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1.
Medicina (Kaunas) ; 59(12)2023 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-38138217

RESUMO

Medical imaging is the mainstay of clinical diagnosis and management. Optical coherence tomography (OCT) is a non-invasive imaging technology that has revolutionized the field of ophthalmology. Since its introduction, OCT has undergone significant improvements in image quality, speed, and resolution, making it an essential diagnostic tool for various ocular pathologies. OCT has not only improved the diagnosis and management of ocular diseases but has also found applications in other fields of medicine. In this manuscript, we provide a brief overview of the history of OCT, its current uses and diagnostic capabilities to assess the posterior segment of the eye, and the evolution of this technology from time-domain (TD) to spectral-domain (SD) and swept-source (SS). This brief review will also discuss the limitations, advantages, disadvantages, and future perspectives of this technology in the field of ophthalmology.


Assuntos
Oftalmologia , Tomografia de Coerência Óptica , Humanos , Tomografia de Coerência Óptica/métodos
2.
Life (Basel) ; 12(8)2022 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-36013328

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have revolutionized the therapeutic horizons of various cancers. However, immune-related adverse events have been reported, including interstitial lung diseases. Our aim was to describe the clinical and radiological features and survival of a multicentre cohort of patients who developed ICI-related lung toxicity. METHODS: Six Italian centres were involved in the study. Patients who were treated with anti-PD-1/PD-L1 and CTLA-4 mAbs and developed ICI-related lung toxicity were recruited retrospectively to study clinical, radiological, immunological and survival data. RESULTS: A total of 41 patients (25 males, 66.8 ± 9.9 years) were enrolled. Lung toxicity occurred after 204.3 ± 208.3 days of therapy, with ground glass opacities being the most common HRCT pattern (23 cases). Male sex, lung cancer and acute respiratory failure were associated with a shorter latency of toxicity (p = 0.0030, p = 0.0245 and p = 0.0390, respectively). Patients who required high-flow oxygen therapy showed significantly worse survival (p = 0.0028). CONCLUSIONS: Our cohort showed heterogeneous clinical and radiological aspects of ICI-related lung toxicity, with a latency not limited to the first year of treatment. Severity was mainly mild to moderate, although life-threatening events did occur. Our data indicate that strict long-term follow-up is needed to enable early diagnosis and appropriate management.

3.
Biology (Basel) ; 10(3)2021 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-33805806

RESUMO

Ribonuclease (RNase) H2 is a key enzyme for the removal of RNA found in DNA-RNA hybrids, playing a fundamental role in biological processes such as DNA replication, telomere maintenance, and DNA damage repair. RNase H2 is a trimer composed of three subunits, RNASEH2A being the catalytic subunit. RNASEH2A expression levels have been shown to be upregulated in transformed and cancer cells. In this study, we used a bioinformatics approach to identify RNASEH2A co-expressed genes in different human tissues to underscore biological processes associated with RNASEH2A expression. Our analysis shows functional networks for RNASEH2A involvement such as DNA replication and DNA damage response and a novel putative functional network of cell cycle regulation. Further bioinformatics investigation showed increased gene expression in different types of actively cycling cells and tissues, particularly in several cancers, supporting a biological role for RNASEH2A but not for the other two subunits of RNase H2 in cell proliferation. Mass spectrometry analysis of RNASEH2A-bound proteins identified players functioning in cell cycle regulation. Additional bioinformatic analysis showed that RNASEH2A correlates with cancer progression and cell cycle related genes in Cancer Cell Line Encyclopedia (CCLE) and The Cancer Genome Atlas (TCGA) Pan Cancer datasets and supported our mass spectrometry findings.

4.
Surg Oncol ; 37: 101523, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33545658

RESUMO

BACKGROUND: Few prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31). MATERIALS AND METHODS: Between 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC. RESULTS: A complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26-45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29-76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19-27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors. CONCLUSIONS: A novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.


