RESUMO
BACKGROUND: High-dose chemotherapy (HDC) and autologous stem cell transplantation (ASCT) are feasible and effective salvage treatments for human immunodeficiency virus (HIV)-related relapse or refractory lymphoma. Among the main concerns with ASCT in HIV-infected persons is the additional immune depletion caused by treatment, which could amplify the preexisting immune deficit. The aims of our study were to assess the impact of conventional chemotherapy before salvage treatment was administered, in this population, and to evaluate immune reconstitution dynamics during ASCT. METHODS: All 33 HIV-infected and HIV-uninfected patients who underwent comparable ASCT protocols at the National Cancer Institute (Aviano, Italy) who underwent 1 month of follow-up after transplantation were included in a prospective immunological study. Demographic, clinical, and immunovirological data were obtained before administration of induction therapy, during transplantation, and at 24 months of follow-up. RESULTS: Before HDC, no significant differences were observed in CD4(+) cell subsets and signal joint T cell receptor excision circles (sjTRECs), although HIV-infected persons had inverted ratios of CD4(+) cells to CD8(+) cells because they had higher CD8(+) T cell counts, compared with HIV-uninfected persons. After ASCT, this inversion was also observed in HIV-uninfected patients up to 24 months. CD4(+) cell subsets had similar recoveries, with a temporary setback in HIV-infected persons 3 months after reinfusion, together with an increase in infections. sjTRECs demonstrated similar dynamics in both populations and serve as a useful predictive marker of recovery of CD4(+) cell subsets. No significant changes emerged in HIV DNA levels during the follow-up period, with values at 24 months significantly lower than those at baseline. CONCLUSIONS: Our study demonstrated that ASCT in HIV-infected persons with lymphoma does not worsen the initial immune impairment and does not enhance viral replication or the peripheral HIV reservoir in the long term.
Assuntos
Infecções por HIV/complicações , Linfoma/terapia , Transplante de Células-Tronco , Adulto , Antineoplásicos/uso terapêutico , Contagem de Linfócito CD4 , Feminino , Infecções por HIV/imunologia , Humanos , Sistema Imunitário/efeitos dos fármacos , Linfoma/tratamento farmacológico , Linfoma/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva , Regeneração , Terapia de Salvação , Timo/fisiologia , Transplante Autólogo , Carga ViralRESUMO
UNLABELLED: Several drugs have been approved for the treatment of patients affected by advanced non-small cell lung cancer (NSCLC) in progression after first line chemotherapy: Docetaxel, Pemetrexed and Erlotinib. Poor gain of survival has been demonstrated in randomised trials and patient characteristics predicting activity are poorly known yet. We evaluated the activity and toxicity of Pemetrexed, in a post-registration phase, to assess whether clinical benefits justify its employment in a second-line setting in routine clinical practice. PATIENTS AND METHODS: We collected data on patients with advanced NSCLC treated with Pemetrexed 500mg/m(2) every 21 days, after progression to prior chemotherapy. RESULTS: One hundred and sixty patients from 4 different Italian Institutions, treated with Pemetrexed, mostly as second-line therapy, were analysed. There was a predominance of males versus females, adenocarcinoma versus other histologies; the median age was 63.6 years. The toxicity profile was extremely mild and the response rate (11.2% patients in complete or partial response) was similar to previous reports from the literature. The median overall survival, 12 months, was better than previously reported. CONCLUSION: Improved efficacy and mild toxicity observed in this clinically relevant patient population confirms Pemetrexed as an interesting choice in second-line treatment of NSCLC. Patient characteristics alone are not able to predict response to Pemetrexed.
Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Glutamatos/uso terapêutico , Guanina/análogos & derivados , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Carcinoma Pulmonar de Células não Pequenas/patologia , Intervalo Livre de Doença , Feminino , Guanina/uso terapêutico , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Pemetrexede , Estudos RetrospectivosRESUMO
BACKGROUND: The quantitative evaluation of human herpesvirus 8 (HHV8) DNA is not well described in the clinical management of HHV8-related lymphoproliferative diseases. OBJECTIVES: To evaluate and to compare HHV8 viral load in different blood compartments from patients with multicentric Castleman's disease (MCD), primary effusion lymphoma (PEL) and HHV8-associated solid lymphoma (SLY) and to establish which clinical sample would be preferable for HHV8 DNA testing. STUDY DESIGN: We assessed HHV8 DNA in plasma and peripheral blood mononuclear cells (PBMCs) paired samples from 7 PEL, 8 MCD, 2 SLY HIV+ patients at the diagnosis and during the course of the illness by using a real time PCR assay. RESULTS: HHV8 viremia was always detectable at diagnosis. HHV8 DNA levels were correlated in matched pairs of samples at diagnosis and during follow-up (Spearman correlation coefficient: r=0.83, p<0.001 and r=0.73, p<0.001, respectively). The performance characteristics of the PCR assay with both materials did not show disparity by the analysis of the receiver operating characteristic (ROC) curve (X(1)(2)=0.50; p=0.48). CONCLUSIONS: Plasma or PBMCs are both adequate samples for HHV8 DNA quantification and Real time PCR provides a reliable method to estimate viral replication in patients with HHV8-related lymphoproliferations, where HHV8 viral load is a consistent feature.
