1,720,974 research outputs found
The role of systemic chemotherapy in the treatment of brain metastases from small-cell lung cancer
No full textBrain is the most common site of metastatic spread in small-cell lung cancer (SCLC). Approximately 10% of SCLC patients have brain metastases (BM) already at diagnosis and an additional 40% will develop central nervous system (CNS) involvement during their disease course. Although whole brain radiotherapy and corticosteroids is considered the treatment of choice, accumulating evidence suggests that systemic chemotherapy may also play an important role. The concept of the brain as a pharmacologic sanctuary site for established metastases is in contrast with recent clinical observations of frequent BM responses with systemic chemotherapy. During the last decade, several reports about the effect of systemic chemotherapy on BM from SCLC have been published. Pooled data from five studies report 66% response rate (RR) in 64 patients with initial BM. In addition, an average RR of 36% is derived from five studies including 135 patients with delayed BM treated with systemic single agent chemotherapy. Among new drugs with activity in patients with SCLC brain metastases, camptothecin analog topotecan is one of the most promising with a 52% RR. Although whole brain radiation remains the standard treatment of established BM in SCLC there is an emerging role for systemic chemotherapy, particularly with the use of new active drugs as part of combined modality treatments
Alternating bolus and continuous infusion 5-fluorouracil: A strategy to overcome resistance to this fluoropyrimidine in advanced colorectal cancer patients
No full textFocusing our effort on the importance of FUra scheduling we have tested the hypothesis that pulse and continuous
infusion (CI) of the fluoropyrimidine have different mechanisms of cytotoxicity. Our initial approach was to compare
the mechanism of resistance of a cell line resistant to a short term exposure to FUra (HCT-8/FU4hR) to that of a
cell line resistant to a prolonged exposure to the fluoropyrimidine (HCT-8/FU7dR). Cytotoxicity studies showed
that HCT-8/FU4hR cells were still sensitive to FUra given as a 7-d exposure, suggesting different mech~misms
of resistance. Indeed, rapid recovery of TS activity after drug removal was evident in the HTC-8/FU7dR cell
line while HCT-8/FU4hR cells were similar to the parental cell line with regard to both the degree of in situ TS
inhibition by FUra and duration of inhibition after FUra removal. In contrast, labelling studies with [3H-6] FUra (4
h exposure, 100 # M) showed that the incorporation of the fluoropyrimidine into RNA is significantly decreased in
HCT-8/FU4hR cells as compared to parental HCT-8 cells.
Given the lack of cross resistance between the two schedules in vitro, a pilot trial was done on patients with
colorectal cancer refractory to bolus FUra. On 15 patients failing after FUra+LV or FUra alone 1 PR, 3 MR,, 3 SD
and 8 P were observed, confirming a certain degree of activity of CI FUra in patients clinically resistant to bolus
FUra.
Based on this rationale, a phase II trial of schedule-oriented biochemical modulation of FUra in advanced
colorectal cancer patients was conducted, employing a hybrid regimen of 2 biweekly cycles of FUra bolus (600
mg/sqm), preceeded by (24 h interval) methotrexate, 200 mg/sqm (in order to maximize the RNA effect of the drug)
alternating with FUra continuous infusion, 200 mg/sqm daily for 3 weeks, modulated by leucovorin, 20 mg/sqm
weekly bolus (in order to maximize the DNA effect).
Thirty-three consecutive patients (median ECOG PS 1) with advanced measurable colorectal cancer and no prior
therapy for metastatic disease entered the study, from February 1992 to August 1993. Three complete and 13 partial
responses were obtained among these 33 patients (RR=48%, 95% confidence limis, 31-66%). After a median
follow-up time of 23 months, 16 patients are still alive. The median progression free survival and overall survival
were 9.6 and 20.8 months, respectively. No toxic deaths or grade 4 toxicity occurred. The incidence of grade 3
toxicity per patient in any cycle was: mucositis 6%, diarrhea 3% and vomiting 3% for the bolus part and 21%, 3%
and 6% respectively, for the continuous infusion part of the regimen. Hand-foot syndrome occurred in 27% ,of the
patients treated with the continuous infusion regimen.
