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PubMed2006

UFT in combination with oxaliplatin: clinical phase I study in patients with advanced or metastatic solid tumors.

This phase I trial evaluated the combination of oxaliplatin plus UFT in patients with advanced solid tumors to determine the maximum tolerated dose (MTD) and the dose limiting-toxicity for future phase II trials. Eligible patients (N = 27) were treated in sequential cohorts of three to six patients. The starting doses for oxaliplatin and UFT were 70 mg/m2 and 250 mg/m2/day respectively, and five dose levels were designed up to 85 mg/m2 and 400 mg/m2/day. Oxaliplatin was administered i.v. on day 1 and 15, and oral UFT was given daily in three divided doses on days 1-21 followed by 1 week rest of a 28-day cycle. At the recommended dose, six additional patients were entered. In total, 79 courses were administered with a median of 3 (range 1-6). MTD was not reached; oxaliplatin 85 mg/m2 on day 1 and 15 plus UFT 400 mg/m2/day for 21 days was considered the optimum combination for phase II trials. Gastrointestinal toxicity and asthenia were the most common adverse events. Eight out of 13 patients (61.5%) with metastatic colorectal cancer achieved stable disease. UFT plus oxaliplatin is a feasible and safe combination. A phase II trial in first-line advanced colorectal cancer is ongoing.

Administration, Oral↗
PubMed2005

Irofulven demonstrates clinical activity against metastatic hormone-refractory prostate cancer in a phase 2 single-agent trial.

BACKGROUND: The primary objective of this study was to assess the antitumor activity of irofulven in patients with hormone-refractory prostate cancer by measuring a sustained decrease of 50% or greater in serum prostate-specific antigen (PSA) levels. PATIENTS AND METHODS: Forty-two patients (median age, 73 years) received at least 1 dose of 10.6 mg/m2 irofulven per day on days 1-5 of a 28-day course. Eligible patients had pathologically confirmed metastatic hormone-refractory adenocarcinoma of the prostate and had not received prior cytotoxic chemotherapy. RESULTS: Forty-two patients received a median of 3 courses of irofulven. Thirty-two patients received at least 2 courses of therapy and were evaluable for efficacy. Four patients (13%) achieved partial response, with a median duration of 2.9 months (range, 2.6-5.8 months). Twenty-seven patients (84%) had disease stabilization and 1 patient (3%) progressed on study. Median progression-free survival was 3.2 months (95% confidence interval, 2.3-4.2 months), with a median progression-free survival of 4.2 months (range, 3.5-6.9 months) for responders. Grade 4 toxicities consisted of thrombocytopenia, anemia, and neutropenia, occurring in 1 patient each. The most common treatment-related grade 3 nonhematologic toxicities included asthenia (19% of patients), vomiting (14%), nausea (12%), and infection without grade 3/4 neutropenia (10%). CONCLUSION: Irofulven shows activity in hormone-refractory prostate cancer and has an acceptable safety profile, warranting further investigation of this drug, particularly in combination therapies.

Adenocarcinoma↗
PubMed2005

A phase II study of gemcitabine in patients with relapsed or refractory low-grade non-Hodgkin lymphoma.

PURPOSE: The purpose of this study was to determine the tolerability, clinical response rate, and time to disease progression of gemcitabine treatment in patients with low-grade non-Hodgkin lymphoma. (NHL) PATIENTS AND METHODS: Twenty patients with low-grade NHL and progression of disease after at least 1 prior treatment regimen were prospectively enrolled. The treatment regimen consisted of 1200 mg/m2 gemcitabine intravenously administered weekly for 7 weeks followed by a 1-week rest. Subsequent treatment was given weekly for 3 weeks followed by a 1-week rest and repeated for a maximal treatment of 6 cycles until disease progression or unacceptable toxicity. RESULTS: The predominant histologic subtypes among our patients were small lymphocytic (8 of 20) and follicular (7 of 20). Grade III/IV hematologic toxicity was observed in 15 of 20 patients and dose reductions or treatment delays occurred in 19 of 20 patients. Fatigue and asthenia were treatment-limiting in many patients. There were no complete or partial responses observed and only 2 patients had stable disease after 12 weeks of treatment. The average time to progression or off-study status was 2.3 months (95% confidence interval, 1.7-2.9) with 8 patients showing progression of disease. Twelve patients were taken off the study as a result of unacceptable toxicity before observed progression of disease. No patient completed the planned course of therapy. With a median follow up of 10.2 months, 10 of 20 patients remained alive. CONCLUSION: Gemcitabine as a single agent, in this dosage and schedule, has minimal clinical activity in relapsed or refractory low-grade lymphomas and was associated with considerable toxicity. Therefore, further study of gemcitabine in this setting is not justified.