Assuntos
Quimioterapia Adjuvante/métodos , Procedimentos Cirúrgicos de Citorredução/métodos , Quimioterapia Intraperitoneal Hipertérmica/métodos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/cirurgia , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Feminino , Humanos , Quimioterapia Intraperitoneal Hipertérmica/efeitos adversos , Itália , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , Estadiamento de Neoplasias , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/patologia , Taxa de Sobrevida
5.
Cancer Med ; 9(6): 2052-2061, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31991072

RESUMO

BACKGROUND: Although the efficacy of molecularly target agents in vitro, their use in routine setting is limited mainly to the use of anti-HER2 and antiEGFR agents in vivo. Moreover, core biopsy of a single cancer site may not be representative of the whole expanding clones and cancer molecular profile at relapse may differ with respect to the primary tumor. METHODS: We assessed the status of a large panel of cancer driver genes by cell-free DNA (cfDNA) analysis in a cohort of 68 patients with 13 different solid tumors at disease progression. Whenever possible, a second cfDNA analysis was performed after a mean of 2.5 months, in order to confirm the identified clone(s) and to check the correlation with clinical evolution. RESULTS: The approach was able to identify clones plausibly involved in the disease progression mechanism in about 65% of cases. A mean of 1.4 mutated genes (range 1-3) for each tumor was found. Point mutations in TP53, PIK3CA, and KRAS and copy number variations in FGFR3 were the gene alterations more commonly observed, with a rate of 48%, 20%, 16%, and 20%, respectively. Two-points-Next-Generation Sequencing (NGS) analysis demonstrated statistically significant correlation between allele frequency variation and clinical outcome (P = .026). CONCLUSIONS: Irrespective of the primary tumor mutational burden, few mutated genes are present at disease progression. Clinical outcome is consistent with variation of allele frequency of specific clones indicating that cfDNA two-point-NGS analysis of cancer driver genes could be an efficacy tool for precision oncology.


Assuntos
Biomarcadores Tumorais/genética , DNA Tumoral Circulante/genética , Análise Mutacional de DNA , Sequenciamento de Nucleotídeos em Larga Escala , Neoplasias/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Criança , Pré-Escolar , DNA Tumoral Circulante/sangue , Evolução Clonal , Variações do Número de Cópias de DNA , Progressão da Doença , Estudos de Viabilidade , Feminino , Seguimentos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/sangue , Neoplasias/genética , Neoplasias/terapia , Mutação Puntual , Medicina de Precisão/métodos , Estudos Prospectivos , Adulto Jovem
6.
Cancer Cell Int ; 19: 274, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31673247

RESUMO

BACKGROUND: Daily experience tells us that breast cancer can be controlled using standard protocols up to the advent of a relapse. Now new frontiers in precision medicine like liquid biopsy of cell free DNA (cfDNA) give us the possibility to understand cancer evolution and pick up the key mutation on specific cancer driver gene. However, tight schedule of standardized protocol may impair the use of personalized experimental drugs in a timely therapeutic window. MAIN BODY: Here, using a combination of deep next generation sequencing and cfDNA liquid biopsy, we demonstrated that it is possible to monitor cancer relapse over time. We showed for the first time the exact correspondence from the increasing clonal expansion and clinical worsening of metastatic breast cancer. CONCLUSION: Thanks to liquid biopsy may be possible to introduce new experimental drugs in the correct therapeutic window which would lead in the near future to an effective treatment which otherwise remains challenging.

7.
Int J Hyperthermia ; 32(3): 298-310, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26984715

RESUMO

Hyperthermic intraperitoneal chemotherapy (HIPEC), a strategy combining maximal cytoreductive surgery and maximal regional chemotherapy, has been applied to treat ovarian cancer resulting in long-term survival rates in selected patients. However, the status of HIPEC in ovarian cancer remains an experimental procedure, given the many variables among the data and trials reviewed, to enable us to derive strong conclusions about its role from this overview. In this review we discuss treatment with HIPEC in patients with ovarian cancer and future prospective of its use in clinical setting. HIPEC is an effective tool in the treatment of selected patients with peritoneal carcinomatosis from ovarian cancer. Unfortunately, due to the lack of randomised trials, the evidence of HIPEC is very limited. Future randomised studies are awaited to define the role and clinical impact of HIPEC in ovarian cancer.


