Once-weekly epoetin beta therapy in patients with solid tumours and chemotherapy-induced anaemia: a randomized, double-blind, dose-finding study.

Anaemia is common in patients receiving chemotherapy, causing symptoms that have a major impact on quality of life (QoL). Epoetin beta rapidly increases haemoglobin (Hb) levels and improves QoL in anaemic patients with a variety of tumours. This was a randomized, double-blind, parallel-group, dose-finding study assessing the efficacy and safety of once-weekly epoetin beta in patients with solid tumours receiving chemotherapy. Adult patients with anaemia (Hb < 11 g/dL) were randomized to receive epoetin beta 30,000 IU or 20,000 IU once weekly for 12 weeks. All patients received oral iron supplementation. Haemoglobin levels, transfusion need and QoL [Functional Assessment of Cancer Therapy-fatigue (FACT-F) subscale score] were assessed at regular intervals. Fifty patients were randomized; 30 patients received epoetin beta 30,000 IU once weekly and 20 received 20,000 IU once weekly. Mean (+/- SD) increase in Hb from baseline to week 12 was 1.75 +/- 2.15 g/dL in the 30,000 IU group (P = 0.008 vs. baseline) and 1.04 +/- 1.75 g/dL in the 20,000 IU group (non-significant). Haemoglobin response (increase in Hb >or=2 g/dL from baseline) was observed in 78.3% of patients receiving epoetin beta 30,000 IU and 66.7% receiving epoetin beta 20,000 IU. Improvements in FACT-F subscale score were significantly (P < 0.001) correlated with increases in Hb level. Transfusion use was low during the study in both groups. Both epoetin beta regiments were well tolerated and there were no dose-dependent adverse events. Epoetin beta 30,000 IU once weekly is an effective and well-tolerated treatment of anaemia in patients with solid tumours.

Late relapse of epithelial ovarian cancer: a single institution experience.

PURPOSE OF INVESTIGATION: Late relapses are infrequent in ovarian cancer. We present the characteristics and outcome of patients who relapsed at least five years after first-line chemotherapy. METHODS: Six cases were retrieved from 203 patients treated from 1994 to 1998. RESULTS: Time to recurrence ranged from five to nine years. The initial stage was I or II in all cases, while histology was: endometrioid (4 cases), clear cell (1 case) and unspecified adenocarcinoma (1 case). Only two of five assessable patients responded to chemotherapy. Compared to earlier relapses, late relapses were characterized by earlier stages (p < 0.001), non serous histology (p = 0.010) and absence of symptoms (0% vs 46.5%, p = 0.025) at baseline. Five of 16 relapses (31%) among patients with Stage I or II were late relapses. CONCLUSION: Late relapses of ovarian cancer occur in early stages, where they are relatively frequent, while the chemosensitivity of the disease may be less than expected.

High serum cholesterol levels in persons with 'high-normal' TSH levels: should one extend the definition of subclinical hypothyroidism?

OBJECTIVE: The association between established hypothyroidism and high cholesterol levels is well known. The aim of the present study was to investigate the effect of thyroxine (T4) administration on cholesterol levels in hypercholesterolemic subjects with TSH levels within the normal range ('high-normal' TSH compared with 'low-normal' TSH). DESIGN AND METHODS: We determined TSH levels in 110 consecutive patients referred for hypercholesterolemia (serum cholesterol >7.5 mmol/l). Those with 'high-normal' TSH (2.0-4.0 microU/ml) as well as those with 'low-normal' TSH (0.40-1.99 microU/ml) were randomly assigned to receive either 25 or 50 microg T4 daily for two months. Thus, groups A and B (low-normal TSH) received 25 and 50 microg T4 respectively and groups C and D (high-normal TSH) received 25 and 50 microg T4 respectively. Serum T4, tri-iodothyronine (T3), TSH, free thyroxine index, resin T3 uptake and thyroid autoantibodies (ThAab) as well as total cholesterol, high and low density lipoprotein cholesterol (HDL, LDL), and triglycerides were determined before and at the end of the two-month treatment period. RESULTS: TSH levels were reduced in all groups. The most striking effect was observed in group D (TSH levels before: 2.77+/-0.55, after: 1.41+/-0.85 microU/ml, P < 0.01). Subjects in groups C and D had a higher probability of having positive ThAabs. A significant reduction in total cholesterol (P < 0.01) and LDL (P < 0.01) was observed after treatment only in group D. In those subjects in group D who were ThAab negative, there was no significant effect of thyroxine on cholesterol levels. CONCLUSIONS: Subjects with high-normal TSH levels combined with ThAabs may, in fact, have subclinical hypothyroidism presenting with elevated cholesterol levels. It is possible that these patients might benefit from thyroxine administration.