Aged↗
PubMed2005

Biweekly administration of cisplatin/gemcitabine in advanced nonsmall cell lung cancer.

INTRODUCTION: In an attempt to increase the dose intensity of cisplatin and gemcitabine given to patients with stage IIIB or IV nonsmall cell lung cancer without increasing toxicity, we have studied a biweekly administration schedule. We analyze the safety and efficacy of this treatment. METHODS AND PATIENTS: In this study, cycles of 50 mg/m2 cisplatin with 2500 mg/m2 gemcitabine were given on days 1 and 15 every 28 days. The median age of the 49 patients was 62 years and 23 were in stage IIIB patients (46.9%), whereas 26 (53.1%) were in stage IV. RESULTS: Overall response rate was 38.8%, 52.2% for stage IIIB and 26.9% for stage IV. Median survival was 48 weeks and 1-year survival was 44%, with 66.7% of stage IIIB patients and 13.3% of stage IV patients surviving for 1 year. In the study, 178 cycles were administered, a mean of 4 cycles per patient. The intensity of the 359 administrations reached 91.16% of the planned dosage, although 49 were delayed for 1 week while subjects recovered from the toxicity. There was 1 toxic death and 2 patients experienced vascular toxicity with distal arterial ischemic severe changes in their lower extremities. There were 7 episodes of grade 2 neutropenia, 2 of grade 3, and one of grade 4; however, no cases of febrile neutropenia were seen. The predominant nonhematologic toxic effects were asthenia and nausea/vomiting. CONCLUSION: The schedule of cisplatin and gemcitabine analyzed is active with a good therapeutic index.

Adult↗
PubMed2005

Dose-finding and phase 2 study of weekly paclitaxel (taxol) and cisplatin combination in treating Chinese patients with advanced nonsmall cell lung cancer.

OBJECTIVES: The aim of the present study is to evaluate the efficacy and toxicity of weekly paclitaxel combined with cisplatin as first-line chemotherapy in patients with locally advanced or metastatic nonsmall cell lung cancer (NSCLC) and to identify the optimal dose of weekly paclitaxel to be administered safely and effectively. METHODS: Chemonaive patients with NSCLC, stage 3B with malignant pleural effusion, or stage 4 were enrolled in this study. In the dose-finding study, patients took paclitaxel once weekly at an initial dose of 50 mg/m2 and 3 weeks followed by cisplatin on day 15 at a fixed dose of 80 mg/m2. The escalating dose for paclitaxel was 10mg/m2 for each level. In the phase 2 study, patients received paclitaxel at maximum tolerated dose (MTD). RESULTS: The MTD for paclitaxel was 60 mg/m2. Of the 47 eligible patients, 7 patients had a complete response and 15 achieved a partial response. The overall response was 46.8% (95% CI, 32.0% to 61.6%). The median survival was 16 months (95% CI, 13.4 to 18.6 months). Twenty-four patients (51.1%) completed 6 cycles of treatment. With regard to hematological toxicity, although grade 3/4 neutropenia was observed in 5 patients (10.6%), there was no febrile neutropenia. The major nonhematological toxicity was asthenia, which was observed in all patients (17 patients grade 1/2 and 30 patients with grade 3/4). CONCLUSIONS: Weekly paclitaxel combined with cisplatin on day 15 is a safe and effective regimen as a first-line chemotherapy in NSCLC. The MTD for this regimen was 60 mg/m.

Adult↗
PubMed2006

Irinotecan, oxaliplatin plus bolus 5-fluorouracil and low dose folinic acid every 2 weeks: a feasibility study in metastatic colorectal cancer patients.