Assuntos
Quimioterapia do Câncer por Perfusão Regional , Procedimentos Cirúrgicos de Citorredução , Hipertermia Induzida , Neoplasias Ovarianas/terapia , Animais , Terapia Combinada , Feminino , Humanos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/epidemiologia , Neoplasias Ovarianas/cirurgia , Prognóstico , Resultado do Tratamento
8.
Int J Surg Pathol ; 23(4): 317-21, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25722316

RESUMO

Gastrointestinal stromal tumor (GIST) metastases are found most commonly in the liver, on average 16 to 38 months after resection of the primary tumor, even if some delayed hepatic metastases from GISTs have been described. We report a case of a man with a giant liver mass at computed tomography scan. In September 1984, the patient had undergone resection of a duodenal tumor, diagnosed as schwannoma. A liver biopsy revealed a neoplasm composed of epithelioid and spindled cells, immunohistochemically positive to c-kit and Dog-1. Reexamining the duodenal tumor resected in 1984, it was reclassified as GIST. Sequencing revealed the same mutation of the c-kit gene in both duodenal and hepatic lesions. To the best of our knowledge, this case represents the longest disease-free interval between a primary GIST and its metastasis. A brief review of the literature and an analysis of the potential prognostic role of particular c-kit mutations are also provided.


Assuntos
Neoplasias Duodenais/patologia , Tumores do Estroma Gastrointestinal/secundário , Neoplasias Hepáticas/secundário , Adulto , Idade de Início , Idoso , Biomarcadores Tumorais/análise , Análise Mutacional de DNA , Neoplasias Duodenais/genética , Tumores do Estroma Gastrointestinal/genética , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/genética , Masculino , Metástase Neoplásica/genética , Metástase Neoplásica/patologia , Proteínas Proto-Oncogênicas c-kit/genética
9.
Case Rep Oncol ; 6(3): 538-43, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24348390

RESUMO

Glioblastoma multiforme (GBM) is the most lethal subtype of glioma, classified as a WHO grade 4 infiltrative glioma. The etiology of GBM remains unknown and risk factors can be identified only in a small minority. We report the synchronous occurrence of GBM in an otherwise unrelated married couple, i.e. a husband and his wife, who developed GBM within an interval of 1 month. No specific causative environmental factors were identified for both patients, and the genetic screens were negative for hereditary syndromes. Family history was negative for tumors, and no other incidence of cancer in either siblings, parents or other children was reported. An analysis of the couple's exposure to nonionizing electromagnetic fields and ionizing radiations revealed values within the normal ranges usually found in homes. Overall, conjugal tumors are rarely reported. However, the case reported herein raises important questions about possible etiologic factors.

10.
J Biol Chem ; 288(48): 34484-93, 2013 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-24129572

RESUMO

Differentiated retinal pigmented epithelial (RPE) cells have been obtained from human induced pluripotent stem (hiPS) cells. However, the visual (retinoid) cycle in hiPS-RPE cells has not been adequately examined. Here we determined the expression of functional visual cycle enzymes in hiPS-RPE cells compared with that of isolated wild-type mouse primary RPE (mpRPE) cells in vitro and in vivo. hiPS-RPE cells appeared morphologically similar to mpRPE cells. Notably, expression of certain visual cycle proteins was maintained during cell culture of hiPS-RPE cells, whereas expression of these same molecules rapidly decreased in mpRPE cells. Production of the visual chromophore, 11-cis-retinal, and retinosome formation also were documented in hiPS-RPE cells in vitro. When mpRPE cells with luciferase activity were transplanted into the subretinal space of mice, bioluminance intensity was preserved for >3 months. Additionally, transplantation of mpRPE into blind Lrat(-/-) and Rpe65(-/-) mice resulted in the recovery of visual function, including increased electrographic signaling and endogenous 11-cis-retinal production. Finally, when hiPS-RPE cells were transplanted into the subretinal space of Lrat(-/-) and Rpe65(-/-) mice, their vision improved as well. Moreover, histological analyses of these eyes displayed replacement of dysfunctional RPE cells by hiPS-RPE cells. Together, our results show that hiPS-RPE cells can exhibit a functional visual cycle in vitro and in vivo. These cells could provide potential treatment options for certain blinding retinal degenerative diseases.