Systemic sclerosis is not associated with clinical or ambulatory blood pressure.

BACKGROUND: Raynaud's phenomenon is often the first symptom and occurs eventually in more than 95% of patients with systemic sclerosis (SSc). Angiographic studies disclose narrowing and obstruction of the digital arteries, which on autopsy histologic study show prominent subintimal connective tissue proliferation without inflammation, as well as adventitial fibrosis. It is also known that primary cardiac problems include pericarditis, left ventricular or biventricular failure, serious supraventricular or ventricular arrhythmias emerge in patients with SSc. It is not known if these patients present hypertension or hypotension and which parameter of the ambulatory blood pressure may influence such a disease course. METHODS: A total of 85 subjects underwent clinical blood pressure (BP) readings, 24-hour ambulatory BP monitoring, left ventricular assessment by echocardiography and measurement of intima media thickness (IMT) of the right-left internal carotid arteries (RICA and LICA) and right-left common carotid arteries (RCCA and LCCA). The population consisted of 40 subjects with SSc according to the criteria of the American College of Rheumatology (SCL-group) who were not receiving any antihypertensive treatment and 45 healthy volunteers (control group). The two groups did not differ in age. RESULTS: Clinical systolic and diastolic blood pressure, clinical heart rate, mean 24 h systolic blood pressure, SD systolic blood pressure, mean 24 h diastolic blood pressure, SD 24 h diastolic blood pressure, mean 24 h heart rate, SD 24 h heart rate, pulse pressure 24 h, serum glucose, cholesterol, triglycerides, HDL, LDL, creatinine, urea, potassium and natrium did not statistically significant differ between the two groups. Furthermore, the left ventricular mass/BSA and IMT of both carotid arteries did not show a statistically significant difference between the groups. CONCLUSION: Systemic sclerosis is not associated with clinical blood pressure or the parameter of 24 h blood pressure monitoring.

Hyperlipidemia and presence of thyroid autoantibodies in girls with Turner's syndrome or mosaic variance.

OBJECTIVE: The investigation of differences in the medical status between girls with Turner's syndrome or mosaic variance and healthy girls of the same age. In addition, the existence of differences between those persons with full Turner's syndrome and those with mosaic variance were examined. The influence of the treatment was also of concern because a number of the subjects in the study group were being treated with hormones (estrogen and progestin). Investigation concerned cardiovascular abnormalities, bone age, and lipid and hormonal profiles of the participating persons. PARTICIPANTS: Girls came to the hospital with problems in their menstrual cycles. Genetic control (karyotyping) took place. Each patient with symptoms of Turner's syndrome or mosaic variance was included in the study group. Every third patient with no symptoms of the syndromes and near the same age were included in the control group. METHODS: Stratification was made according to the body mass index of the participating persons. Nonparametric tests were used for the analysis. RESULTS: Differences were detected in the levels of cholesterol, low-density lipoproteins (LDLs), high-density lipoproteins (HDLs), and triglycerides, and were increased in the study group. Presence of thyroid autoantibodies, antithyreo-globulin-antibodies (AASTs) and antimicrosomatic antibodies (AASMs), was observed in the study group. In addition, differences were observed in HDL levels between persons with full Turner's syndrome and those with mosaic variance. Finally, significant difference was observed in the level of triglycerides and in the presence of AASTs and AASMs in treated and untreated persons with mosaic variance. CONCLUSIONS: Metabolic, genetic, eating or autoimmune mechanisms are suspected.

Ibandronate is effective in preventing skeletal events in patients with bone metastases from colorectal cancer.