OBJECTIVES: Irinotecan or oxaliplatin combined with 5-fluorouracil (5-FU) +/- folinic acid (FA) has changed the treatment standards for metastatic colorectal cancer (CRC). The oxaliplatin and irinotecan combination has reported consistent activity. The purpose of this phase II study was to assess the efficacy and safety of the simultaneous administration of a triple chemotherapy combination of oxaliplatin, irinotecan, 5-FU bolus, and FA. MATERIALS AND METHODS: Eligible patients had metastatic CRC with no prior oxaliplatin or irinotecan-based chemotherapy. Treatment consisted of oxaliplatin 85 mg/m2 followed by irinotecan 150 mg/m2, repeated every 15 days, with 5-FU 500 mg/m2 bolus and FA 20 mg/m2 on days 1, 8, and 15. An early amendment suppressed the day 8 5-FU/FA. RESULTS: Twenty-six eligible treated patients receiving 253 doses were assessed for toxicity. Myelosuppression was the most frequent toxicity; grade 3 to 4 neutropenia and febrile neutropenia occurred in 50% and 15% of patients, respectively. The treatment schedule modification, omitting the 5-FU dosing on day 8, considerably improved treatment compliance, reducing the incidence of febrile neutropenia, diarrhea, and asthenia. Among the 25 patients evaluable for efficacy, 10 had objective responses including 1 complete response (CR) (4%) and 9 partial responses (PR) (36%), giving an overall response rate of 40%. Median time to progression was 6.20 months [95% confidence interval (CI), 5.44-6.96]. Median overall survival was 12.95 months. CONCLUSIONS: The administration of a triple combination produced promising objective responses with acceptable toxicity but does not seem to produce an evident benefit in time-related parameters.

Adult↗
PubMed2006

Subcutaneous interleukin-2 and interferon-alpha in metastatic renal cell carcinoma: results of a French regional experience in Languedoc.

OBJECTIVES: To assess the efficacy and toxicity of an immunotherapy regimen combining subcutaneous (SC) interleukin-2 (IL-2) and interferon-alpha (IFN) in patients with metastatic renal cell carcinoma (MRCC). METHODS: The present study included 86 patients with MRCC. Data on treatment toxicity and efficacy (responses rates and overall survival) were collected on a hospital database. Treatment consisted of 6-week cycles repeated every 2 months for a maximum of 3 cycles. Each cycle included SC IL-2 20 x 10 MIU/m2 3 times/wk on weeks 1 and 4; 5 x 10 MIU/m2 3 times/wk on weeks 2, 3, 5, and 6, in combination with IFN 6 x 10 MIU/m2 once weekly on weeks 1 and 4; and 3 times/wk on weeks 2, 3, 5, and 6. RESULTS: Seventy (82%) and 71 (83%) patients received more than 80% of the planned doses of IL-2 and IFN during the first cycle, respectively. Ten patients had to stop therapy before the end of the first cycle because of excessive toxicity (7 patients) or rapidly progressive disease (3 patients). Only 17 (28%) proceeded to the second cycle. Main toxicities included fever and asthenia in 86 (100%) patients, nausea/emesis in 83 (96%) patients, skin disorders in 69 (80%) patients, hypotension in 56 (65%) patients, and diarrhea in 50 (58%) patients. Sixty-seven (78%) patients developed at least one episode of grade 3 toxicity. Objective responses were observed in 13 patients, including 4 complete and 9 partial responses (15%; 95% confidence interval, 9.5-20.5%). After a median follow-up of 45 months, the median time to progression was 4 months (range, 1-41) and the median survival was 14 months (range, 1-89). CONCLUSIONS: Only a small subset of patients with MRCC is likely to benefit from treatment with IL-2 and IFN. As toxicity is significant, the refinement of predictive variables for sensitivity to immunotherapy is mandatory.

Adult↗
PubMed2004

Quetiapine versus placebo in combination with lithium or divalproex for the treatment of bipolar mania.

