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1.
Lupus ; 28(13): 1503-1509, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31623520

RESUMO

Prognosis of pregnancies in women with antiphospholipid syndrome has dramatically improved over the past two decades using conventional treatment with low molecular weight heparin and low-dose aspirin. However, despite this regimen, 10-15% of antiphospholipid syndrome patients experience pregnancy losses. Several studies have been performed in order to identify risk factors predictive of complications. Thrombosis has been generally accepted as the key pathogenetic mechanism underlying pregnancy morbidity. However, the thrombogenic state alone is not able to explain all the different mechanisms leading to pregnancy failure. In fact, emerging evidence shows that complement pathway could play an important role in mediating clinical events in antiphospholipid syndrome. However, the exact mechanism through which complement mediates antiphospholipid syndrome complications remains unknown. Low complement levels (C3 and C4) are associated with poor pregnancy outcome in women with antiphospholipid syndrome in different studies. Hypocomplementemia could be indicated as an early predictor of adverse pregnancy outcome, available at the beginning of pregnancy for starting, if necessary, additional treatment to conventional therapy. However, future studies need to better understand the impact of low complement level on antiphospholipid syndrome pregnancy outcome.


Assuntos
Síndrome Antifosfolipídica/fisiopatologia , Complicações na Gravidez/fisiopatologia , Resultado da Gravidez , Anticoagulantes/administração & dosagem , Ativação do Complemento , Complemento C3/metabolismo , Complemento C4/metabolismo , Feminino , Humanos , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/imunologia , Prognóstico , Fatores de Risco , Trombose/tratamento farmacológico , Trombose/etiologia
3.
Lupus ; 27(10): 1616-1623, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29954281

RESUMO

This longitudinal retrospective study aims at describing the safety profile and the reasons for discontinuation of antimalarials in patients with systemic lupus erythematosus (SLE) and discoid lupus erythematosus (DLE), focusing on ocular toxicity. We analyzed the clinical data of 845 SLE and DLE patients; 59% of them were taking antimalarials: 1.4% chloroquine (CQ), 88.5% hydroxychloroquine (HCQ) and 10.1% both. The mean therapy duration was 82.5 ± 77.4 months. At least one side effect was reported by 19.4% of patients, leading to temporary or permanent withdrawal in 9.1% and 10.3% of cases, respectively; 19.3% of patients experienced side effects with HCQ and 8.6% with CQ. In 55.1% of cases, the adverse event was mild or moderate. Ophthalmological alterations were reported by 8.5% but were confirmed by the ophthalmological examination in 5.5% of cases. Retinal alterations were associated with age, disease duration and duration of the antimalarial therapy, but not to drug dose and comorbidities or lupus nephritis. This is the largest monocentric longitudinal study confirming the good safety profile of antimalarials in DLE and SLE patients. The main adverse events during the therapy were mild or moderate, but maculopathy-reported in a low percentage of patients-remains the main cause of treatment withdrawal.


Assuntos
Antimaláricos/uso terapêutico , Cloroquina/uso terapêutico , Lúpus Eritematoso Discoide/tratamento farmacológico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Adulto , Antimaláricos/efeitos adversos , Cloroquina/efeitos adversos , Feminino , Humanos , Hidroxicloroquina/uso terapêutico , Estudos Longitudinais , Lúpus Eritematoso Discoide/diagnóstico , Lúpus Eritematoso Sistêmico/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Cidade de Roma , Fatores de Tempo , Resultado do Tratamento
4.
Lupus ; 27(5): 841-846, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29157179