Patients with metastatic colorectal carcinoma (CRC) often develop bone metastases with a high risk of complications. Ibandronate is a novel single-nitrogen bisphosphonate that has been shown to be effective for treating bone metastases from breast cancer. A randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of ibandronate in patients with bone metastases from CRC. The primary efficacy end point was the proportion of patients with skeletal-related events (defined as pathologic fracture, spinal cord compression, radiation therapy to bone, change in antineoplastic therapy or surgery to bone). Secondary end points included time to first skeletal event, skeletal morbidity rate (events/year) and time to progression of bone lesions. In 73 patients with CRC, treatment with intravenous ibandronate 6 mg administered via a 15-min infusion significantly reduced the proportion of patients with skeletal events (39% vs. 78% with placebo; P = 0.019) and prolonged the time to first event by at least 6 months (median >279 vs. 93 days with placebo; P = 0.009). Ibandronate also significantly reduced the skeletal morbidity rate (mean 2.36 vs. 3.14 with placebo; P = 0.018) and prolonged time to progression of bone lesions (214 days vs. 81 days with placebo; P = 0.018). Ibandronate was well tolerated with very rare grade 3 or 4 toxicity. Furthermore, the incidence of renal adverse events was comparable with placebo and there were no clinically relevant changes in serum creatinine. Ibandronate provided significant clinical benefits for patients with bone metastases secondary to CRC. These results indicate that ibandronate may be an effective treatment for patients with metastatic bone disease following CRC. Larger studies are required for further assessment.

The impact of weekly dosing of epoetin alfa on the haematological parameters and on the quality of life of anaemic cancer patients.

The aim of this study was to evaluate the effectiveness and the impact of once-weekly administration of epoetin alfa (Ea) on the management of anaemia and on the quality of life (QOL) of cancer patients receiving chemotherapy. Eighty cancer patients with life expectancy > or = 24 weeks and haemoglobin (Hb) levels < 10.5 g/dL were studied. After an initial screening of patients' demographic and clinical characteristics, Ea 40000 U once a week was administered over a period of 4 months. In case of patients with Hb level exceeding > 14 g/dL or in case of non-response, the dosage was reconsidered. Every month, data regarding Hb levels, clinical variations, changes in the chemotherapy regimen and transfusion use since the last study visit, were evaluated. The Linear Analogue Scale Assessment scale was used for the evaluation of the QOL. The readmissions to hospital rates (P < 0.002) and the transfusion use rates (P < 0.003) were significantly decreased comparatively with baseline. A mean increase from baseline to the final Hb level (P < 0.001) was established, as well as a significant improvement in the functional ability, energy and in the overall QOL (P < 0.001). In conclusion, the treatment of cancer patients with Ea once-weekly is effective and safe, improving their haematological parameters and QOL.

Effects of group psychosocial intervention on coronary risk factors.

The purpose of this study was to investigate whether a psychosocial intervention approach aimed at resolving psychological conflicts could reduce the severity of risk factors for post-acute myocardial infarction patients. Twenty-three patients with a recent myocardial infarction participated in a group psychosocial intervention program which lasted 1 year. Twenty other patients with recent myocardial infarction served as controls. Patients form both groups had regular clinical and laboratory follow-up as well as medication. Mean values for seven risk factors of coronary heart disease (smoking, S; body weight, W; serum cholesterol, C; triglycerides, T; systolic and diastolic blood pressure, SBP, DBP; serum uric acid, U) were compared between the two groups in the 1st, 3rd, 6th and 12th months of the follow-up. The maximal mean improvements of the study versus the control group were as follows: W: -2.82 vs. -1.05 kg; C: -56.04 vs. -6.25 mg/dl; T: -20.61 vs. -2.4 mg/dl; U: -0.57 vs. -0.9 mg/dl; S at 1 year -55.5 vs. -10%. It is concluded that group psychosocial intervention with post-acute myocardial infarction patients considerably reduces some coronary-disease risk factors.

Autonomic nervous system responses to personal stressful events in patients with acute myocardial infarction. Preliminary results.

