RESUMO
AIM: An open-label, phase I dose-escalation trial was performed in adult patients with various solid cancers to identify the maximum tolerated dose (MTD), to assess the safety, pharmacokinetic profile and anti-tumour activity of the new prodrug CAP7.1. The prodrug is converted to its active moiety etoposide via carboxylesterases in selective cells leading to a better tolerability and higher efficacy in therapeutic resistance cells and children with refractory neuroblastoma. PATIENTS AND METHODS: Eligible adult patients with advanced, refractory, solid malignancies received CAP7.1 as intravenous infusion on 5 consecutive days. Doses were escalated in four cohorts consisting of three to six patients, with a starting dose of 45 mg/m2/day. Treatment cycles were repeated in 21-day intervals in the absence of disease progression and prohibitive toxicity. The safety, pharmacokinetics and efficacy were evaluated, and the MTD and dose-limiting toxicity (DLT) were determined. RESULTS: Nineteen patients were assigned to four CAP7.1 dose cohorts (45, 90, 150 and 200 mg/m2/day). CAP7.1 was well tolerated. Haematotoxicity was observed at the two highest dose levels including three DLTs (two febrile neutropenia and one sepsis) only and were reversible with adequate therapy. No organ toxicity was observed. Non-haematological toxicities (mild-moderate) consist mainly of nausea, fatigue, vomiting, pyrexia and alopecia. One partial response and 11 stable diseases were observed as supporting signs of efficacy. CONCLUSION: MTD of CAP7.1 was reached at the dose of 200 mg/m2. A favourable safety profile and initial anti-tumour efficacy of CAP7.1 in therapeutic refractory tumours warrant further evaluation in clinical studies.
Assuntos
Etoposídeo/administração & dosagem , Neoplasias/tratamento farmacológico , Pró-Fármacos/administração & dosagem , Adulto , Idoso , Relação Dose-Resposta a Droga , Etoposídeo/efeitos adversos , Etoposídeo/farmacocinética , Feminino , Humanos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neoplasias/metabolismo , Pró-Fármacos/efeitos adversos , Pró-Fármacos/farmacocinéticaAssuntos
Biomarcadores Tumorais/genética , Predisposição Genética para Doença/genética , Testes Genéticos/métodos , Técnicas de Diagnóstico Molecular/métodos , Neoplasias/diagnóstico , Neoplasias/genética , Polimorfismo de Nucleotídeo Único/genética , Medicina Baseada em Evidências , Marcadores Genéticos/genética , HumanosRESUMO
BACKGROUND: Malignant ascites (MA) is associated with poor prognosis and limited palliative therapeutic options. Therefore, quality of life (QoL) assessment is of particular importance to demonstrate new treatment value. Following the demonstration of the superiority of catumaxomab and paracentesis over paracentesis on puncture-free survival, this analysis aimed at comparing deterioration in QoL between both the treatment options. PATIENTS AND METHODS: In a randomised, multicentre, phase II/III study of patients with MA due to epithelial cell adhesion molecule (EpCAM) positive cancer, the QoL was evaluated using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 items (EORTC QLQ-C30) questionnaire at screening, 1, 3 and 7 months after treatment and in the case of re-puncture on the day of paracentesis. Time to first deterioration in QoL was defined as a decrease in the QoL score of at least five points and compared between the catumaxomab (n=160) and control (n=85) groups using the log-rank test and Cox proportional hazards models adjusted for baseline score, country and primary tumour type. RESULTS: Deterioration in QoL scores appeared more rapidly in the control than in the catumaxomab group (median 19-26 days versus 47-49 days). The difference in time to deterioration in QoL between the groups was statistically significant for all scores (P<0.01). The hazard ratios ranged from 0.08 to 0.24 (P<0.01). CONCLUSIONS: Treatment with catumaxomab delayed deterioration in QoL in patients with MA. Compared with paracentesis alone, catumaxomab enabled patients to benefit from better QoL for a prolonged survival period.