Quetiapine (QTP) combined with lithium (Li) or divalproex (DVP) for the treatment of mania was evaluated in 2 double-blind, placebo-controlled studies. Patients were randomized to 3 or 6 weeks of treatment with QTP plus Li/DVP or placebo (PBO) plus Li/DVP. Quetiapine was dosed up to 800 mg/d; Li was dosed to achieve serum concentrations of 0.7-1.0 mEq/L and DVP to 50-100 microg/mL. A total of 402 patients were randomized: 197 to QTP + Li/DVP and 205 to PBO + Li/DVP. The mean quetiapine dose in responders was 492 (+/-204) mg/d. Improvement in the Young Mania Rating Scale (YMRS) at day 21 in the QTP + Li/DVP group (-15.29) was statistically superior to the PBO + Li/DVP group (-12.19) (P < 0.05). A statistically significant difference in favor of quetiapine was observed within the first week (P < 0.05). Significantly more QTP + Li/DVP patients achieved a response (> or =50% decrease in the YMRS) at day 21 (QTP + Li/DVP, 55.7%; PBO + Li/DVP, 41.6%;P < 0.01). Improvements in Clinical Global Impression-Bipolar Severity of Illness scores by day 21 were also significantly greater in QTP + Li/DVP-treated patients (-1.59) versus PBO + Li/DVP (-1.19) (P < 0.01). Common adverse events (> or =5% and twice that in the PBO + Li/DVP group) in the QTP + Li/DVP group were somnolence, dry mouth, and asthenia. Quetiapine combined with Li/DVP was not associated with extrapyramidal symptoms (including akathisia) or emergent depression. More QTP + Li/DVP-treated patients completed the trial, and there was no difference in discontinuation rates due to adverse events between the two groups. Quetiapine, in combination with lithium or divalproex, is well tolerated and has superior efficacy to lithium or divalproex alone in the treatment of bipolar mania.

Adolescent↗
PubMed2003

Hepatocyte growth factor and vascular endothelial growth factor in ischaemic heart disease.

BACKGROUND: Hepatocyte growth factor (HGF) and vascular endothelial growth factor (VEGF) are endothelial cell-specific growth factors, but the production of these growth factors in cardiomyocytes has also been demonstrated. However, there have been no reports focusing their attention on the changes in these growth factors after coronary intervention. We investigated the time-course changes of the serum VEGF and HGF levels in angina pectoris (AP) and acute myocardial infarction (AMI). METHODS: The serum HGF and VEGF levels were measured in 60 patients with AP, in 62 patients with AMI (AP, before heparin administration, and at 24 and 48 hours, and one week after intervention; AMI, before heparin, and at 48 and 72 hours, and one, two, three and four weeks) and in 56 patients with neurocirculatory asthenia as controls. We defined the patients with remodelling who showed an increase in left ventricular end-diastolic volume index (LVEDVI) in the sub-acute phase of AMI. RESULTS: Hepatocyte growth factor levels in the AP and AMI were significantly higher than that in the control (p<0.0001). The AMI level was also significantly higher than AP (p<0.001). In the AMI and AP, HGF peaked at 48 hours. Vascular endothelial growth factor level in the AMI was significantly higher than that in the control and AP (p<0.0001). In the AMI, VEGF peaked at two weeks. There was a significant positive correlation between the peak VEGF and LVEDVI in the sub-acute phase of AMI (p=0.0089, r=0.436). Peak VEGF in the remodelling (+) group was significantly higher than that in the remodelling (-) group (p<0.001). In the AP, VEGF was unchanged. CONCLUSION: While both myocardial and vascular damage contribute to an increase in HGF level, vascular damage is not associated with the increase in VEGF. Vascular endothelial growth factor might be related to left ventricular remodelling in the sub-acute phase of myocardial infarction.

Analysis of Variance↗
PubMed2003

Cytokines in the pathogenesis of cancer cachexia.

PURPOSE OF REVIEW: The aim of the present review is to summarize and update the role of different cytokines in the pathogenesis of cancer cachexia and to provide therapeutic strategies based on cytokine action. RECENT FINDINGS: Cancer cachexia is a syndrome characterized by a marked weight loss, anorexia, asthenia and anemia. The cachectic state is invariably associated with the presence and growth of the tumor and leads to a malnutrition status due to the induction of anorexia or decreased food intake. In addition, the competition for nutrients between the tumor and the host leads to an accelerated starvation state which promotes severe metabolic disturbances in the host, including hypermetabolism, which leads to an increased energetic inefficiency. Different cytokines are clearly implicated in this process, possibly being responsible for anorexia, hypermetabolism and many other metabolic abnormalities, such as muscle proteolysis and apoptosis. SUMMARY: Although the search for the cachectic factor(s) started a long time ago, and although many scientific and economic efforts have been devoted to its discovery, we are still a long way from knowing the whole truth. A lot of progress has been made, however, in understanding the role of different cytokines - tumor necrosis factor and IL-6 in particular - in muscle wasting associated with cancer cachexia, perhaps the most paradigmatic feature of this complex syndrome.

Cachexia↗
PubMed2005

Acoustic and aerodynamic measurement of speech production after supracricoid partial laryngectomy.

