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PubMed2002

Interaction of high concentrations of riluzole with recombinant skeletal muscle sodium channels and adult-type nicotinic receptor channels.

Riluzole is a neuroprotective drug that modulates glutamergic transmission but also blocks the inactivated state of voltage-gated neuronal sodium channels at very low concentrations (about 0.1 microM). After nausea, the most common adverse effect of riluzole is asthenia, which could be due to a block of muscle sodium channels or acetylcholine receptor channels. Using the patch-clamp technique, we applied riluzole on recombinant voltage-gated skeletal muscle sodium and adult nicotinic acetylcholine receptor channels expressed in a mammalian cell line (HEK 293). Riluzole blocked the inactivated state of voltage-gated skeletal muscle sodium channels, shifting the midpoint of the steady-state inactivation curve to more negative potentials, but only in comparatively high concentrations (> or = 0.1 mM). At these concentrations, riluzole also caused an open-channel block at acetylcholine receptor channels. We conclude that riluzole has only a mild blocking effect on the inactivated state of voltage-gated skeletal muscle sodium channels and nicotinic acetylcholine receptor channels. As the plasma concentration of riluzole in amyotrophic lateral sclerosis (ALS) patients approximates 2 microM, it seems unlikely that asthenia is caused by a block of skeletal muscle sodium channels or acetylcholine receptor channels by riluzole.

Dose-Response Relationship, Drug↗
PubMed1996

Phase II study of elsamitrucin (BMY-28090) for the treatment of patients with refractory/relapsed non-Hodgkin's lymphoma.

PURPOSE: To determine the response rate of patients with refractory/relapsed non-Hodgkin's lymphoma to treatment with elsamitrucin and to further characterize the toxic effects of elsamitrucin in this group of patients. PATIENTS AND METHODS: Eligibility required pathologically verified relapsed or refractory non-Hodgkin's lymphoma with no more than two prior chemotherapy regimens for patients with tumors classified by the International Working Formulation (IWF) as A-C and no more than one prior chemotherapy for those with IWF grades D-G. Patients were entered with either normal or impaired bone marrow function, but normal liver function tests were required unless clearly related to lymphomatous involvement of the liver. Elsamitrucin 25 mg/m2 was administered intravenously over 5-10 minutes weekly. RESULTS: Thirty-one patients entered the study and were treated for a median of six weeks (range 1-42). All patients were evaluable for toxicity and 30 for response. Mild nausea and/or vomiting and asthenia were the most frequently reported adverse events. Four (13%, 95% Cl 4.4-31.6%) partial responses were seen along with two (7%) minor responses while 9 (30%) patients had stable disease. CONCLUSION: Elsamitrucin showed modest activity in patients with relapsed or refractory non-Hodgkin's lymphoma. Toxicity was relatively mild, consisted mainly of asthenia, nausea and vomiting and did not include myelosuppression. The activity of elsamitrucin in this group of patients and its lack of myelosuppression suggest utility in this disease especially when combined with other proven agents.

Adult↗
PubMed2005

Exocrine pancreatic cancer: symptoms at presentation and their relation to tumour site and stage.

INTRODUCTION: The need to detect pancreatic cancer at earlier stages is undisputed. We recorded the signs and symptoms of patients presenting with exocrine pancreatic cancer and evaluated their association with clinical characteristics such as tumour site and disease stage. PATIENTS AND METHODS: All patients (n = 185) with exocrine pancreatic cancer newly diagnosed at five general hospitals in Eastern Spain were prospectively recruited over 5 years. Symptoms were elicited through personal interviews and signs were recorded by the attending physician on admission. RESULTS: At diagnosis, one third of tumours of the pancreas head were in stage I and another third in stage IV. None of the tumours of the body and tail were in stage I, and over 80% were in stage IV (p < 0.001) . At presentation, the most frequent symptoms were asthenia (86%), anorexia (85%), weight-loss (85%), abdominal pain (79%), and choluria (59%). Cholestatic symptoms were more common in tumours affecting only the pancreatic head (p < 0.001) . There was a clear trend toward more localized tumours with increasing numbers of cholestatic signs (p < 0.001) . Asthenia, anorexia and weight-loss were unrelated to stage. An increased symptom-to-diagnosis interval was associated with more advanced stage (p = 0.048). CONCLUSIONS: Proper attention to signs and symptoms, especially cholestasis, may help identify patients with pancreatic cancer at an earlier stage. Results also provide a current picture of the semiology of pancreatic cancer which could be of use in studies on the potential of proteomic tests in the early detection of this neoplasm.

