RESUMO
BACKGROUND: Oxaliplatin and topotecan are novel options for a variety of neoplasms. Topotecan has shown fewer side effects and higher efficacy when given as a continuous i.v. infusion compared to single doses, but this regimen has not yet been combined with oxaliplatin. PATIENTS AND METHODS: This phase I/II trial was designed to establish the dose-limiting toxicity of a combination of oxaliplatin (85-130 mg/m2 on day 1) and a continuous infusion of topotecan (initial 0.9 mg/m2 over 72-120 h). Eligible patients with metastatic colorectal cancer had progressive disease during, or within 12 weeks after, palliative fluoropyrimidine-based chemotherapy or in whom intolerable 5-FU toxicity had developed. RESULTS: The study included 21 patients. Subjectively the treatment was well tolerated but haematological toxicity was observed with the initial treatment schedule of oxaliplatin 85 mg/m2 on day 1 and topotecan 0.9 mg/m2 on days 1-5. Reducing topotecan to 0.9 mg/m2 on days 1-3 resulted also in acceptable haematological toxicity. In patients completing three or more therapy cycles, median progression-free survival was 5 months, and 50% had stable disease or showed a partial response. CONCLUSION: The recommended dose of this combination for further testing is oxaliplatin 85 mg/m2 on day 1 and topotecan 0.9 mg/m2 per day as a continuous infusion on days 1-3.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Idoso , Neoplasias Colorretais/patologia , Progressão da Doença , Resistência a Medicamentos , Feminino , Fluoruracila/uso terapêutico , Humanos , Infusões Intravenosas , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Oxaliplatina , Topotecan/administração & dosagem , Topotecan/efeitos adversosAssuntos
Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Doença de Hodgkin/terapia , Imunização Passiva , Interleucina-2/uso terapêutico , Terapia de Salvação , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Murinos , Antígenos CD20/análise , Antígenos CD20/imunologia , Antígenos de Neoplasias/análise , Antígenos de Neoplasias/imunologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Bleomicina/administração & dosagem , Carmustina/administração & dosagem , Ciclofosfamida/administração & dosagem , Citarabina/administração & dosagem , Dacarbazina/administração & dosagem , Dexametasona/administração & dosagem , Doxorrubicina/administração & dosagem , Resistencia a Medicamentos Antineoplásicos , Etoposídeo/administração & dosagem , Etoposídeo/análogos & derivados , Doença de Hodgkin/tratamento farmacológico , Doença de Hodgkin/imunologia , Doença de Hodgkin/patologia , Humanos , Idarubicina/administração & dosagem , Ifosfamida/administração & dosagem , Interleucina-2/administração & dosagem , Masculino , Melfalan/administração & dosagem , Pessoa de Meia-Idade , Prednisona/administração & dosagem , Procarbazina/administração & dosagem , Indução de Remissão , Rituximab , Vimblastina/administração & dosagem , Vincristina/administração & dosagemAssuntos
Infecções por HIV/terapia , Sarcoma de Kaposi/terapia , Neoplasias Cutâneas/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Contagem de Linfócito CD4/efeitos dos fármacos , Terapia Combinada , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Neoplasias Gastrointestinais/terapia , Infecções por HIV/imunologia , Humanos , Neoplasias Pulmonares/terapia , Masculino , Sarcoma de Kaposi/imunologia , Neoplasias Cutâneas/imunologiaRESUMO
The purpose of this study was to assess the efficacy and safety of pegylated liposomal doxorubicin in combination with cyclophosphamide and dexamethasone (CLAD). In this prospective open-label phase II study, 60 patients with advanced multiple myeloma (MM) received three weekly cycles of CLAD, consisting of cyclophosphamide 200 mg/m2 i.v. d1-4, pegylated liposomal doxorubicin 20 mg/m2 i.v. d1 and dexamethasone 40 mg p.o. d1-4 for a maximum of six cycles in absence of disease progression. Efficacy and toxicity was compared to our immediate historical cohort of 46 patients treated with cyclophosphamide, dexamethasone and conventional doxorubicin (CAD). A total of 239 cycles of CLAD and 209 cycles of CAD, respectively, were given. The objective response rate was 71% (CLAD) and 74% (CAD). Non-cumulative hematological toxicity was predominant in both regimens. It was found that CLAD is an active and well-tolerated treatment regimen for MM. Response rate is comparable to other anthracycline containing regimens like CAD with an advantage in hematological toxicity and lower infectious complications, and a presumed advantage of lower cardiotoxicity.