Assuntos
Células-Tronco Pluripotentes Induzidas/transplante , Degeneração Retiniana/genética , Degeneração Retiniana/terapia , Epitélio Pigmentado da Retina/transplante , cis-trans-Isomerases/genética , Animais , Diferenciação Celular , Células Cultivadas , Regulação Enzimológica da Expressão Gênica , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Células-Tronco Pluripotentes Induzidas/enzimologia , Camundongos , Degeneração Retiniana/patologia , Epitélio Pigmentado da Retina/enzimologia , Retinaldeído/biossíntese , Retinaldeído/genética , Visão Ocular/genética , Visão Ocular/fisiologia , cis-trans-Isomerases/deficiência
11.
J Surg Oncol ; 102(6): 663-70, 2010 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-20721959

RESUMO

OBJECTIVES: To analyze the outcomes of cytoreductive surgery and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. METHODS: Fifty-three patients with peritoneal carcinomatosis from primary (45 cases) and recurrent (8 cases) ovarian cancer were previously treated by systemic chemotherapy with platinum and taxanes and then submitted to surgical cytoreduction and HIPEC (cisplatin and mitomycin-C) with a closed abdomen technique. The median follow-up period was 27 months (range: 3-107). RESULTS: At the end of operation a complete cytoreduction (CCR-0) was obtained in 37 patients (70%). Major morbidity occurred in 12 patients (23%); reoperation was necessary in 2 patients (4%), and no postoperative mortality was observed. Overall 5-year survival probability was 55%; it was 71% in CCR-0, 44% in CCR-1, and none in patients with CCR-2 or CCR-3 residual tumor (log-rank test: P = 0.017). The cumulative risk of recurrence in 37 CCR-0 cases was 54% at 5 years from operation. CONCLUSIONS: The results of our study indicate the feasibility and the potential benefit of a protocol including systemic chemotherapy, surgical cytoreduction and HIPEC in patients with peritoneal carcinomatosis from ovarian cancer. A phase III trial to compare this approach with conventional treatment is needed.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Carcinoma/tratamento farmacológico , Carcinoma/secundário , Neoplasias Ovarianas/patologia , Neoplasias Peritoneais/tratamento farmacológico , Neoplasias Peritoneais/secundário , Adulto , Idoso , Carcinoma/cirurgia , Quimioterapia do Câncer por Perfusão Regional , Terapia Combinada , Feminino , Humanos , Hipertermia Induzida , Injeções Intraperitoneais , Pessoa de Meia-Idade , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Neoplasias Peritoneais/cirurgia , Recidiva , Resultado do Tratamento
12.
Tumori ; 95(3): 329-37, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19688972