Aged↗
PubMed2000

Phase I/II dose escalation study of docetaxel and carboplatin combination supported with amifostine and GM-CSF in patients with incomplete response following docetaxel chemo-radiotherapy: additional chemotherapy enhances regression of residual cancer.

Taxanes have been shown to interact with anti-apoptotic proteins. In the present study we investigated whether the addition of taxane in combination with DNA damaging drugs can further enhance tumor shrinkage in cases with incomplete response to radiotherapy. Since the dose of docetaxel in combination with carboplatin is not known, the above hypothesis was tested in the context of a dose escalation phase I study. Twenty-eight patients with locally advanced chest or pelvic tumors, showing residual disease on CT scans performed 40 d following docetaxel radio-chemotherapy, were recruited in a dose escalation protocol of docetaxel/carboplatin supported with amifostine and GM-CSF. The starting dose of docetaxel was 40 mg/m2 every 2 weeks. Carboplatin dose was calculated using the Calvert formula and was escalated in cohorts of 4 patients (starting dose AUC2 every two weeks; AUC0.5 increments up to AUC3). Thereafter the docetaxel dose was increased to 50 and 60 mg/m2, while carboplatin was escalated (by AUC0.5 increments) starting from AUC3 and AUC4 respectively. Amifostine (600 mg/m2) was administered i.v. before carboplatin and GM-CSF (480 microg) was injected s.c. on days 5, 6 and 10, 11 of each cycle. Six cycles were given and response was assessed 2 weeks after the end of chemotherapy. None out of four patients treated in the 6th dose level cohort (50 mg/m2 of docetaxel and AUC4 of carboplatin every 2 weeks) showed any grade 2-4 hematologic toxicity. Mild non-hematologic toxicity such as neuropathy, leg edema, pleural effusion, pyrexia, alopecia grade 2 and hypersensitivity was observed in 4-12% of patients. Out of four patients treated in a 7th cohort (docetaxel 60 mg/m2 and carboplatin AUC4), one developed grade IV neutropenia and two developed grade 3 severe asthenia requiring treatment delay for 2 weeks. Out of 11 patients with PR following docetaxel radio-chemotherapy, 7 (63%) showed CR after docetaxel/carboplatin additional chemotherapy. Eight out of 17 patients with MR following docetaxel radio-chemotherapy showed PR (47%) and one showed CR (6%) after additional chemotherapy. High dose combined docetaxel (50 mg/m2) and carboplatin (AUC4) chemotherapy can be safely administered on a two-weekly basis if supported with amifostine and GM-CSF. Such an additional therapy may be important in patients with incomplete response after chemo-RT. Broad spectrum cytoprotection with amifostine and GM-CSF may also contribute to the reduction of incidence of neurosensory reactions and asthenia in patients treated with taxanes.

Adult↗
PubMed1996

[Anxiolysis, sedation, and stress reduction following oral premedication with midazolam in adults. A comparison with dipotassium clorazepate and placebo].