Assuntos
DNA Viral/sangue , Infecções por Herpesviridae/virologia , Herpesvirus Humano 8/isolamento & purificação , Leucócitos Mononucleares/virologia , Plasma/virologia , Carga Viral , Hiperplasia do Linfonodo Gigante/virologia , Humanos , Linfoma/virologia , Linfoma de Efusão Primária/virologia , Reação em Cadeia da Polimerase/métodos , Curva ROCRESUMO
Colorectal cancers are rare in developing countries, but are the second most frequent malignancy in the affluent world. Data on colorectal cancer in HIV-positive patients are limited. Up to now, there are no published data on treatment patterns, response to therapy, or survival in this setting. Oxaliplatin is an antineoplastic agent currently indicated, concomitantly to fluorouracil and leucovorin, for the treatment of advanced colorectal cancer. The FOLFOX-4 regimen (oxaliplatin 85 mg/m(2) as a two-hour infusion on day 1; leucovorin 200 mg/m(2) as a two-hour infusion on days 1 and 2, fluorouracil as a bolus infusion on days 1 and 2, followed by a fluorouracil 22-hour infusion 600 mg/m(2) for two consecutive days every two weeks), with concomitant highly active antiretroviral therapy (HAART) is feasible and active, while the HIV infection is not a limiting factor for its use. Moreover, the concomitant use of HAART does not seem to increase the toxicity of the FOLFOX-4 regimen.
Assuntos
Adenocarcinoma/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Adenocarcinoma/complicações , Adenocarcinoma/patologia , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Terapia Antirretroviral de Alta Atividade , Neoplasias Colorretais/complicações , Neoplasias Colorretais/patologia , Feminino , Fluoruracila/administração & dosagem , Infecções por HIV/complicações , Humanos , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Compostos Organoplatínicos/administração & dosagem , Resultado do TratamentoRESUMO
BACKGROUND: In the era of highly active antiretroviral therapy (HAART), malignancies are the primary cause of increased mortality in patients with human immunodeficiency virus (HIV) infection, hence representing a new challenge for oncologists. To date, there is little evidence in the English literature about chemotherapy treatment in HIV-positive patients with metastatic colorectal cancer. CASE REPORT: We describe the case of an HIV-positive 48-year-old male patient with metastatic colorectal cancer, treated with a bevacizumab, irinotecan, fluorouracil, and leucovorin regimen, with concomitant HAART. No opportunistic infections and grade 3-4 haematological and non-haematological toxicity were reported. The HIV infection was kept under control during the bevacizumab chemotherapy treatment. CONCLUSIONS: This case suggests that, in the HAART era, the best multidisciplinary approaches can be offered to HIV-positive patients with metastatic colorectal cancer, who have a good performance status and a well controlled HIV infection. An HIV infection should not preclude the use of the best available chemotherapy treatment in this particular group of patients, including targeted/biological drugs.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/secundário , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/métodos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Neoplasias Colorretais/complicações , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Leucovorina/administração & dosagem , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is an increasing cause of mortality in human immunodeficiency virus (HIV) seropositive patients. Concurrent infection with HIV may accelerate the progression from cirrhosis to HCC. Viral hepatitis and alcohol abuse are the main risk factors for HCC in developed countries. Exposure to these risk factors is common among HIV-infected patients. We report the case of a 43-year-old woman affected by HCC, with unusual soft tissue metastases (left masseter muscle) and HIV/HCV coinfection. The usual route of metastatic spread from classic HCC is hematogenous, with the most common extrahepatic site being the lung. Our case, besides the unusual distant metastatic site, showed very rapid clinical progression, as has been commonly observed in HIV-infected patients with HCC. The case series of HCC in HIV-positive individuals published to date does not cumulatively exceed 70 subjects.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/complicações , Carcinoma Hepatocelular/diagnóstico , Hepatite C/complicações , Neoplasias Hepáticas/diagnóstico , Adulto , Terapia Antirretroviral de Alta Atividade , Carcinoma Hepatocelular/virologia , Progressão da Doença , Neoplasias Faciais/complicações , Neoplasias Faciais/diagnóstico , Dor Facial/etiologia , Evolução Fatal , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Neoplasias Hepáticas/virologia , Imageamento por Ressonância Magnética , Músculo Masseter , Neoplasias de Tecido Muscular/complicações , Neoplasias de Tecido Muscular/diagnóstico , Fatores de RiscoRESUMO
Fourteen HIV-infected patients with advanced Kaposi's sarcoma (KS) received Irinotecan 150 mg/m intravenously on days 1 and 10. All patients were relapsed/progressed during highly active antiretroviral therapy, administered as primary antineoplastic therapy. An objective response, all partial remissions, occurred in 75% of patients. Irinotecan was well tolerated, severe leukopenia occurred in only 33% of patients. In HIV-infected patients with advanced KS, irinotecan is active and well tolerated.
