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H H Hansen

Publications and source records attributed to H H Hansen.

At least 55 records · Page 3Linked to original sources
PubMed1999

The European Society for Medical Oncology (ESMO) and its activities through the Central Eastern European Task Force.

The article describes the history and organization of the European Society for Medical Oncology. The society, founded in 1975, aims at advancing medical oncology on a pan-European basis. Postgraduate training and education constitute a major part of ESMO's activities through a current CME programme of courses and other activities. Each year the ESMO Examination is held, and every other year ESMO organizes its congresses with the latest attendance of more than 6000 delegates. ESMO has a continuous increase of members, also from outside Europe. In 1996 ESMO created the Central Eastern European Programme with the aim to support the needs of the countries of the former Eastern Europe. A task force (CEE TF) with members from 16 Central Eastern European countries meets twice a year to discuss key areas. An e-mail communication system has been launched, courses are planned for 1998-1999, exchange programmes are in progress, and support in setting up national guidelines will follow. A Central Eastern European Oncology Group (CEE OG), which performs clinical trials on a cooperative basis, has been established with ESMO guidance.

Clinical Trials as Topic↗
PubMed1999

Lung cancer.

The results of the many clinical trials published in 1997 had only modest impact on the treatment results using either cytostatic agents alone or combined with radiotherapy in lung cancer. In SCLC, combination chemotherapy including platin-compounds (cisplatin, carboplatin) and the podophyllotoxins (etoposide and teniposide) continue to be the cornerstone of therapy. Complete plus partial responses to combination chemotherapy occurs in 80-90% of all patients. Median survival is at present 11-17 months, and overall 5-year survival approximately 5% depending on the initial tumor stage. The duration of treatment has been shortened to 5-6 months. In relapsing patients topotecan and paclitaxel appear to have clinical useful activity. For epidermoid, adeno- and large cell carcinoma further support has arisen for the use of preoperative and preirradiatory chemotherapy in stage III NSCLC, but further studies are needed before specific recommendations can be given for general use. For patients with advanced NSCLC, new innovative treatments are still urgently needed. Platin-containing regimens with the inclusion of new agents, such as gemcitabine, taxenes, and navelbine, yielded response rates of 42-55% in phase II trials, but results from large phase III trials are necessary in order to measure the impact of these new agents in the management of NSCLC. Major improvements of therapy for mesothelioma have not occurred within the last year.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

[Percutaneous transluminal coronary angioplasty in acute myocardial infarction. A prospective controlled study].

In the present study we compared the outcome of primary percutaneous coronary angioplasty (PTCA) (PTCA without prior or concomitant administration of thrombolytic drugs) in 82 consecutive patients with acute myocardial infarction (AMI) with the outcome of 82 AMI patients, who were treated with intravenous thrombolysis. The thrombolysis patients were prospectively matched to the angioplasty patients regarding age, sex, duration of symptoms and infarct localisation. The in-hospital mortality was 3.7% in the PTCA group versus 4.9% in the thrombolysis group. Thrombolysis-treated patients had increased use of diuretics and ACE-inhibitors as compared to PTCA-treated patients. The mean ejection fraction was 52 +/- 11% in the PTCA group versus 47 +/- 10% (p = 0.01) in the thrombolysis group. We conclude that initial Danish experience with primary PTCA is promising, and that this treatment may favourably affect the outcome of acute myocardial infarction.

Aged↗
PubMed1998

Long-term effects on serotonin transporter mRNA expression of chronic neonatal exposure to a serotonin reuptake inhibitor.