Benzodiazepines are the most commonly used anxiolytic agents. Among the benzodiazepines, midazolam has the advantage of a short elimination half-life, which is especially useful in outpatient surgery. However, in contrast to other commonly prescribed benzodiazepines, such as chlorazepate dipotassium, oral premedication with midazolam has not been thoroughly investigated. Therefore, the present study was performed to compare anxiolysis, sedation and stress reduction with midazolam and clorazepate dipotassium in adults. METHODS. After IRB approval and informed consent had been obtained, 85 patients scheduled for breast biopsy were studied. The patients were chosen at random to receive either 7.5 mg midazolam (n = 29), 20 mg clorazepate dipotassium (n = 28) or placebo (n = 28) preoperatively. Before premedication, immediately prior to surgery and postoperatively in the recovery room, the following parameters were determined with visual analogue scales (VAS): "asthenia," "depression," oral salivation, muscle tension, motoric restlessness and sweating of the palms. In addition, anxiety (STAI-G-X-1, Spielberger), heart rate and arterial blood pressure were measured. Before patients underwent surgery, the degree of sedation was evaluated by the anaesthesiologist. RESULTS. Clorazepate dipotassium and midazolam both caused a reduction in anxiety as compared with the placebo (P < 0.05). Only clorazepate dipotassium reduced anxiety postoperatively (P < 0.05). Neither midazolam nor clorazepate dipotassium caused a reduction in "asthenia" and "depression." Midazolam was more effective in preventing increased blood pressure than clorazepate dipotassium and the placebo (P < 0.05). Furthermore, after premedication with midazolam, salivation, muscle tension, motoric restlessness and sweating of the palms remained stable, in contrast to the results after premedication using clorazepate dipotassium or placebo (P < 0.05). CONCLUSIONS. The anxiolytic effects of 7.5 mg midazolam and 20 mg clorazepate dipotassium were similar after oral application. However, the anxiolytic effect of midazolam is shorter-lived than that of clorazepate dipotassium. In contrast to clorazepate dipotassium, midazolam produced no increase in arterial blood pressure and stabilized oral salivation, production in the palms, muscle tension and motoric restlessness.

Adult↗
PubMed1999

A phase II trial of CI-958 in patients with hormone-refractory prostate cancer.

PURPOSE: To assess the antitumor activity of the benzothiopyranoindazole CI-958 ¿5-[(2-aminomethyl)amino]-2-[2-(diethylamino)ethyl]-2H- [l]benzothiopyrano[4,3,2-cd]-indazol-8-ol trihydrochloride¿ in hormone-resistant prostate carcinoma, using an intravenous dose of 700 mg/m(2) every 3 weeks. PATIENTS AND METHODS: Patients eligible for this study had advanced prostate carcinoma that had failed hormonal treatment. Changes in an initially elevated prostate-specific antigen (PSA) level and regression of objectively measurable disease were used as response criteria. RESULTS: All 33 patients enrolled were evaluated. Of 30 with elevated PSA levels, 6 had a >50% decline maintained for >30 days; response durations ranged from 105 to 623 days. Eleven patients had objectively measurable disease; two had partial responses (lasting 316 and 461 days) consisting of shrinkage of retroperitoneal nodes and of masses surrounding the rectum and bladder. The survival of all responding patients ranged from 366 days to 709 days and the median survival of all patients was 12 months (range 1-23 + months). Neutropenia was common, but thrombocytopenia was not. Nonhematologic side effects included nausea, vomiting, anorexia, asthenia, and chills, but were usually mild. The drug caused phlebitis when given into peripheral veins and central venous administration is recommended. No consistent reductions in cardiac function were documented by sequential assessment of left ventricular ejection fractions. CONCLUSIONS: CI-958 has modest but definite antitumor activity in hormone-resistant prostate carcinoma. Its toxicities include neutropenia, nausea, vomiting, anorexia, asthenia, chills and phlebitis.

Adult↗
PubMed2005

The Supportive Care Task Force at the University of L'Aquila: 2-years experience.

The Supportive Care Task Force (SCTF) was established within the Medical Oncology Department at the University of L'Aquila in May 2002. The missions of the SCTF were to allow systematic evaluation and treatment of symptoms, to warrant continuity of care in all phases of disease and to provide medical oncology residents with training in the treatment of symptoms. A medical oncologist, two senior residents in medical oncology and a registered nurse comprised the SCTF. A psychiatrist, two neurologists, a dietician, and two physiotherapists served as consultants or on a part-time basis. Four beds in two-bedded rooms inside the Medical Oncology Department were reserved to SCTF. A close integration with the physicians of the Medical Oncology Department was realised. The only criterion to admission was the presence of uncontrolled symptoms. Patients were evaluated and monitored with the visual analogue scale for pain and with the Edmonton Symptom Assessment Scale (ESAS). The Palliative Prognostic Score (PaP Score) was employed to assess the prognosis. Non-clinical needs were evaluated with the Need Evaluation Questionnaire (NEQ). Protocols for the treatment of common symptoms were available in written form for consultation by physicians, residents and nurses. From 1 May 2002 to 31 May 2004, we observed 208 patients: 111 women and 97 men. The median age was 64.7 (range 28-90) years. Fifty-four patients (25.9%) were admitted more than once, for a total of 285 admissions. One hundred ninety-nine admissions (69.5%) were for supportive care while 86 admissions (30.5%) were for supportive care and active treatment. The most frequent symptoms were asthenia and anorexia. We registered excellent results regarding the treatment of pain, nausea and dyspnea while psychological symptoms, anorexia and asthenia proved more difficult to treat. Two hundred twenty patients were discharged: 142 (49.8%) home; 76 (26.7%) to the Home Care Service and two (0.7%) to others units of the hospital. Sixty-five (22.8%) died in our unit.