BACKGROUND: Supracricoid partial laryngectomy (SCPL) results in laryngeal preservation in more than 95% of patients with T2 glottic carcinoma. After surgery, glottis function is characterized by an absence of vocal cords and poor glottis closure. Voice is an important postSCPL quality of life factor. OBJECTIVE: Enhance postSCPL vocal function. Obtain postsurgical acoustic and aerodynamic measurements and correlate multiple objective parameters with perceptual results. METHOD: Continuous speech voice samples from 61 patients who had undergone SCPL more than 1 year before were scored according to the global, roughness, breathiness, asthenia, and strain (GRBAS) scale by a jury of listeners. Acoustic and aerodynamic parameters were recorded: fundamental frequency (F0), intensity, jitter, shimmer, signal-to-noise ratio (SNR), signal-to-noise ratio greater than 1 kHz (SNR>1), oral airflow (OAF), maximum phonation time (MPT), and estimated subglottic pressure (ESGP). Nonparametric tests and logistic regression analysis were used to compare objective measurements and perceptual evaluations. RESULTS: All patients had various degrees of dysphonia: grade 1, 4.9%; grade 2, 55.7%; and grade 3, 39.4%. Correlations between perceptual grades and objective parameters were obtained for jitter, shimmer, SNR, SNR>1, ESGP, and OAF. No correlations were obtained between the different parameters and age, number of arytenoids, and time elapsed since surgery (TESS). Logistic regression analysis of jitter, SNR, ESGP, and OAF parameters revealed 92.6% agreement with the perceptual evaluation results.

Female↗
PubMedDate not supplied

Childhood bullous pemphigoid: report of a case with life-threatening course during homeopathy treatment.

Bullous pemphigoid (BP) is an autoimmune blistering disorder that may very rarely occur in childhood. We describe a 9-month-old child who developed bullous pemphigoid while she was being treated for presumptive atopic eczema with a homeopathic regimen comprising sulfur, mercury, cantharides, and Rhus (Toxicodendron). She had generalized bullae and a progressive worsening of her general condition with asthenia, dehydration, malnutrition. While the role of homeopathy in triggering the disease remains unclear, our observation attests to the potential life-threatening course of childhood BP in instances where appropriate treatment is withheld.

Dermatitis, Atopic↗
PubMedDate not supplied

Dialysate composition and hemodialysis hypertension.

Dialysis prescriptions have evolved to take advantage of new technology and serve a burgeoning patient population. High-sodium bicarbonate-based dialysate was first formulated in 1982 to enable short, safe, comfortable, high-efficiency hemodialysis (HD). Near-universal adaptation of these high-sodium formulas has virtually eliminated profound dialysis disequilibrium and greatly reduced dialysis discomfort, but has created a syndrome of dialysis salt loading with accentuated postdialysis thirst, interdialytic weight gain, and hypertension. Available technology will soon permit individuals to receive isonatremic dialysis with dialysate customized to the patient's serum sodium activity. Then, rather than choosing between comfortable, safe, high-efficiency dialysis with salt loading; cramps, asthenia, and symptomatic hypotension using low-sodium, high-efficiency rapid HD to control blood pressure (BP) and weight gain; or comfortable, slow, low-efficiency HD with BP control, physicians may be able to minimize symptoms and avoid dialysis salt loading while providing maximum time for rehabilitative activities. The current use of a single sodium activity for all patients ignores the inter- and intraindividual variability in serum sodium activity in our patients. This results in undesired consequences for 20-40% of patients. The application of even more severe salt loading through high-salt sodium modeling only accentuates the long-term problems of excessive thirst, weight gain, and hypertension.

Extracellular Fluid↗
PubMed1990

Omeprazole in the treatment of peptic ulcers resistant to H2-receptor antagonists.

Thirty patients with peptic ulcers resistant to at least 8 weeks of continuous therapy with full-dose H2-receptor antagonists alone or followed by other anti-ulcer drugs, were treated with the gastric proton pump inhibitor omeprazole (40 mg), administered orally once daily for up to 8 weeks. The study design was non-comparative and open; healing was verified by endoscopy. After only 2 weeks of treatment, 21 out of 23 (91%) duodenal ulcer patients were healed, as well as 2 out of 2 patients with both duodenal and gastric ulcer and 1 out of 3 patients with prepyloric ulcer. After 4 weeks, all duodenal ulcers, 1 out of 2 gastric ulcers and 2 out of 3 pre-pyloric ulcers were healed. A further month of therapy healed the gastric ulcer to give an overall healing rate of 97% and leaving only one patient (pre-pyloric ulcer) unhealed at the end of the study. Of 19 patients suffering ulcer symptoms at entry, only two patients reported any symptoms at 2 weeks and one of these (who remained unhealed) continued to have symptoms throughout the study. One patient reported mild asthenia; otherwise, no clinical or biochemical side-effects were recorded. It is concluded that omeprazole is highly effective in healing refractory peptic ulcers.