Assuntos
Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/análogos & derivados , Infecções por HIV/complicações , Sarcoma de Kaposi/tratamento farmacológico , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Camptotecina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Doenças Hematológicas/induzido quimicamente , Humanos , Irinotecano , Masculino , Pessoa de Meia-Idade , Sarcoma de Kaposi/complicações , Resultado do TratamentoRESUMO
BACKGROUND: Primary effusion lymphoma (PEL) represents a peculiar lymphoma infected with human herpesvirus 8 (HHV-8) and occurs predominantly in human immunodeficiency virus (HIV)-infected patients. The aim of the present study was to evaluate the immunologic and virological parameters, including HHV-8 viremia, of 5 HIV-infected patients with PEL whose disease was diagnosed and treated at our institute. METHODS: Five patients were enrolled in the study. Biological parameters, such as latent and lytic HHV-8 antigen levels, plasma HHV-8 load, Epstein-Barr virus plasma DNA load, HIV-1 load, and CD4 cell count, were assessed before treatment, during therapy, and at follow-up. RESULTS: Four patients were treated with chemotherapy and highly active antiretroviral therapy (HAART), and 1 was treated with HAART alone; 3 of 5 patients reached complete remission. HHV-8 could be detected before the initiation of therapy in plasma from all patients analyzed. HHV-8 levels decreased after therapy in 4 patients. During the whole observation period, plasma HHV-8 load showed a statistically significant inverse correlation with CD4 cell count but no significant correlation with HIV load and response to therapy. CONCLUSIONS: Our analysis demonstrates that HHV-8 can be detected in the plasma at the onset of PEL; its prognostic role needs to be explored. CD4 cell count seems to be the most important indicator of progression of PEL.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/imunologia , Infecções por HIV/virologia , Linfoma não Hodgkin/etiologia , Adulto , Fármacos Anti-HIV , Contagem de Linfócito CD4 , Progressão da Doença , Feminino , Regulação Viral da Expressão Gênica , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Herpesvirus Humano 8 , Humanos , Linfoma não Hodgkin/virologia , Masculino , Carga Viral , Proteínas Virais/metabolismo , ViremiaRESUMO
To assess the impact of highly active antiretroviral therapy (HAART) on the outcome of systemic human immunodeficiency virus-related non-Hodgkin lymphoma (HIV-NHL), we retrospectively analyzed 235 patients in whom HIV-NHL was diagnosed from April 1988 through December 1999. A multivariate Cox proportional hazards model was used to estimate prognostic factors for overall survival (OS), progression-free survival (PFS), and disease-free survival (DFS). Complete remission occurred in 49% of patients, and the 3-year rates of OS, PFS, and DFS were 19%, 49%, and 73%, respectively. The greatest risk for shortened OS, PFS, and DFS was associated with no HAART use (compared with long-term HAART use); hazard ratios were 17.42 (95% confidence interval [CI], 17.42-40.25), 9.11 (95% CI, 3.71-22.32), and 8.54 (95% CI, 1.19-61.11), respectively. Our study suggests that the long-term use of HAART may favorably change the outcome for patients with systemic HIV-NHL.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/complicações , Linfoma Relacionado a AIDS/mortalidade , Linfoma não Hodgkin/mortalidade , Avaliação de Resultados em Cuidados de Saúde , Adulto , Contagem de Linfócito CD4 , Estudos de Coortes , Feminino , HIV , Humanos , Linfoma não Hodgkin/etiologia , Masculino , PrognósticoRESUMO
We evaluated the replication and resistance patterns of human immunodeficiency virus (HIV) strains recovered from HIV-infected patients with non-Hodgkin lymphoma (NHL) who were receiving chemotherapy (CT) concomitant with highly active antiretroviral therapy (HAART). We analyzed virological response to HAART in 35 patients with HIV and NHL who were treated with a cyclophosphamide-doxorubicin-vincristine-prednisone chemotherapy regimen and HAART and the virological response in 26 HIV-infected patients with CD20 cell-positive NHL who were treated with rituximab and cyclophosphamide-doxorubin-etoposide therapy. Genotype and virtual phenotype analyses were performed at baseline and when virological failure occurred. Only 9 patients met the criteria for virological failure. Genotype and virtual phenotype analyses demonstrated that, during CT administration, new mutations might occur, but there were no significant changes in the preexisting resistance patterns. Our data show that combination therapy consisting of CT and HAART is feasible and that the virological response can be maintained in the majority of patients receiving this treatment.