Adult↗
PubMed1999

Management of dyspnea in advanced cancer patients.

Dyspnea is a frequent and devastating symptom among advanced cancer patients and is often difficult to control. However, there has been considerably less emphasis in the literature on the appropriate characterization and management of this symptom than of other cancer-related symptoms. The purpose of this paper is to review issues relating to the prevalence, causes, prognosis and treatment of dyspnea in patients with advanced cancer. A Medline search of the literature published from 1966 to February 1999 was conducted. Dyspnea occurs in 21-78.6% of advanced cancer patients and is reported to be from moderate to severe in 10-63% of the patients. The frequency and severity of dyspnea increase with the progression of the disease and/ or when death is approaching. Lung cancer patients with dyspnea have shorter survival than patients with other types of cancer. Dyspnea can be a direct effect of the cancer, an effect of therapy or not related to the cancer or therapy. In addition to cancer, patients may suffer from chronic obstructive pulmonary disease, congestive heart failure, nonmalignant pleural effusion, pneumonitis, air flow obstruction, or bronchospasm associated with asthma. In the absence of lung or heart disease, dyspnea may be a clinical expression of the syndrome of overwhelming cachexia and asthenia or of severe asthenia. Many different causes may co-exist in a patient. Whenever possible, an attempt should be made to treat underlying cancer. Radiotherapy and chemotherapy may relieve dyspnea also in patients who fail to achieve a major objective response. Symptomatic measures in addition to specific treatments for the underlying cancer and/or other pulmonary and cardiovascular diseases are indicated. Oxygen therapy has proved effective in hypoxemic and nonhypoxemic patients. The role of transfusion therapy to relieve anemia-related dyspnea in advanced and terminal cancer patients is still controversial. Oral, subcutaneous and intravenous opioids are effective but underused in these patients, whereas currently available evidence does not support the clinical use of nebulized opioids. While benzodiazepines are frequently used in patients with dyspnea, these drugs were ineffective in four out of five randomized controlled trials. Other components of the symptom expression are better managed by supportive counseling, occupational therapy or physiotherapy. While the mechanism of breathing and the consequences of different pathologic conditions for both respiratory function and gas exchange are well known, the genesis and pathophysiology of dyspnea as a symptom are much less well understood. Palliative care assessment should be focused on dyspnea as a symptom rather than on the functional and gas exchange abnormalities. Increased research on the appropriate management of dyspnea is needed.

Dyspnea↗
PubMed2002

Supportive and palliative care: experience at the Institut Jules Bordet.