Assuntos
Anticorpos Biespecíficos/uso terapêutico , Ascite/patologia , Ascite/terapia , Neoplasias/patologia , Neoplasias/terapia , Paracentese/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Neoplasias/metabolismo , Ascite/metabolismo , Moléculas de Adesão Celular/metabolismo , Terapia Combinada , Molécula de Adesão da Célula Epitelial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias/metabolismo , Neoplasias Ovarianas/metabolismo , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/terapia , Modelos de Riscos Proporcionais , Qualidade de Vida , Adulto JovemRESUMO
OBJECTIVE: Uveal melanoma primarily metastasizes hematogenously with metastases often confined to the liver. The aim of this study was to investigate the presence of circulating tumor cells (CTC) in patients with metastatic disease as a marker for systemic disease and to determine their prognostic relevance. METHODS: Blood samples from 68 patients were collected at the time of initial treatment of metastases. mRNA expression of tyrosinase and MelanA/MART1 as a surrogate marker for the presence of CTC was analyzed by real-time RT-PCR and compared with patient characteristics. RESULTS: CTC were detected in 63% of all patients and in 67% of the 48 patients with only liver metastases. Univariate and multivariate analyses revealed PCR results and serum lactate dehydrogenase as independent prognostic factors for progression-free (hazard ratios 2.2/3.5) and overall survival (hazard ratios 4.0/6.5). Combination of PCR and lactate dehydrogenase divided the patient cohort into 3 groups with distinct prognosis. CONCLUSION: CTC as evidence for systemic disease can be found in the majority of patients with metastatic uveal melanoma, including patients with visible disease confined to the liver. Detection of CTC-specific mRNA transcripts for tyrosinase and MelanA/MART1 by PCR is a poor prognostic factor for progression-free and overall survival. Characterization of CTC could improve the understanding of their biology.
Assuntos
Biomarcadores Tumorais/sangue , L-Lactato Desidrogenase/sangue , Neoplasias Hepáticas/secundário , Melanoma/sangue , Melanoma/secundário , Células Neoplásicas Circulantes/metabolismo , RNA Mensageiro/sangue , Neoplasias Uveais/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalo Livre de Doença , Feminino , Humanos , Estimativa de Kaplan-Meier , Avaliação de Estado de Karnofsky , Antígeno MART-1/genética , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/genética , Modelos de Riscos Proporcionais , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Taxa de Sobrevida , Neoplasias Uveais/patologiaRESUMO
BACKGROUND: This trial was designed to prove superiority of irinotecan over etoposide combined with carboplatin in extensive-disease small-cell lung cancer. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin area under the curve 5 mg x min/ml either in combination with irinotecan 50 mg/m2 on days 1, 8, and 15 (IP) or etoposide 140 mg/m2 on days 1-3 (EP). Primary end point was progression-free survival (PFS) at 6 months. Secondary end points were overall survival (OS), response rate, and toxicity. RESULTS: Of 226 patients, 216 were eligible. Median PFS was 6.0 months [95% confidence interval (CI) 5.0-7.0] in the IP arm and 6.0 months (95% CI 5.2-6.8) in EP arm (P = 0.07). Median survival was 10.0 months (95% CI 8.4-11.6) and 9.0 months (95% CI 7.6-10.4) in the IP and EP arm (P = 0.06), respectively. Hazard ratios for disease progression and OS were 1.29 (95% CI 0.96-1.73, P = 0.095) and 1.34 (95% CI 0.97-1.85, P = 0.072), respectively. No difference in response rates was observed. Grade 3 and 4 hematologic toxicity favored the IP arm, whereas diarrhea was significantly more frequent in the IP arm. CONCLUSION: This trial failed to show superiority of irinotecan over etoposide in combination with carboplatin.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Carboplatina/uso terapêutico , Etoposídeo/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/administração & dosagem , Camptotecina/uso terapêutico , Carboplatina/administração & dosagem , Intervalo Livre de Doença , Etoposídeo/administração & dosagem , Feminino , Alemanha , Humanos , Irinotecano , Neoplasias Pulmonares/patologia , Masculino , Pessoa de Meia-Idade , Carcinoma de Pequenas Células do Pulmão/patologiaRESUMO