In conclusion, this experimental and clinical project has generated a novel regimen of schedule oriented biochemical modulation that is twice as active and half as toxic compared to bolus FU+LV given with either the daily x
5 or the weekly schedule. This high clinical activity is very encouraging, especially considering that 1) consecutive
patients were entered, 2) the responses were independently reviewed, 3) the progression free survival and survival
were much longer than those actually reported for this disease, 4) the toxicity of the program, in particular the bolus
regimen, was relatively low allowing further intensificatio
Management of malignant pleural effusions
No full textMalignant pleural effusions (MPEs) represent a common complication of advanced malignancies. However, adequate palliation of this highly symptomatic accompaniment to cancer can be achieved in most patients by adopting the appropriate therapy. Several options are available for the treatment of MPE. Systemic therapy may control the effusion in patients whose underlying malignancy is sensitive to anticancer agents. Repeated thoracocentesis can be appropriate for patients with limited life expectancy or slowly recurrent effusions. In the majority of the remaining cases the treatment of choice is pleurodesis with sclerosing agents administered via tube thoracostomy. Controversy still exists as to which drug produces the best results: talc and bleomycin appear to be among the most cost-effective agents. The debate over the best agent to be used for pleurodesis refers to the difficulty in comparing results of studies using different eligibility criteria, response assessment and end-points. This article describes the various treatments which have been reported in the literature to play a role in the management of MPEs. It is also aimed at providing guidelines in allocating patients to appropriate treatments
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Activity of continuous-infusion 5-fluorouracil in patients with advanced colorectal cancer clinically resistant to bolus 5-fluorouracil.
No full textWe have recently demonstrated that continuous-infusion (CI) 5-fluorouracil (FU) eradicates human colon carcinoma cells made resistant to bolus FU in vitro. In addition, in the same experimental system, the mechanisms of resistance to pulse and CI FU were found to be different. These observations led us to test the clinical activity of a standard regimen of CI FU (300 mg/m2 per day) in a cohort of 15 patients with advanced measurable colorectal cancer who were in progression after having failed to respond to bolus treatment with FU alone (3 patients) or FU combined with high-dose 6-S-leucovorin (LV) (12 patients). The median age of the patients was 68 years, and their median Eastern Cooperative Oncology Group performance status (ECOG PS) was 1. No myelotoxicity was observed. Mild diarrhea, mucositis, and vomiting occurred in 32%, 26%, and 19% of the patients, respectively, with no WHO grade 3 or 4 episodes being noted. In all, 6 of 15 patients complained of hand-foot syndrome, which was severe in 2 instances, lasting approximately 1 week. Overall, 1 partial response and 6 instances of disease stabilization, including 3 minor responses, were obtained both in patients who had been pretreated with pulse FU alone and in patients who had failed first-line treatment with FU + LV. Finally, 8 patients failed CI FU. In conclusion, these results, obtained in patients who were clearly progressing after having failed first-line treatment, support our experimental finding that resistance to bolus FU may be overcome by CI FU and extend this possibility to patients who are resistant to bolus treatment with FU + LV
Appropriate Similarity Measures for Author Cocitation Analysis
Full text linkWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
The combination of etoposide and cisplatin in non-small-cell lung cancer (NSCLC)
No full textThe role of chemotherapy in the treatment of advanced non-small-cell lung cancer (NSCLC) has been a subject of debate for many years. Only recently, cisplatin-based combination chemotherapy has been demonstrated to yield a small but definite survival benefit and to improve symptoms, performance status and quality of life in a substantial proportion of advanced NSCLC patients. The cisplatin-etoposide (PE) regimen was developed in the early 1980s and has been one of the standard chemotherapy programs most extensively used in the clinical practice until a few years ago. More recently, several randomized trials have compared the efficacy of new cisplatin-containing combination chemotherapies including Paclitaxel or Gemcitabine with that of PE or PE-like regimens. Preliminary results are encouraging, indicating a small benefit in favor of the last generation of regimens which might therefore replace PE as 'gold standards' in the treatment of advanced NSCLC. However, the costs of these last generation regimens is higher and the entity of the benefit small. Therefore, PE chemotherapy can still be an option in selected situation
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