Chronic administration of clomipramine or other serotonin (5-hydroxytryptamine, 5-HT) reuptake inhibitors to neonatal rats produces behaviours that resemble a depressive state in the adult animal, and this model is therefore regarded as a putative animal model of depression. Alterations in the activity of the central 5-HT system are important in understanding the pathophysiology of depression, and therefore, we examined whether this model was associated with changes in the expression of 5-HT1A receptor, 5-HT1B receptor, and 5-HT transporter mRNA in the dorsal raphe nucleus and the hippocampus. Wistar rats were injected twice daily with the serotonin reuptake inhibitors clomipramine and 5-chloro-1-[3-(dimethylamino)propyl]-1-(4-fluoro-phenyl)-1,3-dihydroi so-benzofurane, hydrochloride (code Lu 10-134-C) at doses of 15 mg kg(-1) or vehicle i.p. from postnatal day 8 for 14 days. Groups of rats (n = 10) were either killed the day after the last injection or left undisturbed for 69 days before they were killed. The expression of 5-HT transporter, 5-HT1A receptor, and 5-HT1B receptor mRNA was examined in the dorsal raphe nucleus and in the CA1 of the hippocampus by means of quantitative in situ hybridisation histochemistry. Both compounds resulted in an increase in 5-HT transporter mRNA expression (40% more than vehicle) in the dorsal raphe nucleus the day after the last injection (postnatal day 22). A small but significant increase in 5-HT1B receptor mRNA expression in the CA1 was seen after clomipramine, but not after Lu 10-134-C, probably reflecting clomipramine's affinity for both the 5-HT and noradrenaline transporters as well as for a number of monoamine receptor sites. Levels of 5-HT1A receptor mRNA were unchanged. In contrast, 5-HT transporter mRNA expression in the dorsal raphe nucleus was significantly decreased in the adult after neonatal treatment with either of the two drugs compared to vehicle. No changes in 5-HT1A receptor and 5-HT1B receptor mRNA expression were observed in any of the regions examined in these animals. The results show that the persistent depressive behaviour previously shown in this model is also associated with changes in the expression of 5-HT transporter mRNA. This long-term alteration in gene expression may result from disturbances in 5-HT neurotransmission in the brain of the neonatal animals.

Animals↗
PubMed1998

Formation of N-acyl-phosphatidylethanolamines and N-acetylethanolamines: proposed role in neurotoxicity.

The formation of N-acyl-phosphatidylethanolamine (NAPE) and N-acylethanolamine (NAE), including anandamide, in mammals in relation to neurotoxicity is discussed. Data on the characterization of the NAPE-forming N-acyltransferase, the NAPE-hydrolyzing phospholipase D, and the NAE-hydrolyzing amidase are reviewed. We suggest that NAPE and NAE, including anandamide, are formed in neurons in response to the high intracellular calcium concentrations that occur in injured neurons, e.g. due to glutamate excitotoxicity. NAPE may have functions of its own besides being a precursor for NAE. The formation of both of these lipids may serve as a cytoprotective response, whether mediated by physical interactions with membranes or enzymes, or mediated by activation of cannabinoid receptors. This suggestion implies that NAPE and NAE may have pathophysiological roles in the brain. Whether these lipids also have physiological roles is uncertain.

Amidohydrolases↗
PubMed1998

Randomized, double-blind comparison of granisetron versus granisetron plus prednisolone as antiemetic prophylaxis during multiple-day cisplatin-based chemotherapy.

Ninety chemotherapy-naive cancer patients receiving cisplatin-based (> or = 50 mg/m2) chemotherapy participated in a randomized, double-blind, cross-over study comparing the safety and efficacy of granisetron (GRA) versus granisetron plus prednisolone (GRA + PRE). All patients received i.v. granisetron 3 mg and were randomly allocated to oral prednisolone 50 mg or placebo prior to chemotherapy. At the subsequent cycle of chemotherapy, patients were crossed over to the other antiemetic treatment. A complete response, defined as no emetic episodes and no worse than mild nausea, was obtained in 63% in the GRA group and in 79% of the patients in the GRA + PRE group day 1 (P = 0.013). Complete response rates on days 1-3 were 16% vs 27% (P = 0.251). Significantly less nausea and vomiting was seen with the combination in the first 24 h after cisplatin (P = 0.001 and P = 0.0003) and during days 1-3 (P = 0.005 and 0.044). Patient preference was 51.5% for the combination and 26.5% for granisetron alone, whereas 22% had no preference (P = 0.0270). Adverse reactions were mild and comparable; headache and constipation were the ones most frequently reported. Prednisolone significantly improves the antiemetic effect of granisetron in patients receiving cisplatin-based chemotherapy, but the study also emphasizes the poor complete protection rate in patients receiving multiple-day cisplatin-based chemotherapy.

Adult↗
PubMed1998

The ESMO programme of certification and training for medical oncology.

ESMO has designed a programme of certification and training in medical oncology. In this paper the background of these programmes is given, and the programme of graduate education is described in greater detail. The standard requirements are a total training period of six years, beginning with a common internship in internal medicine of at least two years, followed by a training programme in oncology for three to four years, which must include at least one year of full-time clinical training in the diagnosis and management of neoplastic diseases, accompanied by one year of experience in an ambulatory care setting.

Certification↗
PubMed1998

Current therapy of small cell lung cancer.