BACKGROUND: It is unknown if discontinuation of targeted therapy (TT) and readministration in case of recurrence is feasible in patients with metastatic renal cell carcinoma (mRCC) in which complete response (CR) is achieved by TT alone or no evidence of disease (NED) with additional resection of residual metastases. PATIENTS AND METHODS: Patients in whom TT was discontinued after CR to TT alone or NED after additional metastasectomy were included in this retrospective analysis. Outcome criteria evaluated were time off TT, recurrence of metastases and response to re-exposure to TT. Univariate and multivariate analyses were carried out to identify variables potentially predictive of outcome. RESULTS: In 36 patients with CR or NED under TT with sunitinib (22), sorafenib (11), bevacizumab/interferon (2) and temsirolimus (1), TT was discontinued. Recurrence was observed in 24 patients (66.7%). Re-exposure to TT was effective in 86.9% of these cases. Twelve patients (33.3%) remained recurrence free at a median follow-up of 12 months (range 3-31). Median time off TT was 7 months (range 1-31). Factors that correlate with outcome could not be identified. CONCLUSIONS: In the majority of patients with mRCC and CR or NED, discontinuation of TT was followed by recurrence, but re-exposure to TT was effective.
Assuntos
Carcinoma de Células Renais/secundário , Carcinoma de Células Renais/terapia , Neoplasias Renais/patologia , Neoplasias Renais/terapia , Suspensão de Tratamento , Adulto , Idoso , Carcinoma de Células Renais/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Autologous hematopoietic SCT (auto-SCT) has been effective therapy for refractory disease, in both malignancies and severe autoimmune diseases. It seems feasible and safe for refractory celiac disease (RCD) type II, although long-term results have not been evaluated yet. With current therapies, progression into enteropathy-associated T-cell lymphoma (EATL) occurs in 60-80% patients, with a high mortality rate. Therefore, it is important to evaluate new treatment strategies. Between March 2004 and February 2010, 18 RCD II patients were evaluated for auto-SCT preceded by conditioning with fludarabine and melphalan, as a consequence of unresponsiveness to cladribine therapy. Adverse events, survival rate, EATL development and change in clinical, histological and immunological course were monitored. Thirteen patients were transplanted successfully and followed up for >2 years, 4-year survival rate was 66%. Only one patient died because of transplant-related complications. The majority of patients showed an impressive clinical improvement and five a complete histological remission. In five patients, auto-SCT could not be performed; they all died with a median survival of 5.5 months. EATL was observed in one transplanted patient, only after 4 years of follow-up. Auto-SCT after conditioning with high-dose chemotherapy in RCD II patients unresponsive to cladribine therapy is feasible and seems promising.
Assuntos
Doença Celíaca/terapia , Cladribina/uso terapêutico , Transplante de Células-Tronco Hematopoéticas/métodos , Terapia de Salvação/métodos , Adulto , Idoso , Antineoplásicos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Condicionamento Pré-Transplante , Transplante Autólogo , Resultado do TratamentoAssuntos
Neoplasias do Colo/sangue , Melanoma/sangue , Células Neoplásicas Circulantes , Idoso , Neoplasias do Colo/diagnóstico por imagem , Neoplasias do Colo/patologia , Feminino , Humanos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Metástase Neoplásica , Tomografia Computadorizada por Raios XRESUMO
The trifunctional bispecific monoclonal antibody catumaxomab has two binding specificities directed at epithelial cell adhesion molecule (EpCAM) and the T-cell antigen CD3. With its Fc-fragment, catumaxomab additionally binds accessory cells such as dendritic cells, macrophages and natural killer cells. The trifunctional approach thus leads to unrestricted but specific killing of epithelial tumor cells by major histocompatibility complex without the need for preactivation or external costimulation. The tumor-associated antigen EpCAM is strongly expressed in carcinomas of various origins including colon, rectum, ovarian, gastric, esophagus, lung, pancreas, breast and head and neck. Expression of EpCAM is often associated with an unfavorable prognosis in patients with breast cancer. Catumaxomab has been approved in Europe for the intraperitoneal treatment of malignant ascites in patients with EpCAM-positive epithelial tumors when standard therapy is not available or is no longer feasible. Basic preclinical and clinical findings with different routes of catumaxomab administration in various indications are summarized and discussed in this review.