Adult↗
PubMed1995

The placebo effect in healthy volunteers: influence of experimental conditions on physiological parameters during phase I studies.

1. Although placebo administration is now commonly used as a control condition during clinical pharmacology studies conducted in healthy volunteers, data in placebo-treated subjects usually receive little attention. 2. The profile of several physiological and hormonal parameters was reviewed during the placebo sessions of five double-blind phase I studies involving hospitalisation of healthy volunteers for 2 weeks or more. 3. A clear trend towards an increase in heart rate, which culminated at about 10 beats min-1 at the end of the placebo period was observed, whereas both systolic and diastolic blood pressures remained globally unchanged. 4. Increases in the time to sleep initiation or in asthenia self-ratings during the placebo sessions suggested poor neuropsychiatric tolerability of experimental conditions in some of the studies. 5. In conclusion, all these data confirm that subjects change during the course of these studies. This is an important reason for conducting phase I studies under double-blind placebo-controlled conditions and to refrain from within-group comparisons (vs baseline, first-day effect).

Adolescent↗
PubMed2005

Steady-state pharmacokinetics and pharmacodynamics of CHF3381, a novel antineuropathic pain agent, in healthy subjects.

AIMS: To evaluate the safety, tolerability, pharmacokinetic and pharmacodynamic profiles of CHF3381, a dual NMDA and MAO-A inhibitor, after multiple oral doses in healthy subjects. METHODS: Forty-eight young males received CHF3381 at doses of 100 mg twice daily, 200 mg twice daily, 400 mg twice daily or placebo for 2 weeks according to a double-blind, randomized, parallel group design. Plasma and urine concentrations of the parent drug and of two major metabolites (CHF3567 and 2-aminoindane) were measured over time. MAO-A activity in plasma was estimated by measuring plasma concentrations of 3,4-dihydroxyphenylglycol. Sustained attention, memory and sedation were assessed throughout the study with standard psychometric tests. RESULTS: Most of the adverse events were mild in intensity, with dose regimens of 100 mg twice daily and 200 mg twice daily being indistinguishable from placebo. After 400 mg twice daily, the most frequent adverse events were mild dizziness, asthenia and insomnia. At steady-state, 400 mg twice daily slightly increased supine heart rate (+ 9 +/- 2 beats min(-1)) and diastolic blood pressure (+6 +/- 2 mmHg) compared with placebo. There were no dose-dependent or consistent effects of CHF3381 on attention, motor co-ordination or memory, but 400 mg twice daily significantly decreased alertness compared with placebo. Plasma concentrations of CHF3381 peaked at around 3 h and were dose-proportional. The elimination half-life of CHF3381 was estimated to be 4-6 h. At steady-state, significant CHF3381 plasma concentrations were detected at predose with a modest accumulation (1.3-1.5 times), showing that the drug given twice daily is active over the entire 24 h period. Plasma concentrations of CHF3567 and of 2-aminoindane were also proportional to the dose of CHF3381. CHF3381 dose-dependently inhibited MAO-A activity with peak effects at steady-state of 27 +/- 4%, 46 +/- 2% and 65 +/- 5% after 100 mg twice daily, 200 mg twice daily and 400 mg twice daily, respectively. There were no significant effects of CHF3381 on attention (rapid visual information processing), motor co-ordination (body sway) or memory (learning memory task) at any of the doses. At steady-state, there was a significant decrease in alertness (Bond & Lader visual analogue scale) in the 400 mg twice daily group compared with placebo. CONCLUSIONS: A twice daily regimen of CHF3381 appears to be adequate from a pharmacokinetic and pharmacodynamic perspective. Plasma concentrations reached with 400 mg twice daily exceeded those observed in animals receiving pharmacologically active doses in chronic pain models.