This article reviews the most important recent clinical trials on the treatment of small cell lung cancer (SCLC). Two randomized studies addressing the timing of thoracic radiotherapy in limited stage SCLC are discussed. In the smaller of the two studies (n = 103), a survival benefit was associated with initial versus delayed radiotherapy. No survival differences in the larger study of the two studies were detected, which compared alternating with sequential delivery of radiotherapy (n = 335). The optimal way to deliver radiotherapy still must be defined. Two small, randomized studies on dose intensity with the use of growth factor support in patients with extensive disease reached conflicting results. Two randomized trials including patients with poor prognosis were discontinued prematurely, owing to interim analyses reporting a significant disadvantage in survival associated with oral single-agent etoposide compared with intravenous multiagent treatment. Thus, oral etoposide has a very limited role as single-agent treatment in the palliative setting. Convincing data have emerged regarding the camptothecins. Randomized studies of both the camptothecins and the taxanes in combination with established drugs are awaited with interest. Unfortunately, too many studies still lack sufficient statistical power, and large randomized studies are needed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1997

Phase II trial of high-dose cisplatin plus ifosfamide as first-line followed by carboplatin as second-line treatment in epithelial ovarian carcinoma.

BACKGROUND: In a previous study of combined platinum and ifosfamide we found a pathologic complete response rate of 42%. The present study was to test whether the high response rate could be reproduced or even improved by combining high-dose cis-platinum and increased dose of ifosfamide. METHODS: Forty-two previously untreated ovarian cancer patients were included in the study. Cisplatin 50 mg/m2 and ifosfamide 2000 mg/m2 together with mesna 1200 mg/m2 were given daily, Day 1-3 every 4 weeks for six cycles, followed by second-look laparotomy. In the event of residual disease carboplatin was given every 4 weeks for a further six cycles. RESULTS: The pathologic complete response rate was 20% (8 of 41). Five of 26 patients achieved a further response on carboplatin. Hematologic and nonhematologic toxicity caused dose reduction in more than 90 and 50% of the patients, respectively. CONCLUSION: The results of this high-dose regimen equals those obtained with conventional, far less toxic, regimens. Only patients with potentially platinum-sensitive tumors achieved further response when crossed over to the analogue, which may indicate that prolonged treatment is better than increased dose. A randomized trial is still needed to assess the importance of dose intensity in ovarian cancer.

Adult↗
PubMed1997

Elevated plasma levels of urokinase plasminogen activator receptor in non-small cell lung cancer patients.

The urokinase plasminogen activator (uPA) is involved in extracellular matrix degradation during cancer invasion. Binding of uPA to a specific cell surface receptor (uPAR) is a key step in this process. We have previously reported that high levels of uPAR in squamous cell lung cancer tissue extracts are associated with poor prognosis (Pedersen et al., Cancer Res 1994, 54, 4671-4675). Recently we found that uPAR is present in blood plasma from healthy donors as determined by enzyme-linked immunosorbent assay (ELISA) and chemical cross-linking. We now report that uPAR in plasma from 17 patients with non-small cell lung cancer (NSCLC) was significantly higher than in 30 healthy controls (P = 0.0004), while no significant increase was found in plasma from 14 patients with small cell lung cancer (SCLC). The increased levels of uPAR in the plasma from NSCLC patients is likely to be due to release of uPAR from the tumour tissue, and may, therefore, be related to prognosis.

Biomarkers, Tumor↗
PubMed1997

Early clinical investigation of sulofenur with a daily schedule in advanced solid tumours.

Sulofenur, a sulfonylurea, has demonstrated antitumour effect in preclinical studies. A phase I trial was initiated to study the clinical aspects. Sulofenur was given p.o. daily for a period of 28 days in 5-week courses. The initial dosage was 250 mg/m2 escalating to 700 mg/m2 daily with no dose modification for the individual patient at any given dose level; 38 patients with advanced solid malignant tumours were enrolled. Haemolytic anaemia was the main side effect. The toxicity was marked at dose levels of 600 and 700 mg/m2. Moderate methaemoglobinaemia also occurred. One case of reversible toxic hepatitis was observed. Generally was ALAT, and more moderately basic phosphatases, and LDH elevated. Tumour regression was not observed but one patient had stable disease throughout nine courses. The maximal detected plasma concentration of Sulofenur in this study was 348 x 10(-6) g/ml. In the present study the maximum tolerated dose (MTD) of Sulofenur was defined to 600 mg/m2. One conclusion from this study is that even at doses above that recommended for future studies-5-600 mg/m2-with this schedule, the suggested effective plasma level from preclinical studies could not be reached. The overall conclusion is that this schedule should not be recommended at all for future studies and the recommendation should be to try to find a schedule in which higher plasma levels can be achieved at a clinically tolerated dose.