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Anticorpos Biespecíficos/farmacologia , Antígenos de Neoplasias/efeitos dos fármacos , Antineoplásicos/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/imunologia , Animais , Anticorpos Biespecíficos/administração & dosagem , Anticorpos Biespecíficos/efeitos adversos , Anticorpos Biespecíficos/farmacocinética , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Antineoplásicos/farmacocinética , Vias de Administração de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Modelos ImunológicosRESUMO
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 on the case of a 64 year old male who received chemotherapy for a metastatic squamous cell carcinoma of the oropharynx. The chemotherapeutic regimen consisted of 5-fluorouracil (5-FU) and cisplatin. Six hours after completion of the first 24 h continuous infusion of 5-FU, the patient developed severe chest pain accompanied by vegetative symptoms and a pronounced ST-elevation of the precordial leads. Under the suspicion of an acute anterior myocardial infarction an immediate coronary angiogram was performed, demonstrating a total occlusion of the left anterior descending (LAD) coronary artery close to the left main stem. The other coronary arteries appeared smooth. After the intracoronary administration of nitroglycerine, the LAD reopened spontaneously without any residual stenosis, paralleled by complete relief of all symptoms. Therefore, 5-FU induced coronary spasm was diagnosed. After initial therapy with intravenous nitrate followed by oral calcium channel blocker, the patient remained free of symptoms and no rise in cardiac enzymes were noted. The chemotherapeutic regimen was changed to cisplatin plus docetaxel. No new attacks of chest pain occurred and the antivasospastic therapy could be stopped without further events.
Assuntos
Síndrome Coronariana Aguda/induzido quimicamente , Angina Pectoris/induzido quimicamente , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Carcinoma de Células Escamosas/secundário , Vasoespasmo Coronário/induzido quimicamente , Eletrocardiografia/efeitos dos fármacos , Fluoruracila/efeitos adversos , Neoplasias Primárias Desconhecidas/tratamento farmacológico , Neoplasias Orofaríngeas/secundário , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Idoso , Angina Pectoris/diagnóstico , Angina Pectoris/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/radioterapia , Cisplatino/administração & dosagem , Cisplatino/efeitos adversos , Terapia Combinada , Angiografia Coronária/efeitos dos fármacos , Vasoespasmo Coronário/diagnóstico , Diagnóstico Diferencial , Fluoruracila/administração & dosagem , Humanos , Infusões Intravenosas , Masculino , Neoplasias Primárias Desconhecidas/radioterapia , Nitroglicerina/administração & dosagem , Neoplasias Orofaríngeas/tratamento farmacológico , Neoplasias Orofaríngeas/radioterapia , Radioterapia Adjuvante , Vasodilatadores/administração & dosagemRESUMO
BACKGROUND: Metastatic uveal melanoma has a poor prognosis and limited therapeutic options. Proteoglycans are involved in tumor cell invasion and metastatic behavior. The mAbB5 stains a chondroitin sulphate proteoglycan (CSPG) on cutaneous melanoma cells. Here, we compare the B5-staining of CSPG in primaries and metastases of uveal melanoma. MATERIAL AND METHODS: Immunohistopathological staining was performed in 15 cutaneous and 39 uveal melanoma samples. A score for intracellular and surface staining was established. B5 staining was compared in primaries and metastases of uveal melanoma using Student's t-test. RESULTS: Eight of 11 (73%) uveal melanoma metastases were positive for B5-staining whereas only 5 of 28 (18%) primary uveal melanoma samples were B5-positive (P < 0.001). Nine of 15 cutaneous melanoma samples (60%) were B5-positive without significant difference between primary and metastatic lesions. Surface staining was found both on uveal melanoma metastases and cutaneous melanomas. CONCLUSIONS: CSPG was expressed significantly more often in metastases than in primaries of uveal melanoma. It potentially may be one factor associated with metastatic spread. Further studies are needed to determine its use as prognostic factor. The mAbB5 may also be a promising tool for immunotherapy due to its strong staining of CSPG on the surface of cutaneous and metastatic uveal melanoma cells.