The Supportive and Palliative Care Unit of the Institut Jules Bordet officially started its activities in February 1999. Our Unit comprises eight beds (four rooms with one bed each and two rooms with two beds each). We admit advanced cancer patients presenting with severe symptoms whose control is going to require all the expertise of a multidisciplinary team. Whilst these eight beds are identified geographically in the hospital, the team's mobility assures continuity of care for patients who wish to stay in another department. The infrastructure of the Unit and its rooms allow close family members who wish to sleep close to the patients to do so. Otherwise, visits are allowed round the clock, though always with due consideration for patients' comfort. Patients are referred either by a physician working in our Institution (medical oncologist, surgeon, or radiotherapist) or by their family physicians. Less frequently, patients themselves specifically ask to be admitted to our Unit. The activity of the Unit itself during its first year of functioning can be summarized as follows. We admitted 155 advanced cancer patients, for a total number of 210 hospitalizations. Patients were admitted a median of 35 months after their diagnosis and a median of 20 days before death. Stays were generally short (median 11 days). We systematically used quantitative assessment tools (MMSQ, MDAS,EFAT and various VAS) to detect and monitor their symptoms and any complications. The main symptoms on admission were pain, anorexia, asthenia, dyspnea and anxiety/depression. Pain, nausea/vomiting, constipation and cough were controlled in almost all patients, whereas control of asthenia and anorexia was most often insufficient. In 51% of our cases the patients could be discharged home; 40% died in the unit; 4% were transferred to long-term palliative care units and 1% to other units within our Institution (4% were still hospitalized at the time of this analysis).

Adult↗
PubMed2001

Is there a role for melatonin in supportive care?

Melatonin (MLT) is the main hormone released from the pineal gland and has proved to have physiological antitumor activity. MLT has been shown to exert anticancer activity through several biological mechanisms: antiproliferative action, stimulation of anticancer immunity, modulation of oncogene expression, and anti-inflammatory, anti-oxidant and anti-angiogenic effects. Several experimental studies have shown that MLT may inhibit cancer cell growth, and preliminary clinical studies seem to confirm its anticancer property in humans. In addition, MLT may have other biological effects, which could be useful in the palliative therapy of cancer, namely anticachectic, anti-asthenic and thrombopoietic activities. On this basis, the present clinical investigation was performed in an attempt at better definition of the therapeutic properties of MLT in human neoplasms. In a first clinical study, we evaluated the effects of MLT in a group of 1,440 patients with untreatable advanced solid tumors, who received supportive care alone or supportive care plus MLT. In a second study, we evaluated the influence of MLT on the efficacy and toxicity of chemotherapy in a group of 200 metastatic patients with chemotherapy-resistant tumor histotype, who were randomized to receive chemotherapy alone or chemotherapy plus MLT. In both studies, MLT was given orally at 20 mg/day during the dark period of the day. The frequency of cachexia, asthenia, thrombocytopenia and lymphocytopenia was significantly lower in patients treated with MLT than in those who received supportive care alone. Moreover, the percentage of patients with disease stabilization and the percentage 1-year survival were both significantly higher in patients concomitantly treated with MLT than in those treated with supportive care alone. The objective tumor response rate was significantly higher in patients treated with chemotherapy plus MLT than in those treated with chemotherapy alone. Moreover, MLT induced a significant decline in the frequency of chemotherapy-induced asthenia, thrombocytopenia, stomatitis, cardiotoxicity and neurotoxicity. These clinical results demonstrate that the pineal hormone MLT may be successfully administered in medical oncology in the supportive care of untreatable advanced cancer patients and for the prevention of chemotherapy-induced toxicity.

Adjuvants, Immunologic↗
PubMed1993

Long-term effects of theophylline in atrial fibrillation with a slow ventricular response.

In 17 patients (aged 78 +/- 9 years) with symptomatic atrial fibrillation and a slow ventricular response not related to drugs, a resting electrocardiogram and 24-hour Holter recording were obtained before and 5 to 6 days after administration of slow-release theophylline (700 mg/day), and successively every 3 months during the long-term phase. Fourteen patients had organic heart disease, and 13 complained of syncope or presyncope, and 4 of asthenia and easy fatigability. At the steady-state evaluation, theophylline significantly increased resting heart rate (HR) by 42%, mean 24-hour HR by 31% and minimal 24-hour HR by 34%. Cardiac pauses > 2,500 ms disappeared or markedly decreased. The daily number of wide QRS complexes increased. Serum theophylline level was 13 +/- 5 ng/ml. During the follow-up period (20 +/- 18 months), the mean daily theophylline dosage was 450 mg and the mean serum theophylline level 9 ng/ml. Seven patients died: 1 because of heart failure, and 6 because of noncardiac death. One patient complained of a syncopal episode during 1 visit. The drug markedly reduced asthenia and easy fatigability. During the long-term phase, HR increased spontaneously in 3 patients, and the treatment was interrupted. In 2 patients, theophylline had to be discontinued because of gastric intolerance. During long-term therapy, HR was similar to that observed at the steady-state evaluation, despite the reduction in daily dosage. The data suggest that theophylline is an effective therapy in most patients with symptomatic atrial fibrillation and a slow ventricular response.