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Doxorrubicina/análogos & derivados , Mieloma Múltiplo/tratamento farmacológico , Polietilenoglicóis/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/efeitos adversos , Ciclofosfamida/uso terapêutico , Dexametasona/efeitos adversos , Dexametasona/uso terapêutico , Doxorrubicina/administração & dosagem , Doxorrubicina/efeitos adversos , Doxorrubicina/uso terapêutico , Avaliação de Medicamentos , Feminino , Humanos , Leucopenia/induzido quimicamente , Masculino , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Polietilenoglicóis/efeitos adversos , Resultado do TratamentoRESUMO
We report the case of a 30-years old HIV-infected woman who suffered from recurrent fever up to 41 degrees C, loss of appetite, loss of 8 kg body weight and swelling of the cervical and inguinal lymph nodes. The diagnostic work-up revealed infection with leishmania in gastric and duodenal biopsies. The parasites were also found in the inguinal lymph nodes and in the bone marrow of the patient. According to patient's history the infection was acquired on a holiday in southern spain. The patient was treated with pentavalent antimony in combination with interferon gamma. Visceral leishmaniosis in immuno-suppressed patients is discussed and therapeutic approaches are described.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Enteropatias Parasitárias/diagnóstico , Leishmaniose Visceral/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Adulto , Gluconato de Antimônio e Sódio/uso terapêutico , Biópsia , Terapia Combinada , Feminino , Mucosa Gástrica/patologia , Humanos , Interferon gama/uso terapêutico , Enteropatias Parasitárias/tratamento farmacológico , Enteropatias Parasitárias/patologia , Mucosa Intestinal/patologia , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/patologiaRESUMO
We report a case of a 46-year-old HIV-infected patient suffering Rhodococcus equi pneumonia and septicaemia. After the failure of an initial antibiotic treatment, the upper lobe of the right lung was resected due to a cavitating pneumonia. After that the patient stabilized for a period of 7 months by administration of a resistogram-adapted combination of tetracycline, erythromycin and clindamycin. Due to the patient's decision, antibiotic treatment was stopped when a cytomegalovirus retinitis was diagnosed. Six weeks later new pulmonary infiltrations were diagnosed and a Rhodococcus equi bacteraemia evolved. The patient died one year after the first diagnosis of the Rhodococcus equi infection. The present case suggests that the infection with Rhodococcus equi in patients with advanced HIV infection demands permanent antibiotic prophylaxis.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico por imagem , Infecções por Actinomycetales/diagnóstico por imagem , Pneumonia Bacteriana/diagnóstico por imagem , Rhodococcus equi , Sepse/diagnóstico por imagem , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Infecções por Actinomycetales/patologia , Infecções por Actinomycetales/terapia , Antibacterianos , Bissexualidade , Terapia Combinada , Quimioterapia Combinada/uso terapêutico , Humanos , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Pneumonectomia , Pneumonia Bacteriana/patologia , Pneumonia Bacteriana/terapia , Recidiva , Sepse/patologia , Sepse/terapia , Tomografia Computadorizada por Raios XRESUMO
Fungal infections, in addition to bacterial and opportunistic infections such as Pneumocystis carinii pneumonia, may evolve in patients with infectious complications due to iatrogenic immunosuppression. Aside from common Candida and Aspergillus species, rare fungi like Mucor must be considered in patients with neutropenia or prolonged impaired T-cell function. Here we report on a patient with a low grade lymphoma who was treated with 2-chlorodeoxyadenosine because of disease progression. After recovery from Pneumocystis carinii pneumonia he presented again with clinical signs of pneumonia. No pathogen was found on bronchoscopy and he died rapidly. In the lungs a massive necrosis was seen in which nonseptated hyphae identified as Mucor species were demonstrated.