Assuntos
Proteoglicanas de Sulfatos de Condroitina/metabolismo , Melanoma/metabolismo , Neoplasias Uveais/metabolismo , Humanos , Imuno-Histoquímica , Melanoma/patologia , Metástase Neoplásica , Neoplasias Uveais/patologiaRESUMO
BACKGROUND: Several trials demonstrated efficacy of the gemcitabine/treosulfan (GeT) combination in metastatic uveal melamoma. This randomized phase II trial compared the GeT combination versus treosulfan alone (T) in this rare disease. PATIENTS AND METHODS: Chemotherapy-naive patients with proven metastatic uveal melanoma were randomly assigned to receive 1000 mg/m(2) of gemcitabine plus 3500 mg/m(2) of treosulfan (GeT) or 3500 mg/m(2) of T. Chemotherapy was administered on days 1 and 8 in both arms, cycles were repeated on day 29. Primary end point was rate of responses and disease stabilizations. RESULTS: Forty-eight patients were randomized. Seven confirmed stable diseases (SDs) and one partial remission (PR) were observed in 24 patients treated with the GeT regimen, whereas no PR and only three SDs were observed in the T arm (P = 0.08). Median progression-free survival (PFS) was 3 months (95% CI 1.1-4.9) and 2 months (95% CI 1.7-2.3) in the GeT and T arm (P = 0.008, log-rank). Six and 12 months PFS was 34.8% and 17.9% and 16.7% and 0% always favoring the GeT arm. CONCLUSIONS: This first randomized trial in metastatic uveal melanoma showed a superior PFS and a trend for a higher response/stabilization rate of the GeT combination over T.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Melanoma/tratamento farmacológico , Neoplasias Uveais/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Bussulfano/administração & dosagem , Bussulfano/análogos & derivados , Desoxicitidina/administração & dosagem , Desoxicitidina/análogos & derivados , Feminino , Humanos , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Análise de Sobrevida , Neoplasias Uveais/patologia , GencitabinaRESUMO
BACKGROUND: Superiority of irinotecan/cisplatin over etoposide/cisplatin was suggested in small-cell lung cancer (SCLC). This trial investigated irinotecan/carboplatin (IP) versus etoposide/carboplatin (EP). PATIENTS AND METHODS: The interim analysis at the phase II/phase III transition point of the multicenter trial is reported. Extensive disease SCLC patients were randomized to receive carboplatin AUC 5 mg x min/ml either in combination with 50 mg/m2 of irinotecan on days 1, 8 and 15 (IP) or with etoposide 140 mg/m2 days 1-3 (EP). The primary end point was response rate and the secondary end points were toxicity and progression-free survival. RESULTS: Seventy patients were randomized. Significant differences in grade 3 and 4 thrombopenia (17% IP versus 48% EP, P = 0.01) and neutropenia (26% IP versus 51% PE, P < 0.01) were found. Grade 3 and 4 diarrhea was more frequent with IP (18%) than with EP (6%) (P = 0.133). Response rates were 67% and 59% (P = 0.24) in the IP versus EP arm, respectively. Median progression-free survival (PFS) was 9 months (95% CI 7.1-10.9) in the IP arm and 6 months (95% CI 4.1-7.9) in the EP arm (P = 0.03). CONCLUSIONS: IP is active, less toxic and appears to improve PFS. Based on the phase II results the trial has been extended to phase III to assess the impact on overall survival.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma de Células Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Camptotecina/administração & dosagem , Camptotecina/análogos & derivados , Carboplatina/administração & dosagem , Etoposídeo/administração & dosagem , Feminino , Humanos , Irinotecano , Masculino , Pessoa de Meia-IdadeRESUMO