Aged↗
PubMed1991

Comparison of the new alpha 1-blocker alfuzosin with propranolol as first-line therapy in hypertension.

The new alpha 1-blocker alfuzosin was compared with propranolol as monotherapy for hypertension in a double-blind, parallel group study of 8-week duration in 40 patients with essential hypertension. The patients (11 males, 29 females; mean age 47.8 +/- 2.2 years in the alfuzosin group and 46.6 +/- 2.4 years in the propranolol group) randomly received either alfuzosin from 2.5 mg b.i.d. up to 10 mg b.i.d. or propranolol from 40 mg b.i.d. up to 160 mg b.i.d. according to an individualized dose-titration schedule. The two groups were comparable with respect to disease history, cardiovascular risk factors, concomitant diseases, previous treatments and end-placebo blood pressure and heart rate values. Four patients did not complete the study, two patients in the alfuzosin group: one patient because of postural hypotension and the second one because of breast cancer; and two patients in the propranolol group: one patient for inefficacy and the second one lost to follow-up. At the end of the 8-week trial the mean daily doses were 12.2 +/- 0.61 mg and 196 +/- 9.82 mg for alfuzosin and propranolol, respectively. The antihypertensive effects of the two drugs were comparable. Upright and supine blood pressures decreased significantly with both treatments from the second week on (P less than 0.001 for all BP values). At the end of the 8-week double-blind trial, 83% of alfuzosin patients and 67% of propranolol patients were normalized. The two treatments differed significantly with respect to their effect on heart rate. Alfuzosin did not induce marked changes in heart rate: only a slight increase was observed. In contrast, propranolol caused bradycardia, more marked in the upright position. Palpitations, headache, asthenia and orthostatic hypotension were reported in the alfuzosin group. Asthenia and decreased libido were reported in the propranolol group. These data prove that alfuzosin has antihypertensive effects equivalent to propranolol and it is an interesting agent for the therapy of essential hypertension. It can be used as a first agent at doses between 5 and 20 mg/day with satisfactory therapeutic response and without relevant side-effects.

Adrenergic alpha-Antagonists↗
PubMed2006

Perceptual voice analysis of patients with subglottic stenosis.

OBJECTIVES: To characterize the perceptual assessment of vocal quality in subglottic stenosis (SGS) patients and to identify risk factors for dysphonia. STUDY DESIGN AND SETTING: Retrospective review, academic center. METHODS: Perceptual voice assessment using GRBAS scale (Grade, Roughness, Breathiness, Asthenia, Strain); patient characteristics determined for 31 SGS cases. RESULTS: The mean GRBAS (0 to 3 scale, 0 = normal quality) for SGS patients at their initial visit was G(1.4)R(1.2)B(0.5)A(0.5)S(1.1). For males vs females: G(2.1 vs 1.1)R(2.0 vs 0.8)B(1.0 vs 0.4)A(1.0 vs 0.3)S(1.7 vs 0.9). The Grade (P < 0.03), Breathiness (P < 0.04), and Asthenia (P < 0.02) assessments were significantly more dysphonic in patients with multilevel stenosis; vocal fold motion impairment (VFMI) also impacted overall Grade (P < 0.01). Overall Grade (P < 0.002), Roughness (P < 0.007), and Breathiness (P < 0.006) were significantly worse in patients with prior airway surgery. CONCLUSION: SGS patients demonstrate a mild to moderate change in perceptual voice characteristics with males in this series being more affected than females. Negative risk factors include multiple stenoses, VFMI, and previous airway surgery. SIGNIFICANCE: This is the first systematic report of perceptual voice assessment in subglottic stenosis. SGS patients have notable degrees of dysphonia with identifiable risk factors.

Auditory Perception↗
PubMed2004

[Hydroxyurea treatment for unresectable meningioma].