RESUMO

AIMS AND BACKGROUND: No available scientific report deals with high-dose (> or = 70 Gy) radiotherapy plus temozolomide chemotherapy (TMZ CHT) in high-grade gliomas. The survival results of a protocol-driven, postoperative treatment schedule are reported here to contribute to the discussion on this issue. METHODS AND STUDY DESIGN: Uniform criteria were prospectively adopted for case selection during the period 1993-2006 in the management of 123 patients, and we progressively introduced three-dimensional conformal radiotherapy (3D-CRT, 60 Gy), TMZ CHT and a high-dose (70 Gy) stereotactic boost (HDSRT) in the treatment schedule. Palliative radiotherapy was delivered by whole brain irradiation (WBI, 50 Gy) for bulky tumors, whereas radical irradiation was performed with 3D-CRT throughout the study period. Two periods of accrual are considered: 36 patients were treated before 31 December 1999 (29.25%) and 87 (70.75%) after 1 January 2000. This subdivision was due to the implementation of HDSRT hardware and TMZ CHT from January 2000. RESULTS: The median overall survival was 13 months and the 1-, 2- and 3-year survival rates were 53%, 19.5% and 11.6%, respectively. The differences in survival related to the treatment variables were highly significant, both in univariate and multivariate analysis. The median survival and 1-, 2- and 3-year survival rates in the palliative WBI group were 9.75 months and 37%, 2%, and 0%, respectively; in the 3D-CRT group 17.25 months and 64%, 34%, and 15%, respectively; in the TMZ CHT concomitant with radiotherapy group 20 months and 61%, 39%, and 21%, respectively; in the TMZ CHT concomitant with and sequential to radiotherapy group 25.75 months and 84%, 54%, and 26%, respectively, and in the HDSRT group 22 months and 72%, 48%, and 37%, respectively. No symptomatic radiation necrosis occurred in any of the groups. CONCLUSIONS: The results reported here are generally better than those reported in the literature. The selection of patients on the basis of favorable prognostic factors and suitability to the currently available, aggressive postoperative treatment resources can be the mainstay for improving therapeutic results. In particular, the new treatment option reported here (HDSRT in association with TMZ CHT) proved to be safe and effective in obtaining a relatively favorable outcome.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/radioterapia , Irradiação Craniana/métodos , Dacarbazina/análogos & derivados , Glioma/tratamento farmacológico , Glioma/radioterapia , Radioterapia Conformacional , Adulto , Idoso , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Quimioterapia Adjuvante , Protocolos Clínicos , Dacarbazina/uso terapêutico , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Período Pós-Operatório , Prognóstico , Modelos de Riscos Proporcionais , Radioterapia Adjuvante/métodos , Radioterapia Conformacional/métodos , Técnicas Estereotáxicas , Análise de Sobrevida , Temozolomida , Resultado do Tratamento
13.
Autophagy ; 5(7): 930-6, 2009 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-19556884

RESUMO

High-grade gliomas (HGG) have a poor outcome, however, prognostic subgroups of patients may be individuated by some clinico-biological parameters. It was recently demonstrated that the main response of HGG to therapy is autophagic death. Autophagy is involved in tumor suppression, and is defective in HGG, in which we previously found an underexpression of beclin 1 autophagic gene protein product. Underexpression of Beclin 1 protein has been correlated to poor patient outcome in other tumor types. In this paper, the prognostic role of Beclin 1 expression in HGG patients was investigated. We first evaluated the tumor cell cytoplasmic expression of Beclin 1 protein (BPCE), in a sample of 76 HGG by immunohistochemistry, and compared it with cell proliferation and apoptosis. We found high BPCE score positively correlated with apoptosis, and negatively with cell proliferation (p < 0.05). We then correlated BPCE score with survival and other prognostic parameters (histological grading, MGMT gene methylation status, age, patient performance status according to the Karnofski classification (KPS), extent of surgery, radiation therapy (RT) modality, temozolomide chemotherapy (TMZ CHT), and optimal/suboptimal post-surgical treatment). Forty-seven (61.8%) and twenty-nine (38.2%) patients showed high and low BPCE scores, respectively. BPCE showed statistically significant correlations with survival both at the univariate (p = 0.03) and multivariate analysis (p = 0.037). High BPCE was also positively correlated with high KPS values (p = 0.023), and with the accomplishment of an optimal postoperative therapy (p = 0.037). Furthermore, among patients showing a MGMT methylated gene, survival was significantly higher in cases with a higher BPCE score. BPCE score might be added to pathological evaluation of HGG for prognostic purposes.