BACKGROUND: The dose of high-dose methotrexate (HDMTX) in elderly patients often has to be reduced, resulting in a loss of treatment efficacy. We evaluated HDMTX-related toxicity with special regard to age distribution in patients with primary central nervous system lymphoma (PCNSL) in a phase IV multicenter trial. PATIENTS AND METHODS: One hundred and fifty-four patients (median age 61 years; 89 patients >60 years old, 21 patients >70 years old) received 619 HDMTX cycles. Toxicity was evaluated prospectively using the WHO classification. Unless a reduced dose was required after calculating a decreased glomerular filtration rate (GFR), the patients received 4 g/m(2) HDMTX followed by leucovorin rescue. RESULTS: Toxicity was generally mild with toxicities of WHO grade > or =3 usually <10%. The differences in the incidence and severity of toxicity were not statistically significant between patients >60 years and < or =60 years old. The same was true for therapy termination owing to MTX toxicity and for delayed serum MTX clearance. Dose reduction significantly differed between patients < or =60 years and those >60 years old (18% versus 44%; P = 0.001). CONCLUSIONS: HDMTX is a safe treatment for PCNSL patients regardless of age, with adherence to dose reduction determined by calculating the GFR before each treatment cycle.
Assuntos
Antimetabólitos Antineoplásicos/efeitos adversos , Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias do Sistema Nervoso Central/tratamento farmacológico , Linfoma/tratamento farmacológico , Metotrexato/efeitos adversos , Metotrexato/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/farmacocinética , Neoplasias do Sistema Nervoso Central/patologia , Feminino , Taxa de Filtração Glomerular , Humanos , Linfoma/patologia , Masculino , Metotrexato/administração & dosagem , Metotrexato/farmacocinética , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: Superiority of irinotecan (CPT-11) plus cisplatin over etoposide plus cisplatin in small cell lung cancer (SCLC) has recently been demonstrated. This study determines dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of escalating doses of carboplatin to a fixed dose of irinotecan in Caucasians with small cell lung cancer. PATIENTS AND METHODS: Patients with extensive small cell lung cancer received 50 mg/m(2) irinotecan on day 1, 8, and 15. Dose escalation of carboplatin on day 1 started in dose level 1 at an AUC of 5 mg x min/ml and was escalated to AUC 6 in level 2. Cycles were repeated on day 29. Dose escalation was evaluated after 3 consecutive patients. If no grade IV neutropenia lasting for > or =7 days or thrombopenia or non-hematologic toxicity > or = grade III occurred, treatment was continued in the next dose level. RESULTS: 16 patients were treated. DLT was reached in dose level 2 with 2 grade IV neutropenias and 1 grade IV thrombopenia and diarrhea. Toxicity was further investigated at dose level 1 in a total of 10 patients, which revealed 2 grade III neutropenias and 1 grade III diarrhea. Of 15 evaluable patients, 10 had a partial response, 3 had disease stabilization and 2 progressed. CONCLUSION: Dose level 1 was found to be MTD, this dose is currently compared to the combination of etoposide plus carboplatin within a randomised phase II/III trial.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Camptotecina/análogos & derivados , Camptotecina/administração & dosagem , Camptotecina/efeitos adversos , Carboplatina/administração & dosagem , Carboplatina/efeitos adversos , Carcinoma de Células Pequenas/tratamento farmacológico , Idoso , Carcinoma de Células Pequenas/diagnóstico por imagem , Relação Dose-Resposta a Droga , Feminino , Humanos , Irinotecano , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/tratamento farmacológico , Dose Máxima Tolerável , Pessoa de Meia-Idade , Neutropenia/induzido quimicamente , Radiografia , Trombocitopenia/induzido quimicamente , Resultado do TratamentoRESUMO