RESUMO

The present study investigated: (a) the presence of antiphospholipid antibodies and (b) the obstetric outcome in healthy pregnant women showing false-positive TORCH-Toxoplasmosis, Other: syphilis, varicella-zoster, Rubella, Cytomegalovirus (CMV), and Herpes infections-results. Data from 23 singleton healthy pregnancies with false-positive TORCH results were collected. Each woman was systematically screened for TORCH IgG and IgM during the pre-conception assessment and/or at the beginning of pregnancy. In the presence of IgM positivity, when indicated (CMV, toxoplasmosis, rubella, herpes simplex virus), IgG avidity was evaluated and, if possible, polymerase chain reaction was performed on an amniotic fluid sample in order to distinguish between primary infection or false positivity. The antiphospholipid antibodies tests were: lupus anticoagulant, anticardiolipin antibodies IgG, IgM, and anti-ß2glicoprotein I IgG, IgM. The antiphospholipid antibodies tests, if positive, were repeated after 12 weeks to confirm the results. In pregnant women with false-positive TORCH, the overall prevalence of positive antiphospholipid antibodies for one or more tests was 52.2%. To clarify the correlation of false-positive TORCH results with clinical practice, obstetric outcome was analyzed in terms of live births, week of delivery, neonatal birth weight, and neonatal birth weight percentile. A statistically significant lower neonatal birth weight and neonatal birth weight percentile were observed in women with false-positive TORCH associated with antiphospholipid antibodies positivity (Group A) in comparison with those in women with false-positive TORCH without antiphospholipid antibodies positivity (Group B). No statistically significant difference was found for the week of delivery between the two groups. It is hoped that future studies will verify the life-long persistence of antiphospholipid antibodies positivity by follow-up of these women and identify who will develop a classical antiphospholipid syndrome or other autoimmune disorders.


Assuntos
Anticorpos Antifosfolipídeos/sangue , Síndrome Antifosfolipídica/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Complicações Infecciosas na Gravidez/sangue , Adulto , Síndrome Antifosfolipídica/diagnóstico , Biomarcadores/sangue , Peso ao Nascer , Infecções por Citomegalovirus/sangue , Infecções por Citomegalovirus/diagnóstico , Reações Falso-Positivas , Feminino , Infecções por Herpesviridae/sangue , Infecções por Herpesviridae/diagnóstico , Humanos , Recém-Nascido , Nascido Vivo , Valor Preditivo dos Testes , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Fatores de Risco , Rubéola (Sarampo Alemão)/sangue , Rubéola (Sarampo Alemão)/diagnóstico , Sífilis/sangue , Sífilis/diagnóstico , Toxoplasmose/sangue , Toxoplasmose/diagnóstico , Infecção pelo Vírus da Varicela-Zoster/sangue , Infecção pelo Vírus da Varicela-Zoster/diagnóstico
6.
Autoimmun Rev ; 14(9): 760-2, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25936295

RESUMO

The best therapy regimen for refractory obstetrical antiphospholipid syndrome remains to be determined. Additional treatments with steroids, plasma exchanges and immunoglobulins failed to show any beneficial effect. We present a case of a woman who had a better pregnancy outcome after the administration of hydroxychloroquine (HCQ) as additional treatment. Furthermore, we highlighted that HCQ was able to dramatically reduce the antiphospholipid antibodies levels.


Assuntos
Síndrome Antifosfolipídica/tratamento farmacológico , Hidroxicloroquina/uso terapêutico , Adulto , Anticorpos Antifosfolipídeos/imunologia , Síndrome Antifosfolipídica/imunologia , Feminino , Humanos , Fenótipo , Gravidez , Complicações na Gravidez , Resultado da Gravidez
7.
Lupus ; 24(3): 231-4, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25504650

RESUMO

Neonatal antiphospholipid syndrome (neonatal APS) seems to be exceedingly rare, as the antiphospholipid antibodies (aPL) related thrombosis in the neonatal period. The pathogenesis of perinatal aPL related thrombosis may be explained both by the transplacental passage of the maternal antibodies and by the production of de novo antibodies by the neonate. However, few cases of neonatal APS are reported in the literature, especially regarding arterial thrombotic events. In particular, only two cases of neonatal aPL related isolated cerebral sinovenous thrombosis (CSVT) are described in the literature. Despite its frequency, CSVT results in significant mortality and morbidity, probably also due to the difficulty in early diagnosis and then in correct managing in the neonatal period. A diagnosis of neonatal APS should be considered in the evaluation of neonates with CSVT, as well as in any case of neonatal thrombosis, to correctly manage the affected neonates and counsel the mother for future pregnancies.