Assuntos
Proteínas Reguladoras de Apoptose/metabolismo , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Glioma/metabolismo , Glioma/patologia , Proteínas de Membrana/metabolismo , Antineoplásicos Alquilantes/uso terapêutico , Proteínas Reguladoras de Apoptose/genética , Autofagia/fisiologia , Proteína Beclina-1 , Biomarcadores Tumorais/metabolismo , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/terapia , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Glioma/diagnóstico , Glioma/terapia , Humanos , Marcação In Situ das Extremidades Cortadas , Proteínas de Membrana/genética , Pessoa de Meia-Idade , Prognóstico , Análise de Sobrevida , Temozolomida , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
14.
Cancer Chemother Pharmacol ; 61(1): 105-11, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-17429632

RESUMO

PURPOSE: The dose limiting toxicity of oxaliplatin (l-HOP) is neurotoxicity, which is characterized by an acute neuropathy and a clinically distinct chronic neuropathy. This randomized study evaluated if prolonged l-HOP infusion over the conventional l-HOP schedule was useful in reducing acute and possibly chronic l-HOP induced neurotoxicity in colon and gastric cancer patients receiving l-HOP-based regimen as adjuvant chemotherapy. METHODS: Sixty-four patients were randomly assigned to group A (26 colon and 6 gastric cancer) and to group B (23 colon and 9 gastric cancer). Chemotherapy in both groups consisted of l-HOP 85 mg/m(2) i.v. only on day 1, with leucovorin 100 mg/m(2) i.v. as a 2-h infusion followed by bolus 5-fluorouracil (5-FU) 400 mg/m(2)/day and a 22-h infusion of 5-FU 600 mg/m(2)/day, repeated for two consecutive days every 2 weeks for a maximum of 12 cycles. Patients in group A received l-HOP as a continuous 6-h i.v. infusion, and patients in group B received l-HOP as the conventional 2-h i.v. infusion. RESULTS: The percentage of patients presenting with grade >/=2 neurotoxicity was statistically lower in group A than in group B (28.1% vs. 59.3%: P = 0.02). There was a statistically lower percentage of cycles with grade >/=2 neurotoxicity in group A (6.1%) than in group B (18.5%) (P < 0.001). CONCLUSIONS: This study suggests that l-HOP as a continuous 6-h infusion is useful in preventing and reducing acute l-HOP induced neurotoxicity in patients with colon and gastric cancer receiving FOLFOX-4 regimen as adjuvant treatment.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias do Colo/tratamento farmacológico , Síndromes Neurotóxicas/etiologia , Neoplasias Gástricas/tratamento farmacológico , Doença Aguda , Adulto , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Seguimentos , Humanos , Infusões Intravenosas , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Dose Máxima Tolerável , Pessoa de Meia-Idade , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos
15.
Anticancer Drugs ; 19(1): 91-6, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18043134

RESUMO

The aim of this study was to investigate the safety profile of continuous oral capecitabine at fixed dose in patients older than 75 years, having metastatic colorectal and gastric cancer. Capecitabine was administered at a fixed dose of 2000 mg daily without interruptions. Thirty-four patients were considered evaluable for toxicity and efficacy. The median age was 81 years (range 76-85). The median duration of treatment was 113 days (range 24-238 days). No grade 4 toxicity was observed. One patient had grade 3 nausea and vomiting, and one had grade 3 diarrhea. Partial responses were observed in six patients with colorectal cancer, and in one patient with gastric cancer. This study suggests that continuous oral capecitabine at a fixed daily dose of 2000 mg is well tolerated, and that it allows for the simplification and ease of dosing in elderly patients with metastatic colorectal and gastric cancer.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias Gástricas/tratamento farmacológico , Idoso , Idoso de 80 Anos ou mais , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Masculino , Metástase Neoplásica , Neoplasias Gástricas/patologia
16.
Anticancer Drugs ; 18(7): 817-20, 2007 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-17581304

RESUMO

The aim of this study was to evaluate the activity and toxicity of capecitabine as third-line treatment in patients with advanced renal cell carcinoma for whom immunotherapy had failed. Twenty-one patients with metastatic clear renal cell carcinoma were enrolled. Capecitabine was administered orally twice daily at a dosage of 2500 mg/m(2) for 14 days, followed by 7 days of rest. The median number of administered cycles was five (1-13). One patient (4.8%) achieved a remission after eight treatment cycles. Stable disease was observed in nine patients (42.8%), whereas 11 progressed (52.4%). The estimated median time to progression was 3.6 months (confidence interval: 1.4 to 5.2). The estimated median overall survival was 7.2 months (confidence interval: 4.6 to 8.8). The regimen was well tolerated and no unexpected toxic effects were observed. Capecitabine as third-line treatment showed a favourable toxicity profile, but exhibited low activity in patients with advanced renal cell carcinoma after failing immunotherapy.