BACKGROUND: Life events specific for each individual may influence the onset of acute myocardial infarction (AMI), and we wondered whether recall of such events elicits autonomic nervous system responses in patients. METHODS: Thirty-one subjects with AMI, which occurred about 1 month previously (study group), and 22 healthy subjects were interviewed. Whenever the presence of a stressful event was found within the last 2 months before AMI onset, a key phrase of the event was isolated. Each subject was faced with 20 written key sentences (including his/her own sentence if detected) at random order, for 40 s each. At the same time the heart rate (HR) and the galvanic skin response (GSR) were continuously recorded. Pearson r correlations, chi 2 and t tests were employed for comparisons between study and control group as well as within each group. RESULTS: A recent exacerbating event was detected in 30/31 AMI patients and in 0/22 healthy subjects. For the 30 AMI patients the values of HR following the sentence of the suspected event, specific for each patient, were statistically significantly higher than the mean values of HR following the remaining 19 'neutral' statements. The same significant difference appeared with regard to GSR values. The mean values of the AMI patients for the 19 neutral statements did not differ significantly from those of the healthy subjects for the 20 neutral statements, either for HR or GSR. CONCLUSIONS: Findings suggest that recall of personal stressful events elicited autonomic nervous system responses in AMI patients and, therefore, events with personal significance are related to coronary disease onset.

Incidence and evolution of monoclonal gammopathy of undetermined significance (MGUS) in Greece.

Monoclonal gammopathy of undetermined significance (MGUS) is a relatively common condition among individuals older than 70 years. The actuarial risk of MGUS progression to an overt plasma cell malignancy (PCM) after 20 years of follow-up has been reported to be as high as 30%. The purpose of this study was to evaluate the incidence and evolution of MGUS in a Greek population: 1564 consecutive patients older than 50 years who were admitted to the Department of Clinical Therapeutics at the University of Athens School of Medicine for various reasons over a 26-month period were evaluated with serum protein electrophoresis. In cases in which a monoclonal protein was detected, a panel of tests was performed to rule out an underlying plasma cell malignancy (PCM). Serum levels of interleukin (IL)-6, IL-6-soluble receptor (IL-6SR), IL-1 beta, and transforming growth factor beta 1 were also measured in the MGUS cases. Patients with MGUS were monitored at regular intervals for evidence of multiple myeloma or other PCMs. The incidence of MGUS was 4% and there was a positive correlation with increasing age. The median value of serum M peak was only 5.3 g/l. After a median follow-up of 71 months, only two patients developed multiple myeloma (60 and 75 months after initial diagnosis). Our data are consistent with those of other epidemiological studies regarding the incidence of MGUS, but the monoclonal protein levels and the probability of evolution to a malignant plasma cell disorder appeared to be lower in our study than in other series. Our data support the hypothesis that individuals with low M peak values require only regular annual follow-up examinations.

Outpatient treatment of neutropenic fever with oral antibiotics and granulocyte colony-stimulating factor.

In recent years, several cancer patients who developed neutropenic fever were effectively treated on an outpatient basis with either intravenous or oral antibiotics. This approach is associated with reduced cost and improved patient convenience. However, the appropriate antibiotic regimen and the role of growth factors have not been established yet. In order to address these issues we performed a nonrandomized phase II study to assess the feasibility and efficacy of an oral antibiotic regimen in combination with granulocyte colony-stimulating factor (G-CSF) for the outpatient treatment of cancer patients with low-risk neutropenic fever. In 50 patients with solid tumors or lymphoma, 60 episodes of neutropenic fever were treated with the combination of oral ofloxacin 400 mg twice a day, oral amoxicillin 1 g 3 times a day and G-CSF 5 microgram/kg/day subcutaneously. Patients receiving G-CSF prophylaxis were eligible for our study. Oral antibiotics were administered for at least 5 days and G-CSF was continued until resolution of neutropenia. Our patients were ambulatory, hemodynamically stable, and without significant comorbidity. Our combination was successful in 57 episodes (95%) with a median time for fever resolution of 3 days (range: 1-5 days). There was no significant toxicity associated with the antibiotic regimen with the exception of one case of reversible renal impairment. The role of G-CSF in the success of our antibiotic treatment is highly questionable since one half of our patients developed fever while on G-CSF prophylaxis. The combination of oral ofloxacin and amoxicillin with G-CSF is highly effective for the outpatient treatment of cancer patients who develop uncomplicated febrile neutropenia. The relative contribution of G-CSF needs clarification with a prospective randomized study.