Assuntos
Síndrome Antifosfolipídica/complicações , Trombose Intracraniana/imunologia , Humanos , Recém-Nascido , Masculino
8.
Ann Oncol ; 23(12): 3110-3116, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22745214

RESUMO

BACKGROUND: Molecular circadian clocks can modify cancer chemotherapy effects, with a possible moderation according to sex differences. We investigated whether sex determine the optimal delivery schedule of chemotherapy for metastatic colorectal cancer. PATIENTS AND METHODS: A meta-analysis was performed using individual data from three international Phase III trials comparing 5-fluorouracil, leucovorin and oxaliplatin administered in chronomodulated (chronoFLO) or conventional (CONV) infusions. The data from 345 females and 497 males were updated at 9 years. The main end point was survival. RESULTS: Overall survival was improved in males on chronoFLO when compared with CONV (P = 0.009), with respective median values of 20.8 (95% CL, 18.7 to 22.9) and 17.5 months (16.1 to 18.8). Conversely, median survival was 16.6 months (13.9 to 19.3) on chronoFLO and 18.4 months (16.6 to 20.2) on CONV in females (P = 0.012). The sex versus schedule interaction was a strong predictive factor of optimal treatment schedule, with a hazard ratio of 1.59 (1.30 to 1.75) for overall survival (P = 0.002) in multivariate analysis. CONCLUSIONS: Males lived significantly longer on chronomodulated chemotherapy rather than on conventional chemotherapy. The current chronoFLO schedule deserves prospective assessment as a safe and more effective first-line treatment option than conventional delivery for male patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Relógios Circadianos , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/mortalidade , Idoso , Cronoterapia , Esquema de Medicação , Feminino , Fluoruracila/uso terapêutico , Humanos , Leucovorina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica/tratamento farmacológico , Recidiva Local de Neoplasia/tratamento farmacológico , Compostos Organoplatínicos/uso terapêutico , Fatores Sexuais , Taxa de Sobrevida , Resultado do Tratamento
9.
Lupus ; 21(7): 773-5, 2012 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-22635229

RESUMO

OBJECTIVE: The presence of TORCH IgM positivity is not a specific indicator of primary infection; the assessment of IgG avidity index has been shown to be useful in identifying or excluding primary infection in pregnant women with no pre-gestational TORCH serology. TORCH is an acronym for Toxoplasmosis, Others (HBV, syphilis, Varicella-Zoster virus, Epstein Barr virus, Coxsackie virus and Parvovirus), Rubella, Cytomegalovirus (CMV) and Herpes Simplex. PATIENTS AND METHODS: Data from 54 pregnancies in women with antiphospholipid syndrome (APS) were assessed in comparison with data from 222 healthy pregnant women as controls. Each woman in both groups was systematically screened for TORCH IgG and IgM during pre-conceptional evaluation and/or at the beginning of pregnancy. The assessment of IgG avidity was also evaluated in order to identify primary infection or false positivity. RESULTS: A significant increase of CMV IgM false positivity in APS in comparison with controls was detected. A worse pregnancy outcome was observed among APS patients having CMV IgM false positivity in comparison with APS patients without false positivity; in particular a statistically significant lower neonatal birth weight and a lower neonatal birth weight percentile were observed. CONCLUSION: Our data suggest that the presence of CMV IgM false positivity could represent a novel prognostic factor for poor pregnancy outcome in APS patients.


Assuntos
Síndrome Antifosfolipídica/imunologia , Infecções por Citomegalovirus/imunologia , Imunoglobulina M/sangue , Complicações na Gravidez/imunologia , Estudos de Casos e Controles , Reações Falso-Positivas , Feminino , Humanos , Gravidez , Resultado da Gravidez
10.
Ann Oncol ; 23(9): 2313-2318, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22396447

RESUMO

BACKGROUND: Scientific data provide the evidence that secondary K-RAS mutations do not occur during anti-epidermal growth factor receptor therapy in colorectal cancer patients. This multicenter phase II prospective study aims to investigate the activity of a retreatment with a cetuximab-based therapy. PATIENTS AND METHODS: We enrolled 39 irinotecan-refractory patients who had a clinical benefit after a line of cetuximab- plus irinotecan-based therapy and then a progression of disease for which underwent a new line chemotherapy and finally, after a clear new progression of disease, were retreated with the same cetuximab- plus irinotecan-based therapy. RESULTS: Median number of therapeutic lines before accrual was 4. Median interval time between last cycle of first cetuximab-based therapy and first cycle of the retreatment was 6 months. Overall response rate was 53.8% with 19 partial responses (48.7%) and 2 complete responses (5.1%). Disease stabilization was obtained in 35.9% of patients and progression in four patients (10.2%). Median progression-free survival was 6.6 months. The correlation between skin toxicity during first cetuximab therapy and during cetuximab rechallenge was significant (P = 0.01). CONCLUSION: Rechallenge with the same cetuximab-based therapy may achieve a new important clinical benefit further delaying the progression of disease and improving the therapeutic options.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/patologia , Intervalo Livre de Doença , Exantema/induzido quimicamente , Feminino , Humanos , Irinotecano , Estimativa de Kaplan-Meier , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Ann Oncol ; 22(11): 2424-2430, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21385884