Assuntos
Fármacos Anti-HIV/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Ciclofosfamida/uso terapêutico , Doxorrubicina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Linfoma não Hodgkin/tratamento farmacológico , Prednisona/uso terapêutico , Vincristina/uso terapêutico , Viremia/tratamento farmacológico , Adolescente , Adulto , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Terapia Antirretroviral de Alta Atividade , Criança , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Humanos , Linfoma não Hodgkin/complicações , Masculino , Pessoa de Meia-Idade , Rituximab , Carga Viral , Viremia/complicaçõesRESUMO
PURPOSE: To determine whether abagovomab maintenance therapy prolongs recurrence-free (RFS) and overall survival (OS) in patients with ovarian cancer in first clinical remission. PATIENTS AND METHODS: Patients with International Federation of Gynecology and Obstetrics stage III to IV ovarian cancer in complete clinical remission after primary surgery and platinum- and taxane-based chemotherapy were randomly assigned at a ratio of 2:1 in a phase III, double-blind, placebo-controlled, multicenter study. Abagovomab 2 mg or placebo was administered as 1-mL suspension once every 2 weeks for 6 weeks (induction phase) and then once every 4 weeks (maintenance phase) until recurrence or up to 21 months after random assignment of the last patient. The primary end point was RFS; secondary end points were OS and immunologic response. RESULTS: Characteristics of the 888 patients included: mean age, 56.3 years; Eastern Cooperative Oncology Group performance status, ≤ 1 in > 99% of patients; serous papillary subtype, 81.5%; stage III, 85.9%; and cancer antigen 125 ≤ 35 U/mL after third cycle, 80.9%. Mean exposure to study treatment (± standard deviation) was 449.7 ± 333.08 days. Hazard ratio (HR) of RFS for the treatment group using tumor size categorization (≤ 1 cm, > 1 cm) was 1.099 (95% CI, 0.919 to 1.315; P = .301). HR of OS using tumor size categorization (≤ 1 cm, > 1 cm) was 1.150 (95% CI, 0.872 to 1.518; P = .322). The most frequently reported type of adverse event was an injection site reaction in 445 patients (50.2%), followed by injection site erythema and fatigue in 227 (25.6%) and 212 patients (23.9%), respectively. By the final visit, median anti-anti-idiotypic antibody level was 493,000.0 ng/mL, indicating a robust response. CONCLUSION: Abagovomab administered as repeated monthly injections is safe and induces a measurable immune response. Administration as maintenance therapy for patients with ovarian cancer in first remission does not prolong RFS or OS.