Assuntos
Cladribina/efeitos adversos , Linfoma não Hodgkin/tratamento farmacológico , Mucormicose/etiologia , Pneumonia/microbiologia , Idoso , Cladribina/uso terapêutico , Evolução Fatal , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/uso terapêutico , Masculino , Pneumonia/patologiaRESUMO
We report the case of a 46-year old HIV-infected patient who suffered from severe recurrent diarrhoea for 18 months. In stool cultures cryptosporidiae were identified. The cryptosporidial enteritis was unresponsive to therapy. In the further course of cryptosporidial infection the patient developed HIV-associated cholangitis with increasing upper abdominal pain, progredient laboratory cholestasis and morphological changes indicating posthepatic cholestasis. Papillary stenosis with erosive papilitis caused by cryptosporidia was diagnosed. Sphincterotomy significantly improved the clinical status of the patient. Cholangitis with associated crytosporidial infection in a HIV-infected patient ist discussed and necessary diagnostic and differential therapeutic approaches are described.
Assuntos
Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Ampola Hepatopancreática , Colangite Esclerosante/diagnóstico , Colestase Extra-Hepática/diagnóstico , Criptosporidiose/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/patologia , Infecções Oportunistas Relacionadas com a AIDS/terapia , Ampola Hepatopancreática/patologia , Colangiopancreatografia Retrógrada Endoscópica , Colangite Esclerosante/patologia , Colangite Esclerosante/terapia , Colestase Extra-Hepática/patologia , Colestase Extra-Hepática/terapia , Coccidiostáticos/administração & dosagem , Terapia Combinada , Constrição Patológica/diagnóstico , Constrição Patológica/patologia , Constrição Patológica/terapia , Criptosporidiose/patologia , Criptosporidiose/terapia , Humanos , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Octreotida/administração & dosagem , Esfinterotomia EndoscópicaRESUMO
Trimetrexate (TMTX) is a new antifolate which avoids competition for cellular uptake with folinic acid (FA). A regimen of sequential TMTX, FA and 5-fluorouracil (5-FU) has shown efficacy in patients with colorectal cancer. Therefore, we treated 34 previously untreated patients with metastatic colorectal cancer with a weekly chemotherapy regimen consisting of 110 mg/m(2) of TMTX intravenously, then 24 h later 200 mg/m(2) of FA (i.v.) and 500 mg/m(2) of 5-FU (i. v.). Thereafter, 7 doses of oral FA (15 mg) were given at 6-hourly intervals. A treatment cycle consisted of 6 weeks of treatment, then 2 weeks of rest. All patients were treated as outpatients unless complications arose. Thirty-three patients were assessable for tumor response, and all 34 patients were assessable for toxicity. Twelve patients (36%; 95% confidence interval: 25-49%) achieved a partial response. The median duration of response was 8.5 months, and median survival was 14 months. The most common toxicity was diarrhea of grade 3/4, observed in 22% of treatment cycles; this decreased to 8% with early loperamide treatment. Hematologic toxicity was mild. The sequential administration of TMTX, FA and 5-FU is an active regimen in the first-line treatment of metastatic colorectal cancer and warrants further studies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias Colorretais/tratamento farmacológico , Adulto , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Medula Óssea/efeitos dos fármacos , Neoplasias Colorretais/patologia , Diarreia/induzido quimicamente , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Humanos , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Análise de Sobrevida , Resultado do Tratamento , Trimetrexato/administração & dosagem , Trimetrexato/efeitos adversosRESUMO
To reduce drug acquisition costs, the clinical and bacteriological efficacy of low-dose ceftazidime i.v. (1 g tid) was compared with cefotaxime i.v. (2 g tid). Both regimens were combined with netilmicin i.v. (2 mg/kg bodyweight tid), in an open, randomized, multicentre trial in febrile neutropenic patients. The addition of antibiotics for gram-positive coverage was part of the protocol; alteration in the antibiotics for gram-negative cover or premature discontinuation of the study antibiotics were judged as failure. One hundred and eighty six patients were randomized by nine German centres, the patients matched for age, underlying diseases and duration of neutropenia (median duration 14 days) in both treatment arms. Infections were documented microbiologically in 29% of the patients, clinically in 16% and suspected (fever of unknown origin) in 102/186 patients (55%). The 82 pathogens isolated were predominantly gram-positive bacteria. In an intent-to-treat analysis, the overall response rate without modification at the final evaluation was 58% in the ceftazidime group and 34% in the cefotaxime group (P < 0.01). The success rates with modification were 84% and 64%, respectively. The failure rate in a highly immunosuppressed subgroup of the patients (bone marrow transplant recipients) was higher for cefotaxime (53%) than for the ceftazidime arm (14%) (P < 0.001). Response rates were significantly higher in the ceftazidime group for patients with microbiologically documented and possible infections. No major bacterial superinfections occurred in the low-dose treatment arm. The tolerability was good for both regimens. Low-dose ceftazidime combined with netilmicin proved to be superior to recommended doses of cefotaxime/netilmicin in febrile neutropenic patients.