RESUMO

BACKGROUND: The aim of this phase II study was to assess the activity of panitumumab in combination with oxaliplatin, 5-fluorouracil, and external radiotherapy (RT) as preoperative treatment in locally advanced rectal cancer patients. PATIENTS AND METHODS: Patients had rectal adenocarcinoma, cT3N+ or cT4N-/+ stage, located <12 cm from the anal margin. Panitumumab was administered before the start of chemo-RT, and every 2 weeks in combination with 5-fluorouracil-oxaliplatin with concurrent RT. Rectal surgery was carried out 7-8 weeks after the end of neoadjuvant treatment. The primary end point was a pathological complete response rate of 25%. RESULTS: Sixty patients were enrolled from February 2007 to October 2009. Fifty-five (91.7%) patients underwent surgery. Rate of pathological complete response was 21.1% (95% confidence interval 10.4% to 31.6%). Pathological downstaging occurred in 33 of 57 (57.9%) patients. Grade 3-4 toxicity during neoadjuvant treatment was diarrhea (38.9%), cutaneous reactions (18.6%), nausea (5.1%), asthenia (3.4%), anorexia (3.4%), and neutropenia (1.7%). One toxic death was observed for diarrhea. CONCLUSIONS: In our study, the primary end point is not reached and panitumumab combination treatment was associated with high incidence of grade 3-4 diarrhea. The higher pathological complete response rate in comparison with the results of previous neoadjuvant rectal cancer trials with anti-epidermal growth factor receptor monoclonal antibodies supports further studies necessary to understand the possibility of optimal regimens and sequences with chemo-RT.


Assuntos
Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/radioterapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Retais/tratamento farmacológico , Neoplasias Retais/radioterapia , Adenocarcinoma/cirurgia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Biomarcadores Tumorais/genética , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Terapia Neoadjuvante , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Panitumumabe , Tomografia por Emissão de Pósitrons , Cuidados Pré-Operatórios , Neoplasias Retais/genética , Neoplasias Retais/cirurgia
12.
Br J Cancer ; 103(10): 1542-7, 2010 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-20959822

RESUMO

BACKGROUND: We assessed the effectiveness of cetuximab plus chronomodulated irinotecan, 5-fluorouracil (5-FU), leucovorin (FA) and oxaliplatin (L-OHP) (chrono-IFLO) administered as neoadjuvant chemotherapy to increase the resectability of colorectal liver metastases. METHODS: This was a phase II prospective trial with rate of liver metastases resection as primary end point. Forty-three patients with unresectable metastases were enroled: 9 with metastases >5 cm; 29 with multinodular (>4) disease; 1 with hilar location; 4 with extrahepatic lung disease. Treatment consisted of cetuximab at day 1 plus chronomodulated irinotecan 5-FU, FA and L-OHP for 2-6 days every 2 weeks. After the first 17 patients, doses were reduced for irinotecan to 110 mg m⁻², 5-FU to 550 mg m⁻² per day and L-OHP to 15 mg m⁻² per day. RESULTS: Macroscopically complete resections were performed in 26 out of 43 patients (60%) after a median of 6 (range 3-15) cycles. Partial response was noticed in 34 patients (79%). Median overall survival was 37 months (95% CI: 21-53 months), with a 2-year survival of 68% in the entire population, 80.6% in resected patients and 47.1% in unresected patients (P=0.01). Grade 3/4 diarrhoea occurred in 93% and 36% of patients before and after dose reduction. CONCLUSION: Cetuximab plus chrono-IFLO achieved 60% complete resectability of colorectal liver metastases.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Neoplasias Hepáticas/patologia , Terapia Neoadjuvante/métodos , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Cetuximab , Neoplasias Colorretais/mortalidade , Neoplasias Colorretais/cirurgia , Diarreia/induzido quimicamente , Intervalo Livre de Doença , Receptores ErbB/metabolismo , Feminino , Fluoruracila/administração & dosagem , Hepatectomia , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Projetos de Pesquisa , Taxa de Sobrevida , Tomografia Computadorizada por Raios X
13.
Eur J Cancer ; 44(9): 1217-22, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18424032