BACKGROUND: Management of unresectable progressive meningioma remains controversial and constitutes a major challenge since therapeutic options including chemotherapy and hormone modulation are limited. Recent data have suggested that hydroxyurea treatment may have an antitumoral effect. The purpose of this prospective phase II study was to evaluate the efficacy of hydroxyurea treatment for unresectable progressive meningioma. METHODS: From 1997 to 1999, consecutive patients presenting unresectable meningioma with clinically and/or neuroradiologically documented progression were considered for entry into this protocol. Previous radiotherapy was not a mandatory inclusion criteria. Treatment consisted of continuous oral administration of hydroxyurea at a dose of 20 mg/kg per day. Follow-up assessment included physical examination, computed tomography (CT), and magnetic resonance imaging (MRI) performed every three months, as well as regular blood testing. The primary endpoint was documentation of objective response by MRI or CT. RESULTS: The intent-to-treat population was 43 patients with at least 18 months follow-up. Median age was 60.4 years. Twenty-eight patients had undergone surgery following initial diagnosis. The meningioma was located in the skull base in 67% of patients. Histology was benign in 18 and atypical in 10. The eligible population included 36 patients with documented progressive disease at the time of inclusion; with progression documented clinically in 29 (67.5%) and/or radiologically in 20 (46%). In 7 patients, clinical or radiological progression could not be confirmed. The intent-to-treat analysis at median 26 months follow-up revealed objective response to hydroxyurea in only 3 patients (7%) including one on the basis of improvement in visual symptoms and two on MRI analysis. Progressive disease was observed clinically or radiologically in 26 patients (60.5%). Of the eligible population (n=36), 2 achieved an objective response and 13 (36%) exhibited stabilization under hydroxyurea therapy, while 21 (58%) progressed under treatment. Overall tolerance was good but anemia (grade I-II) and asthenia (grade I-II) were observed in 28% and 23.5% respectively. Treatment was discontinued in 3 patients because of chronic skin toxicity in one and anemia and asthenia in two. CONCLUSION: Hydroxyurea treatment is of marginal efficacy for meningioma and must not be considered as an alternative if radiotherapy or surgery is feasible. New efficient medical treatments are still required for progressive meningiomas.

Adult↗
PubMed2005

[Thalidomide in the treatment of chronic discoid lupus erythematosus].

INTRODUCTION: Thalidomide is the second line treatment of chronic lupus erythematosus. The efficacy of this treatment, the minimal effective doses and tolerance are poorly documented in the literature. PATIENTS AND METHODS: We present the data of a single-center retrospective studied among 18 patients with chronic lupus erythematosus, treated with thalidomide from 1998 to 2003. Inclusion criteria were: the presence of clinical lesions evoking the disease, confirmed by histological examination and direct immunofluorescence and treatment with thalidomide for more than 2 months. RESULTS: Mean age on diagnosis was of 35.8 years. Thalidomide had been initiated a mean of 10.6 years after diagnosis of chronic lupus erythematosus. In 13 out of 18 patients, thalidomide had been prescribed because of failure with prior treatments. Fifteen patients were improved by thalidomide (83.3 p. 100), with 11 (61 p. 100) complete and 4 (22 p. 100) partial remissions. Two (11 p. 100) patients were stabilized and treatment failed in one. The mean initial dose was of 100 mg/d (50-150), and maintenance dose was of around 50 mg/d (56 mg/d). The mean follow-up with thalidomide was of 19.4 months. Only one withdrawal due to side effects was reported. The most frequent side effects were: asthenia (33 p. 100), paresthesia (22 p. 100) and weight gain (16.6 p. 100). No side effects were reported in 10 out of 18 patients. DISCUSSION: This study confirms the efficacy of low dose thalidomide in the treatment of chronic lupus erythematosus. In our experience, tolerance to this treatment is good, the most frequent side effect was asthenia, but usually mild. No significant peripheral neuropathy was noted. The fear of side effects, notably neurological, should not delay initiation of thalidomide in the case of failure with current treatments.

Adolescent↗
PubMed1994

Glucocerebrosidase for treatment of Gaucher's disease: first German long-term results.