Assuntos
Antimetabólitos Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Desoxicitidina/análogos & derivados , Fluoruracila/análogos & derivados , Neoplasias Renais/tratamento farmacológico , Administração Oral , Idoso , Antimetabólitos Antineoplásicos/administração & dosagem , Antimetabólitos Antineoplásicos/efeitos adversos , Capecitabina , Carcinoma de Células Renais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/uso terapêutico , Progressão da Doença , Relação Dose-Resposta a Droga , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/uso terapêutico , Humanos , Imunoterapia , Neoplasias Renais/patologia , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Pró-Fármacos , Indução de Remissão , Taxa de Sobrevida , Falha de Tratamento
17.
BJU Int ; 100(4): 775-9, 2007 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-17535276

RESUMO

OBJECTIVE: To evaluate the activity and tolerability of weekly high-dose calcitriol and docetaxel in patients with metastatic hormone-refractory prostate cancer (HRPC) previously exposed to docetaxel, as patients who progress after docetaxel treatment might be considered for second-line chemotherapy, but with no standard salvage therapy available we hypothesised that high-dose calcitriol might restore sensitivity to chemotherapy. PATIENTS AND METHODS: The study comprised 26 patients who had progressed after first-line treatment with docetaxel-based chemotherapy had failed. Treatment cycles consisted of calcitriol (32 microg orally as 0.5 microg tablets) on day 1 and docetaxel (30 mg/m(2) intravenous) on day 2, administered for six consecutive weeks followed by a 2-week rest interval for a maximum of 24 cycles. RESULTS: There was a response in prostate-specific antigen (PSA) level in eight patients (31%); seven (27%) had a stable PSA level for >/= 12 weeks. The median time to PSA progression was 4.2 months and the median survival was 9.3 months. The regimen was generally well tolerated; there was grade 2 hypercalcaemia, probably related to calcitriol, in one patient after six treatment cycles. CONCLUSION: Weekly high-dose calcitriol and docetaxel seems to be an effective and well-tolerated treatment option for patients with metastatic HRPC previously exposed to docetaxel-based chemotherapy.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Idoso , Calcitriol/administração & dosagem , Progressão da Doença , Docetaxel , Esquema de Medicação , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Metástase Neoplásica , Antígeno Prostático Específico/sangue , Taxoides/administração & dosagem , Resultado do Tratamento
18.
Oncology ; 70(5): 345-50, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-17179728