RESUMO

Young people (40 years of age) with colorectal cancer (CRC) represent a distinct subgroup with more aggressive disease behaviour compared to older patients. We evaluate whether p53 and bcl-2 could be useful in identifying young patients at higher risk of tumour progression. We reviewed 1340 CRC patients with 58 patients 40 years (4.2%). They had more frequent moderately or poorly differentiated mucinous adenocarcinomas (26% versus 12.3%, p=0.03); higher advanced stage at diagnosis; shorter 5-year overall survival (49.8% versus 71%; p=0.02); more frequent p53 positive (89.8% versus 72.6%, p<0.05) and bcl-2 negative (88.0% versus 66.2%, p<0.05) tumours; no difference in DNA content or proliferation indexes. Moreover, p53+ and bcl-2- resulted in being independent predictors of survival with shorter survival for the p53+/bcl-2- patients. Combining p53 and bcl-2, we could identify young CRC patients at higher risk of progression, who probably require development of a more sophisticated therapeutic approach based on identification of predictive factors.


Assuntos
Neoplasias Colorretais/mortalidade , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Adulto , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Apoptose/fisiologia , Transformação Celular Neoplásica/patologia , Distribuição de Qui-Quadrado , Neoplasias Colorretais/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Antígeno Ki-67/metabolismo , Masculino , Pessoa de Meia-Idade
14.
In Vivo ; 20(6A): 711-4, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17203751

RESUMO

BACKGROUND: In patients locally progressing after two lines of chemotherapy, some locoregional approaches showed encouraging results in terms of local control of disease. The aim of our study was to evaluate toxicity, clinical response and quality of life in 48 patients with unresectable colorectal liver metastases submitted to selective internal radiotherapy (SIRT). MATERIALS AND METHODS: Up to now 35 patients with unresectable colorectal liver metastases, refractory to two lines of chemotherapy, underwent intra-arterial infusion of resin microspheres with yttrium-90 (SIR-spheres). Pre-treatment evaluation included a CT scan, blood tests, a PET scan and arteriography of celiac trunk, hepatic and superior mesenteric artery; extrahepatic uptakes and pulmonary shunts more than 10% were excluded by a Scinti-scan. The gastroduodenal artery was embolized before the SIR-spheres injection. Other exclusion criteria were liver dysfunction and anatomical vascular anomalies. The clinical response was evaluated by CT-scan following the RECIST criteria. Median follow-up was 4 months. RESULTS: Median number of metastases was 4 (range, 1-15), 38% of cases presenting hepatic involvement < 25%. The median SIRT dose delivered was 1.7 GBq. Median pulmonary shunt was 6%. No operative mortality occurred; early toxicity (within 48 hours) was 20.6%, shown as fever, acute pain and leucocytosis. The late toxicity was 24.1% with chronic pain, jaundice and nausea being the most frequent. All the toxic events were graded 2 or 3 according to the WHO scale. Preliminary results were available in terms of clinical response after 6 weeks: 12.5% had a partial response, 75% a stable disease, while progression of disease, was observed in 12.5% of the patients. CONCLUSION: SIRT is a safe treatment in terms of acute and late toxicity. Intra-arterial microspheres could represent a good therapeutic option for patients with progressing liver metastases only, after two lines of systemic chemotherapy.


Assuntos
Neoplasias Colorretais/radioterapia , Neoplasias Hepáticas/radioterapia , Neoplasias Hepáticas/secundário , Radioisótopos de Ítrio/administração & dosagem , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/patologia , Progressão da Doença , Humanos , Infusões Intra-Arteriais , Microesferas , Estudos Prospectivos , Qualidade de Vida , Dosagem Radioterapêutica , Fatores de Tempo , Resultado do Tratamento , Radioisótopos de Ítrio/efeitos adversos
15.
J Exp Clin Cancer Res ; 23(2): 207-13, 2004 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-15354404