Until recently, there was no specific therapy available for patients with Gaucher's disease. Since April 1991 a highly purified human placental preparation of glucocerebrosidase (Ceredase, Genzyme) has been available for clinical studies in Germany. Sequential deglycosylation of the native enzyme yields a mannose-terminated preparation that may preferentially bind to the plasma membrane of macrophages. The present report analyzes the first German (and European) long-term results with glucocerebrosidase therapy in five patients with type I Gaucher's disease (four women and one man, aged 29-40 years). All patients suffered from excessive enlargement of the liver and spleen with subsequent pancytopenia and from skeletal complications. Multiple pathological fractures had already occurred in three of the five patients, requiring several surgical procedures. Fatigue and asthenia were present in all patients. The initial dose of glucocerebrosidase was chosen according to the severity of complications in the individual patient (20-50 U/kg given i.v. every 2nd week) and was performed in the five patients for 12-18 months. After a few weeks all patients reported that fatigue and asthenia were markedly reduced. After 12 months, blood counts of erythrocytes, leukocytes and platelets had completely normalized in all but one of the patients. After 4-6 months a significant reduction in the sizes of liver and spleen could be observed in all patients. No further fractures occurred during treatment. Significant side-effects of glucocerebrosidase treatment did not occur. The new glucocerebrosidase preparation offers the first effective drug therapy for patients with Gaucher's disease. Although the treatment proved effective and harmless, it is, at least initially, very expensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed2002

Phase I dose-escalating study of raltitrexed ('Tomudex') and cisplatin in metastatic non-small cell lung cancer.

BACKGROUND: The aim of this Phase I, dose-escalation study was to determine the maximum tolerated dose (MTD), recommended dose (RD), and dose-limiting toxicity (DLT) of a raltitrexed ('Tomudex') and cisplatin combination in patients with previously untreated, metastatic non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: Patients received raltitrexed (15-min intravenous infusion), followed by cisplatin (1-h intravenous infusion), every 3 weeks at escalating dose levels. RESULTS: In total, 21 patients entered the study. No DLT was observed up to dose level 4 (raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2)), or in the first 3 patients who received dose level 5 (raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2)). However, 1 patient, entered at dose level 6 (raltitrexed 4.0 mg/m(2) plus cisplatin 80 mg/m(2)) experienced severe toxicity (including grade 3 diarrhea), and no further patients were recruited at this level. Of 4 additional patients who received raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), 3 also experienced DLTs. The most common adverse events included nausea/vomiting, asthenia, diarrhea, and hematologic toxicities. Of 19 patients evaluated for response, 3 achieved a partial response, 13 had stable disease, and 3 progressed. CONCLUSIONS: The MTD is raltitrexed 3.5 mg/m(2) plus cisplatin 80 mg/m(2), and the RD for future studies is raltitrexed 3.0 mg/m(2) plus cisplatin 80 mg/m(2); DLTs were diarrhea and asthenia. The combination of raltitrexed and cisplatin shows clinical activity in patients with metastatic NSCLC.

Aged↗
PubMed1993

[Chronic fatigue syndrome: a critical review].

The term "chronic fatigue syndrome" (CFS) applies to a condition of unknown aetiology characterized clinically by an association of subjective symptoms, the most constant being an invalidating tiredness. The diagnostic criteria in current use do not permit to isolate an homogeneous subgroup among patients consulting for chronic asthenia. In the present state of research no infectious or immunological cause has been demonstrated conclusively, although a persistent enterovirus or herpesvirus type 6 infection or a state of chronic immune activation seem to play a role in some cases. Patients who fulfill the criteria of CFS present with psychiatric overmorbidity, essentially depressive, and in 50% of the cases with the mental disorders preceding CFS. The various theoretical models linking CFS to psychopathology are discussed, and finally the syndrome is regarded as a social construction reproducing or renovating the neurasthenia of the late 19th century. There is no specific treatment of CFS, but antidepressants, cognitive-behavioural therapy and perhaps certain immuno-modulators can be useful. The future lines of research should endeavour to isolate a subgroup of patients with prolonged asthenia after a recognized episode of infection and to identify the immunological, psychological and behavioral characteristics of this particular group as well as their reciprocal interactions.

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