BACKGROUND: Fatigue is a frequent and severe problem after treatment of patients with hematological malignancies. This symptom has been associated with anemia, reduced physical performance, mood, endocrine disorders and impaired nutritional status. Recently, it has been suggested that fatigue can be related to a persistent activation of the immune system with increased production of proinflammatory cytokines. However, there is no conclusive evidence regarding the role of the immune system in the origin of fatigue in cancer patients. PATIENTS AND METHODS: We evaluated the correlation of fatigue with thyroid function, markers of immune activity [interleukin (IL)-1alpha, IL-1 soluble receptor, IL-6, C-reactive protein and neopterin], liver and kidney function, mood and physical ability in 71 patients with hematological malignancies. All patients had been free of relapse and not received treatment (chemotherapy, radiotherapy or immune modulators) for at least 3 months. RESULTS: Fatigue was related to depression (r=0.84; P<0.0001) and reduced performance status (r=-0.61; P<0.0001). However, there was no correlation between fatigue and thyroid, liver and kidney function, anemia, albumin concentration or markers of immune activity (all r-values <0.20; P>0.05). CONCLUSIONS: We conclude that fatigue in relapse-free patients with hematological malignancies is associated with depressive mood and reduced physical performance, but not with impairment of thyroid function, anemia or persistent activation of the immune system.
Assuntos
Depressão/etiologia , Fadiga/etiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/tratamento farmacológico , Glândula Tireoide/fisiologia , Adulto , Idoso , Citocinas/análise , Intervalo Livre de Doença , Feminino , Nível de Saúde , Neoplasias Hematológicas/psicologia , Humanos , Sistema Imunitário/fisiologia , Rim/fisiologia , Fígado/fisiologia , Masculino , Pessoa de Meia-Idade , Aptidão FísicaAssuntos
Antibacterianos/farmacologia , Antineoplásicos Fitogênicos/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Camptotecina/análogos & derivados , Camptotecina/efeitos adversos , Diarreia/induzido quimicamente , Diarreia/prevenção & controle , Neomicina/farmacologia , Administração Oral , Antibacterianos/uso terapêutico , Antidiarreicos/uso terapêutico , Antineoplásicos Fitogênicos/uso terapêutico , Camptotecina/uso terapêutico , Fluoruracila/administração & dosagem , Humanos , Irinotecano , Leucovorina/administração & dosagem , Loperamida/uso terapêutico , Neomicina/uso terapêuticoRESUMO
This study analyses the frequency and therapy of brain metastases in 94 stage IV melanoma patients after treatment with high-dose interleukin-2 (IL-2) and interferon-alpha (IFN-alpha) within three subsequent trials between 1990 and 1995. Central nervous system (CNS) metastases occurred in 28 patients (30%) during the potential follow-up period of 6 years. Time to occurrence of brain metastases varied between 1 and 53 months, with a median of 10 months. Of 28 patients, 19 had < 5 metastases, which were treated with stereotactic radiosurgery (SR) in 9 patients. In 2 patients, SR was followed by resection. 9 patients had multiple metastases, of which 4 received whole brain irradiation (WBI). Median survival after the detection of CNS metastases was 6 months (95% Confidence Interval (CI) 1-11 months). SR plus resection was associated with a prolonged survival of 34 and 35 months in 2 patients, 1 patient survived for 41 months after WBI, demonstrating the efficacy of these therapeutic strategies.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Encefálicas/secundário , Melanoma/tratamento farmacológico , Melanoma/secundário , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Encefálicas/terapia , Seguimentos , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Interleucina-2/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Proteínas Recombinantes , Neoplasias Cutâneas/patologia , Análise de SobrevidaRESUMO
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