RESUMO

OBJECTIVE: Patients with metastatic colorectal cancer (MCC) usually receive FOLFOX-4, or other oxaliplatin (L-HOP)-based regimens, until the occurrence of progressive disease, with an increase in the incidence of neurotoxicity which is correlated to the cumulative dose of L-HOP. The aim of this study was to evaluate if FOLFOX-4 stop and go and capecitabine maintenance chemotherapy is associated with a low incidence of severe neurotoxicity in the treatment of MCC patients. METHODS: Thirty-three patients were treated with FOLFOX-4 (L-HOP 85 mg/m(2) day 1, leucovorin 200 mg/m(2), 5-fluorouracil bolus 400 mg/m(2) and 22 h 600 mg/m(2) days 1 and 2, every 2 weeks). Patients who achieved objective response (OR) or stable disease (SD) then received oral capecitabine 2,500 mg/m(2) days 1-14 every 3 weeks; L-HOP was reintroduced as soon as progression occurred. RESULTS: Twenty-eight of the 29 patients who achieved OR or SD then received capecitabine. FOLFOX-4 was reintroduced in 18 patients (56.2%). The median response duration (RD) was 9.2 months and median progression-free survival (PFS) was 8.6 months. Twenty-eight patients (87.5%) had peripheral neuropathy during treatment, but grade 3 neurotoxicity was observed in only 1 patient (3.1%). CONCLUSIONS: FOLFOX-4 stop and go and capecitabine maintenance chemotherapy was associated with a very low incidence of grade 3 neurotoxicity. Although the number of patients enrolled was far too low for a definite conclusion, RD and PFS were comparable to those usually reported in the treatment of MCC patients.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Colorretais/tratamento farmacológico , Sistema Nervoso/efeitos dos fármacos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Capecitabina , Neoplasias Colorretais/patologia , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Desoxicitidina/análogos & derivados , Esquema de Medicação , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Fluoruracila/análogos & derivados , Humanos , Incidência , Leucovorina/administração & dosagem , Leucovorina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Doenças do Sistema Nervoso/induzido quimicamente , Compostos Organoplatínicos/administração & dosagem , Compostos Organoplatínicos/efeitos adversos , Índice de Gravidade de Doença , Resultado do Tratamento
19.
J Cutan Pathol ; 33(2): 181-4, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16420316

RESUMO

Adenocarcinoma of the rete testis (ACRT) is extremely rare and has only been the subject of sporadic case reports, in most of which the neoplasm manifested as a scrotal mass with diffuse enlargement of the testis. Only a few cases of scrotal infiltration by a contiguous ACRT have been described. To our knowledge, none have reported distant skin metastases. We report a case of ACRT presenting with suprapubic skin metastases. The diagnosis was based on clinical and histopathological findings and supported by the results of immunohistochemical and ultrastructural studies. We discuss the differential diagnosis to this rare entity, which include metastatic adenocarcinoma, serous tumor of the testis, and mesothelioma of the tunica vaginalis.


Assuntos
Adenocarcinoma/secundário , Rede do Testículo/patologia , Neoplasias Cutâneas/secundário , Neoplasias Testiculares/patologia , Adenocarcinoma/ultraestrutura , Idoso , Humanos , Masculino , Microscopia Eletrônica de Transmissão , Neoplasias Cutâneas/ultraestrutura
20.
Hepatogastroenterology ; 52(65): 1626-30, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16201130

RESUMO

BACKGROUND/AIMS: The aim of this study was to evaluate the survival benefit of adjuvant chemotherapy with etoposide, leucovorin and 5-fluorouracil (ELF) in gastric cancer patients undergoing previous surgery with a curative intent. METHODOLOGY: The clinical outcome of 49 patients with resected gastric cancer treated with adjuvant chemotherapy was compared with that of 85 surgically treated historical controls who did not receive any adjuvant treatment. The chemotherapy regimen consisted of six cycles of daily 1-hour intravenous infusions of folinic acid 100 mg/m2 and 5-FU 400 mg/ m2, and a 2-hour infusion of etoposide 100 mg/m2, for three days every 28 days. RESULTS: The 5-year relapse-free survival was 32% in the adjuvant arm and 27% in the control arm (p = 0.6). At the last follow-up, there were 32 deaths in the adjuvant arm and 60 in the control arm. The median duration of survival was respectively 23 and 19 months, and the 5-year survival rates were 34% and 29% (p = 0.4). The chemotherapy was well tolerated. CONCLUSIONS: Our data suggest that ELF adjuvant treatment is a safe and well tolerable combination chemotherapy in patients with resected gastric cancer, but it does not seem to improve prognosis in comparison with historical controls.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/cirurgia , Quimioterapia Adjuvante , Etoposídeo/uso terapêutico , Feminino , Fluoruracila/uso terapêutico , Gastrectomia , Humanos , Leucovorina/uso terapêutico , Levoleucovorina , Masculino , Pessoa de Meia-Idade , Neoplasias Gástricas/mortalidade
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