Assuntos
Adenocarcinoma Mucinoso/tratamento farmacológico , Anticorpos Monoclonais/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Cistadenocarcinoma Seroso/tratamento farmacológico , Neoplasias do Endométrio/tratamento farmacológico , Neoplasias Epiteliais e Glandulares/tratamento farmacológico , Neoplasias Ovarianas/tratamento farmacológico , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Anticorpos Monoclonais Murinos , Carcinoma Epitelial do Ovário , Cistadenocarcinoma Seroso/mortalidade , Cistadenocarcinoma Seroso/patologia , Método Duplo-Cego , Neoplasias do Endométrio/mortalidade , Neoplasias do Endométrio/patologia , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Neoplasias Epiteliais e Glandulares/mortalidade , Neoplasias Epiteliais e Glandulares/patologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Prognóstico , Taxa de SobrevidaAssuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Quinazolinas/uso terapêutico , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/patologia , Feminino , Gefitinibe , Humanos , Neoplasias Pulmonares/patologia , Masculino , Estadiamento de NeoplasiasRESUMO
Ovarian cancer has the highest mortality rate among gynaecological tumours despite the fact that the majority of patients with advanced disease achieve complete remission after first-line surgery and chemotherapy. Unfortunately, disease recurrence occurs in the majority of patients and second-line treatments are not curative. Clearly, the persistence of dormant and drug-resistant cells after front-line treatments results in the inability to cure the disease. The identification of cancer-initiating cells or cancer stem cells as key players in the development of recurrence has opened up a novel field of research aimed at identifying additional innovative therapeutic approaches. Strategies of maintenance therapy to extend the survival of patients have been studied, but to date no overall survival benefit has been detected. Currently, numerous clinical trials have just been completed or are ongoing involving patients achieving a complete clinical response after first-line chemotherapy in order to evaluate the efficacy of different therapeutic approaches in terms of disease-free survival and overall survival. At the 2010 ASCO meeting, the first positive results of a phase III clinical trial in this setting were presented: bevacizumab (15 mg/kg i.v. every 21 days) added to first-line chemotherapy and continued for an additional 15 cycles was found to prolong progression-free survival of 3.8 months in comparison to 6 cycles of chemotherapy alone or only 6 cycles of chemotherapy plus bevacizumab. In addition, positive results were announced for a second phase III trial testing bevacizumab in the same setting, but at half dose. The final assessment of the overall clinical benefit and the approval of bevacizumab in maintenance therapy by regulatory agencies is expected to be positive, as are the final results of abagovomab phase III trial MIMOSA, another antibody-based therapy tested as a maintenance treatment for advanced ovarian cancer patients. Encouraging preliminary results confirming the safety profile and the immunogenic activity of abagovomab were presented at the last ASCO meeting. The final results are expected to be released in the first half of 2011.
RESUMO
INTRODUCTION: Ovarian cancer (OC) is the fifth most common cancer in women. Unfortunately, more than 70% of cases are detected at an advanced stage with a risk of recurrence, after front line therapy, of over 75%. The need for new therapeutic strategies is extremely high. AREAS COVERED: The development status and the possible role of specific immunotherapy of abagovomab are discussed in the context of the possible therapeutic options for maintenance therapy in advanced OC. An overview of abagovomab, generation and mechanism of action, Phase I/II results and the status of the Phase II/III ongoing trial is given. EXPERT OPINION: Abagovomab stimulates the humoral immune response and the cell-mediated immune response in the studies conducted to date. In the proof of concept (POC) study abagovomab prolonged overall survival in those OC recurrent patients who showed an immune response. Abagovomab has an excellent safety and tolerability profile. These characteristics make abagovomab an optimal candidate for a maintenance treatment for OC patients after frontline therapy. The final results of the Phase II/III pivotal study evaluating abagovomab in this setting will be available in the first half of 2011.
Assuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Animais , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Murinos , Antineoplásicos/efeitos adversos , Medicina Baseada em Evidências , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Recidiva Local de Neoplasia , Neoplasias Ovarianas/imunologia , Neoplasias Ovarianas/mortalidade , Neoplasias Ovarianas/patologia , Fatores de Tempo , Resultado do TratamentoRESUMO
The aim of this study was to look for the maximum tolerated dose (MTD) of gemcitabine and 5-fluorouracil in a new regimen also containing the antiangiogenic bevacizumab and immunotherapy (IT) for the treatment of metastatic renal cell cancer. The primary objective of this multicenter dose-finding study was to establish the MTD of chemotherapy (CT) in combination with fixed doses of IT and bevacizumab. The secondary objective was to assess the combination's activity. Five escalated dose levels of CT with intravenous gemcitabine and 5-fluorouracil (days 1 and 8 every 28 d), were associated together with intravenous bevacizumab (10 mg/kg on days 1 and 15 every 28 d), subcutaneous interleukin-2 (1 MIU/m² bid on days 8, 9, 15, 16, and 1 MIU/m²/d on days 10-12 and 17-19), and interferon-α-2a (3 MIU on days 10, 12, 17, 19). Of the 27 enrolled patients, 59% had been pretreated. The MTD was not reached. The highest CT dose studied was gemcitabine 1000 mg/m² and 5-fluorouracil 600 mg/m². More frequent grade 3 to 4 toxicities included neutropenia (63%), thrombocytopenia (33%), and fever (26%). The response rate was 33% according to the Response Evaluation Criteria in Solid Tumors. This is the first study that explored the feasibility and safety of combined bevacizumab, IT, and CT in metastatic renal cell cancer. The activity of this regimen is interesting and its efficacy warrants further trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Carcinoma de Células Renais/imunologia , Imunoterapia , Neoplasias Renais/imunologia , Adulto , Idoso , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Bevacizumab , Carcinoma de Células Renais/tratamento farmacológico , Carcinoma de Células Renais/mortalidade , Carcinoma de Células Renais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Análise de Intenção de Tratamento , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Itália , Neoplasias Renais/tratamento farmacológico , Neoplasias Renais/mortalidade , Neoplasias Renais/patologia , Masculino , Dose Máxima Tolerável , Oncologia , Pessoa de Meia-Idade , Metástase Neoplásica , Análise de Sobrevida , GencitabinaRESUMO
The kinetics and predictive value of HIV-1 DNA (HIV DNA) levels in relapsed or refractory HIV lymphoma patients, treated with high-dose chemotherapy (HDC) followed by autologous stem cell transplantation (ASCT), were investigated. HIV DNA was measured by real-time PCR in the peripheral blood mononuclear cells (PBMCs) of 22 patients observed for a median follow-up of 31.0 months. At baseline, HIV DNA was found to be correlated with HIV-1 RNA (HIV RNA) (r = 0.56), but not with CD4(+) counts (r = -0.10). HIV RNA load was under control for the entire follow-up, while HIV DNA levels were almost always detectable (baseline levels vs. 1 year from ASCT levels, p > 0.05). Baseline HIV DNA levels were significantly different between alive and deceased patients (p = 0.03), and the overall survival (OS) analysis showed that for patients with higher HIV DNA levels at baseline there was a higher and nearly significant risk of death if compared to patients with lower levels (HR, 8.33, 95% CI, 0.99-70.06, p = 0.05). Our study demonstrated that high HIV DNA levels at baseline could predict overall survival after ASCT in one of the largest cohorts of HIV lymphoma patients treated with salvage therapy.
Assuntos
Antineoplásicos/uso terapêutico , DNA Viral/sangue , HIV-1/isolamento & purificação , Linfoma Relacionado a AIDS/mortalidade , Transplante de Células-Tronco , Carga Viral , Adulto , Feminino , Humanos , Leucócitos Mononucleares/virologia , Linfoma Relacionado a AIDS/diagnóstico , Linfoma Relacionado a AIDS/terapia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , PrognósticoRESUMO
The aim of our study was to explore the caregivers' perception of the informational needs of Italian elderly cancer patients at the time of diagnosis. We asked the senior cancer patients naïve for treatments and their caregivers, admitted to our National Cancer Centre, to take a written self-administered questionnaire exploring the patient's information needs and his/her information-seeking behavior. The questionnaire was completed by 112 elderly cancer patients (median age 72 years) and their caregivers (median age 54 years). Patients were mostly affected by genital-urinary (27%) or breast/gynecological (25%) cancer. Caregivers were usually females (71%), daughters/sons (45%) and/or partners (41%). One-third of the senior patients showed a desire to receive extensive information regarding diagnosis and gravity, while 44.6% wanted to know about recovery. Caregivers showed improper recognition of the real needs for information of the their own patients (kappa tests showed unsatisfactory or poor agreement). Caregivers cannot be considered the preferred spokespersons of the oncologist when the patient is elderly or his/her needs for information again remain unmet. Interventions, both to help senior patients express their needs and to improve the patient-to-doctor-to-caregiver communication about cancer diseases, are necessary.
Assuntos
Atitude Frente a Saúde , Cuidadores , Avaliação das Necessidades , Neoplasias/terapia , Idoso , Comunicação , Feminino , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Neoplasias/psicologia , Educação de Pacientes como Assunto , Relações Médico-PacienteRESUMO
The effects of CD34 mobilization with chemotherapy and G-CSF administration were evaluated in 13 HIV-positive patients with relapsed lymphomas and low CD4 counts. After mobilization, CD4+ cells increased significantly while HIV-RNA and integrated HIV-DNA showed no increases. G-CSF led to an increase of CD4+ cells with limited effects on HIV replication.