1,721,170 research outputs found
The clinical management of early and advanced colorectal cancer
No full textDespite the impressive developments in the fields of preclinical research and chemoprevention of colorectal cancer, this disease remains the second most common cause of cancer death after lung cancer in the western hemisphere. Things are moving along, however, and it is common opinion that the medical treatment of colorectal cancer is the field of Medical Oncology where the most signifcant advances have been achieved in the last 10 years. The value of adjuvant chemotherapy for colorectal cancer has been confirmed in several randomized trials and it has been firmly established that systemic chemotherapy doubles the survival of patients with advanced colorectal cancer compared to untreated controls. In addition, for the first time in 40 years since 5-fluorouracil development, there seem to be valuable alternatives/ adjuncts to the fluoropyrimidines. The management of individual patiens, however, remains a very challenging matter both in the adjuvant and the advanced setting. In this connection, no rigid guidelines can be given, as too many factors play crucial roles in the clinical decision-making. The purpose of this article is reviewing the evidence to suggest the most appropriate treatment for each condition
Role of oxaliplatin in the treatment of colorectal neoplasias [Ruolo dell'oxaliplatino nel trattamento delle neoplasie del colon-retto]
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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
Mechanism of action of fluoropyrimidines: Relevance to the new developments in colorectal cancer chemotherapy
No full textAlternating 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
Information given to cancer patients on diagnosis, prognosis and treatment: the clinical oncologist's perspective
No full textMechanism of action of fluoropyrimidines: relevance to the new developments in colorectal cancer chemotherapy
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