Assuntos
Infecções Bacterianas/tratamento farmacológico , Cefotaxima/uso terapêutico , Ceftazidima/uso terapêutico , Quimioterapia Combinada/uso terapêutico , Netilmicina/uso terapêutico , Neutropenia/tratamento farmacológico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Antibacterianos/uso terapêutico , Infecções Bacterianas/complicações , Cefotaxima/efeitos adversos , Ceftazidima/efeitos adversos , Cefalosporinas/efeitos adversos , Cefalosporinas/uso terapêutico , Resistência Microbiana a Medicamentos , Feminino , Febre/tratamento farmacológico , Febre/etiologia , Gentamicinas/efeitos adversos , Gentamicinas/uso terapêutico , Humanos , Masculino , Pessoa de Meia-Idade , Netilmicina/efeitos adversos , Neutropenia/complicações , Superinfecção , Resultado do TratamentoRESUMO
BACKGROUND: Patients with advanced multiple myeloma (stage III or progressive myeloma) received the CAD protocol every three weeks: cyclophosphamide 200 mg/m2 i.v./orally days 1-4, adriamycin 30 mg/m2 i.v. on day 1 and dexamethasone 40 mg p.o. days 1-4. PATIENTS AND METHODS: Forty-six patients with a median age of sixty years (range 34-84 years) were enrolled. According to Durie-Salmon 44 patients were in stage III, 2 in stage II; 6 patients had renal insufficiency (stage B). Twenty-three patients were pre-treated at least with melphalane/prednisone. RESULTS: Remission rates were as follows: complete remission 4%, partial remission 70%, minimal change 11%, no change 11%, progressive disease 4%. After an observation time of 14 months the median progression free interval for 33 patients not treated with subsequent high-dose chemotherapy with stem-cell support was more than 14 months. Overall, treatment was well tolerated. After 209 cycles given febrile neutropenia occurred in 11% of cycles including one fatal outcome. Neutropenia or thrombocytopenia grade 3-4 WHO was recorded in 18% and 6% of the cycles, respectively. CONCLUSIONS: This study shows that CAD is an effective regimen with an overall remission rate of 74%. The CAD protocol should be further evaluated in prospective trials.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Mieloma Múltiplo/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Ciclofosfamida/administração & dosagem , Dexametasona/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Doxorrubicina/administração & dosagem , Feminino , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Mieloma Múltiplo/patologia , Neutropenia/induzido quimicamente , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
Invasive fungal infections are a primary cause of morbidity and mortality in patients with hematological malignancies. Establishing a definite diagnosis of invasive fungal infection in febrile neutropenic patients is particularly challenging and time-consuming, but a delay of antifungal treatment leads to higher mortality. This situation has lead to the strategy of initiation "empirical" antifungal therapy prior to the detection of fungi. Meanwhile, improvements in diagnostic procedures are achieved, especially with imaging techniques and non-culture based methods which include antigen-based assays, metabolite detection and molecular detection of fungal DNA from body fluid samples using conserved or specific genome sequences. The AGIHO presents recommendations for the diagnosis of invasive fungal infections with risk-adapted screening concepts for the neutropenic and febrile episodes of patients with hemato-oncological disorders.