tasa de Supervivencia , Factores de Tiempo , Gemcitabina
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