RESUMO

This retrospective study compared toxicity and activity of vinorelbine according to two schedules with different projected dose intensities in heavily pretreated breast cancer patients. Forty patients were assessable for toxicity and activity in each group; group A received vinorelbine 25 mg/m2 week + lenograstim (150 microg/m2 s.c. on day 3); group B received 25 mg/m2 on days 1 and 8 every 3 weeks. The projected dose intensity was 25 mg/m2/week and 16.6 mg/m2/week, and delivered dose intensity 95.2% and 94.5% in group A and B, respectively. Grade 3-4 afebrile neutropenia was recorded in 25% and 37.5% of patients in A and B, respectively. Overall response rate, 52.5% and 35%; no change, 35% and 40%; progression of disease, 12.5% and 25% in A and B, respectively. Median duration of the response was 10 months for group A and 7 months for B. Median time to progression: 9.0 months and 4.0 months for A and B, respectively. At a median follow-up of 45 months for group A and 19 months for group B, median overall survival was 19 months and 16, respectively. In conclusion the results of the study showed that dose intensity of vinorelbine could have an improvement in terms of time to progression in pretreated advanced breast cancer.


Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Vimblastina/análogos & derivados , Vimblastina/uso terapêutico , Adjuvantes Imunológicos/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Neoplasias da Mama/patologia , Progressão da Doença , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Humanos , Lenograstim , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/secundário , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/secundário , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Estudos Retrospectivos , Terapia de Salvação , Fatores de Tempo , Vinorelbina
16.
J Chemother ; 16 Suppl 5: 11-4, 2004 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-15675468

RESUMO

Rectal adenocarcinomas is usually associated to a poorer outcome than colon cancers. In this study we analyzed the impact on overall survival of p53 and Bcl-2, evaluated by immunohistochemical techniques, in 126 advanced rectal cancer patients submitted to 5 fluorouracil based adjuvant therapy. Shorter overall survival was observed in patients bearing p53 positive and Bcl-2 negative tumors, although in multivariate analysis only p53 emerged as independent predictor of a worse outcome. These results seem to indicate that, in stage III-IV rectal cancer, p53 alterations may identify high risk patients to be enrolled in more aggressive and/or innovative adjuvant/neoadjuvant treatments.


Assuntos
Proteínas Proto-Oncogênicas c-bcl-2/análise , Neoplasias Retais/terapia , Proteína Supressora de Tumor p53/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Retais/química , Neoplasias Retais/mortalidade , Taxa de Sobrevida
17.
Br J Cancer ; 89(10): 1870-5, 2003 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-14612895

RESUMO

The combination of irinotecan (CPT-11), oxaliplatin (L-OHP), 5-fluorouracil (5-FU) and folinic acid (FA) is one of the possibilities to overcome chemoresistance in advanced colorectal cancer (ACRC) patients. The aim of this study was to determine the tolerability and activity of CPT-11 plus chronomodulated infusion of L-OHP, 5-FU and FA in ACRC patients. A total of 35 patients (91% pretreated, 77% with CPT-11, 54% with L-OHP, 42% with both) were treated every 3 weeks with CPT-11, 180 mg m(-2) day 1 i.v., plus L-OHP, 20 mg m(-2) day(-1), 5-FU, 700 mg m(-2) day(-1) and FA, 150 mg m(-2) day(-1), all three drugs from day 2 to day 5 by chronomodulated infusion. The patients' (pt) data were as follows: male/female 21/14; median age 58 years (range: 38-70); PS 0: 26 pts (74%), PS 1: 8 pts (23%), PS 2: 1 pt (3%); primary tumour colon/rectum 26/9; involved organs: 1, 14 pts (40%); 2, 17 pts (48%); >or=3: 4 pts (11%); previous chemotherapy lines 1: 12 pts (34%), 2: 10 pts (28%), >or=3: 10 pts (28%). A total of 221 courses (c) were performed; no grade 4 toxicity was observed with only one grade 3 (G3) neutropenia and thrombocytopenia (3%) in one out of 221 courses (<1%). Maximal toxicity (G3) was nausea and diarrhoea in 10 pts (28%), occurring in 14 out of 221 c (6%) and 12 out of 221 c (5%) respectively. Seven patients achieved a partial response (20%, confidence interval (c.i.) 6.8-33.3) and one patient a complete response (2.9%, c.i. 0-8.4), for a total overall response rate of 22.9% (c.i. 9-36.8); 15 out of 35 (42.9%, c.i. 26.5-59.3) had stable disease and 12 out of 35 (34.3%, c.i. 18.6-50) patients underwent a progression. In conclusion, this four-drug regimen is feasible in advanced pretreated ACRC patients with no significant haematological toxicity and acceptable diarrhoea. The activity of this combination is currently studied in EORTC 05011 study.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Cronoterapia , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Neoplasias Colorretais/patologia , Progressão da Doença , Feminino , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Oxaliplatina , Resultado do Tratamento
19.
J Exp Clin Cancer Res ; 22(4 Suppl): 197-202, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16767931