Adult↗
PubMed1997

Efficacy of single-agent gemcitabine in advanced non-small cell lung cancer: a review.

Within the last 5 years, gemcitabine, a new nucleoside analogue, has been evaluated in several international phase II trials in patients with advanced non-small cell lung cancer (NSCLC). Five trials have evaluated 438 patients. Gemcitabine was administered intravenously in four trials on days 1, 8, and 15 at a dose of 800 to 1,700 mg/m2 every 4 weeks. In the fifth trial, gemcitabine was given at a dose of 90 mg/m2 twice weekly x 3 every 4 weeks. The overall response rate was 21% (95% confidence limits, 16% to 25%) with a median survival of 4 weeks (range, 26 to 46 weeks). The median duration of response varied from 26 to 49 weeks. The activity of gemcitabine in NSCLC, together with its modest toxicity and distinct mode of action, suggest the need for further trials of gemcitabine in combination with other chemotherapeutic agents in the treatment of NSCLC.

Antimetabolites, Antineoplastic↗
PubMed1997

Neonatal administration of the selective serotonin reuptake inhibitor Lu 10-134-C increases forced swimming-induced immobility in adult rats: a putative animal model of depression?

Chronic administration of the tricyclic antidepressant clomipramine to neonatal rats from postnatal days 8 to 21 is reported to induce several behavioral changes in adult life, and it may serve as an animal model of human depressive disorder. Findings include increased immobility time in the forced swim test and locomotor hyperactivity in the open field test. Clomipramine is a serotonergic reuptake inhibitor, which suggests that altered development of the serotonergic system could account for the observed behavioral changes in the adult rat. The present study was carried out with a selective serotonin reuptake inhibitor (SSRI) to investigate whether the serotonin system, in particular, is involved in the neonatal animal model. The substance, Lu 10-134-C (LU), was characterized in monoamine reuptake and receptor binding assays and found to be an SSRI. Rats received LU during postnatal days 8 to 21 (2.5-15 mg/kg b. i.d.), and they were assessed in open field, forced swim and social interaction tests at the age of 4 months. Behavior of LU-treated rats and saline controls did not differ in the open field and social interaction tests. However, in the forced swim tests LU-treated neonates showed prolonged immobility time compared with saline controls. In conclusion, chronic LU treatment during neonatal life produces long-term changes in the forced swim test, but not in the open field and social interaction tests. The behavioral changes in the forced swim test suggest that the central serotonergic system may be involved in the putative neonatal animal model of depression.

Animals↗
PubMed1997

Lung cancer.

In small cell lung cancer (SCLC) combination chemotherapy including agents such as etoposide, teniposide, cisplatinum, carboplatin, and vincristine, doxorubicin, and cyclophosphamide, or ifosfamide continues to be the back-bone of therapy. The epipodophyllotoxin derivatives together with cisplatin or carboplatin are being used increasingly as part of the initial therapy, and these combinations are by most investigators considered standard therapy. Complete plus partial responses to combination therapy occur in 80-90% of all patients with a median duration of 9-12 months. The median survival in these studies is at present 11-18 months depending on the initial tumour stage. The 5-year survival data remain still around 5% including a small fraction of patients (2%) initially presenting with extensive disease. The tendency is to shorten the duration of treatment to 5-8 months. The results of intensifying the treatment with the use of haematopoietic growth factors continue to be disappointing, although these are not conclusive. With respect to squamous cell carcinoma, adenocarcinoma, and large cell carcinoma several meta-analyses indicate that there is a statistically significant, albeit small advantage favouring cisplatinum containing chemotherapy when added to surgery in stage I and II disease and to radiotherapy in stage III NSCLC. Similarly, cisplatin containing chemotherapy is statistically superior to best supportive care in stage IV disease. The results from the latter analyses are significant at 1 and 2 years, respectively, but not at 3 and 5 years of survival. These data must, however, be considered in the light of their clinical relevance and of the balance between quality of life, toxicity, and cost of chemotherapy. The results of recently published phase III trials in stage III disease support the use of combined modalities of chemotherapy and radiotherapy versus radiotherapy alone. For both small cell and non-small cell lung cancer a number of new agents have been evaluated over the last 2 to 3 years and among those navelbine, topotecan, gemcitabine, and taxanes (taxol and taxotere) have yielded the most encouraging results. For mesothelioma the therapeutic results are unchanged, and no standard chemotherapy has yet been developed.

Carcinoma, Non-Small-Cell Lung↗