Administration, Oral↗
PubMed1993

Control of prolactin-secreting macroadenomas with parenteral, long-acting bromocriptine in 30 patients treated for up to 3 years.

OBJECTIVE: We investigated the effect of intramuscular injections of long-acting bromocriptine in patients with macroadenomas. STUDY DESIGN AND PATIENTS: Thirty patients with PRL-secreting pituitary macroadenomas were treated with repeated 4-weekly intramuscular injections of 50 or 100 mg of a long-acting, repeatable bromocriptine formulation for six to 37 injections, amounting to a total of 473 injections. Twenty patients received parenteral bromocriptine as primary therapy, ten had persisting hyperprolactinemia after previous therapies including pituitary surgery (n = 7), oral bromocriptine (7), and pituitary irradiation (2). MEASUREMENTS: A PRL day profile was obtained and the patients' clinical status and history were documented, at intervals. Detailed clinical, laboratory, and radiological (pituitary nuclear magnetic resonance or computed tomography scan) evaluations were performed at baseline, after 1 injection and every 6th injection thereafter. RESULTS: In all patients PRL was suppressed from a mean +/- SEM pretreatment level of 32,620 +/- 8680 to 4480 +/- 1140 mU/I on the third day after the first injection. In 12 patients PRL levels normalized (< 400 mU/I) with the first to fourth injection, in three additional patients PRL levels normalized after 8-15 months. In 19 patients PRL was suppressed to less than 1000 mU/l. In three patients PRL did not decrease to less than 50% of pretreatment; in two of them on oral bromocriptine prior to this study there had been a comparable low efficacy. Of 28 patients with macroadenomas (median height 22 mm) tumour shrinkage was evident in 15 by nuclear magnetic resonance or computed tomography scan 28 days after the first injection, and in three additional patients after 6 months. There was further regression in seven cases after 12, 18 or 24 injections. Adenoma size (mean +/- SEM) decreased to 66 +/- 7% of the pretreatment value. The 40 adverse events noted in 20 of 30 patients during 24 hours after the first injection were similar to known side-effects of oral bromocriptine, nausea and postural hypotension being the most frequent. With repeated injections, on average 0.6 adverse events were noted per injection (mostly mild asthenia). There were no local adverse reactions at the injection site. CONCLUSION: We conclude that long-acting repeatable bromocriptine in patients with macroprolactinomas offers a safe and efficacious primary treatment that ensures compliance and gives long-term control. Adverse reactions are comparable to oral bromocriptine but subside with repeated injections.

Adolescent↗
PubMed2005

Quality of life and voice following endoscopic resection or radiotherapy for early glottic cancer.

OBJECTIVES: To assess whether proposed voice and quality of life (QoL) outcome measures were likely to be acceptable to patients previously treated for early glottic cancer by either radiotherapy or endoscopic resection, as well as looking for differences in QoL and voice between treatments. DESIGN: Questionnaire-based cohort study. SETTING: Secondary care, three centres. PARTICIPANTS: All patients treated for T1a or in situ glottic carcinoma between 1997 and 2003. Fifty-three patients were identified; those who had undergone salvage surgery or radiotherapy were excluded. A proportion refused to participate or could not be contacted and two patients had died of unrelated causes. Thirty-six patients completed the trial with 18 from each treatment arm. MAIN OUTCOME MEASURES: Quality of voice as assessed by three questionnaires, Voice Handicap Index (VHI), Vocal Performance Questionnaire (VPQ), Voice Symptom Score (VoiSS) and perceptual analysis of voice by Grade, Roughness, Breathiness, Asthenia and Strained (GRBAS) assessment of vocal recordings. Quality of life as assessed by the Hospital Anxiety and Depression Scale (HADS), University of Washington Quality of Life Questionnaire (UW-QoL), and the Functional Assessment of Cancer Therapy (FACT) questionnaire. RESULTS: All patients included in the trial were able to complete the questionnaires; however, 19% required assistance of some kind. GRBAS assessment showed no difference between groups for any criteria. All QoL questionnaires gave equivalent good scores. All of the voice questionnaires showed no statistical difference between groups except for the emotional subscale of the VoiSS which showed a significantly better score for the radiotherapy arm (P = 0.04). CONCLUSION: All outcome measures were applicable and acceptable to the patient group. Overall QoL and voice appears similar despite treatment arm, apart from the emotional subscale of the VoiSS. A randomized controlled trial is required to further assess this question.

Aged↗