RESUMO

Hepatic metastases represent one of major clinical problems in patients affected by solid tumours because liver is the first site of metastatic disease after lymph nodes, (1, 2). The most common origins among adults are from colon and rectum cancer followed by pancreas (adenocarcinoma or neuroendocrine), lung and breast (3-7). It is estimated that in 15-20% of patients affected by adenocarcinoma of colon-rectum liver metastases are present at the time of diagnosis (8-11), while in 40% of cases they will develop during the follow-up (10, 11). Liver metastases are the first determinant for survival (1, 3, 12-17), and both hepatic and extrahepatic involvement have a statistical significant impact on it (3, 14, 18-21). Prognosis of patients affected by untreated disease is very poor, being 5 to 14 months with rare 2-year survivors and a 5-year survival rate of 0% (10, 21-24). In half of all patients affected by colorectal cancer and undergoing to a radical surgery, disease will fail in the liver (8, 25-28); among patients dying for colorectal cancer, 60-70% have a liver involvement (9, 29), and in 20-25% liver is the only site of recurrence and death results from liver failure (3, 29-31). In Autoptic studies those rates increased up to 83% and 38% respectively (1, 10, 17, 32).


Assuntos
Adenocarcinoma/secundário , Adenocarcinoma/terapia , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/terapia , Adenocarcinoma/mortalidade , Ablação por Cateter , Terapia Combinada , Criocirurgia , Humanos , Neoplasias Hepáticas/mortalidade , Terapia Neoadjuvante , Prognóstico , Análise de Sobrevida , Taxa de Sobrevida
20.
J Exp Clin Cancer Res ; 22(4 Suppl): 213-7, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16767934

RESUMO

UNLABELLED: Diagnosed colorectal cancer patients presents liver metastases at presentation in 25% of cases, an another 25% of patients will develop hepatic recurrence during follow-up period. Natural history of disease in untreated patients is sad without long term survivors. The only chance of curative treatment is surgical resection. Aim of this study was to evaluate recurrence and survival in the multimodal approach of colorectal liver metastases patients. MATERIALS: From 1990 to 2003, 212 colorectal cancer liver metastases patients were observed at the "Regina Elena" cancer institute of Rome, the 48.8% of cases were synchronous. Of 185 patients with minimum follow-up of 12 months, 80 were surgically resected, while 105 were not. Major resection was possible in 45.3% of cases and 66.1% of them were radicals. Tweny were treated by surgery alone, 65% were resected after i.v. chemotherapy, in the last 10% resection followed HAI chemotherapy. Of non resected patients, in the 36.2% i.v. chemotherapy was administered, 26.1% were submitted to HAI chemotherapy, in 18.9% others treatments were carried out and 18.8 were untreated. RESULTS: Operative mortality was contained to 2.5%. The hepatic recurrence was observed in 50.5% of cases while extrahepatic was in the 13.6%. In the resected cases the 5-yr. Overall survival was 38.8%, the disease-free survival decreased to 14.7% with a median time to progression of 15 months. The liver recurrence-free survival was 31.3%. Really bad prognopsis was observed in the non resected patients with none survived at 5 years and 3-yr overall survival of 18.7%. CONCLUSION: In selected patients the multimodality approach to treatment of hepatic metastases showed satisfactory results in terms of local and distal control of disease. Long term survivors were observed in the our experience.


Assuntos
Adenocarcinoma/secundário , Neoplasias Colorretais/patologia , Neoplasias Hepáticas/secundário , Adenocarcinoma/mortalidade , Adenocarcinoma/terapia , Antineoplásicos/uso terapêutico , Neoplasias Colorretais/mortalidade , Terapia Combinada , Procedimentos Cirúrgicos do Sistema Digestório , Intervalo Livre de Doença , Humanos , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/terapia , Recidiva Local de Neoplasia/epidemiologia , Análise de Sobrevida , Taxa de Sobrevida
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