Search PubMed⌕ Search

Biomedical subjects

E Ballatori

Publications and source records attributed to E Ballatori.

At least 37 records · Page 2Linked to original sources
PubMed1996

Comparative studies of various antiemetic regimens.

Since 1981, when high-dose intravenous metoclopramide was demonstrated to be efficacious, slow but constant improvement in the prevention of chemotherapy-induced emesis has been achieved. Today, a combination of a serotonin receptor 3 (5-HT3) antagonist plus dexamethasone can be considered the most efficacious treatment for the prevention of emesis induced by cisplatin and by moderately emetogenic chemotherapy. Which 5-HT3receptor antagonist should be used? Preclinical differences among 5-HT3receptor antagonists have been reported with regard to selectivity of receptor binding, potency, dose response, and duration of action. Twelve comparative studies among 5-HT3receptor antagonists have been carried out. Unfortunately, all these trials have some important shortcomings (patient population not large enough to show small but clinically important differences; not blinded studies; no association with steroids to maximize treatment efficacy) and, therefore, no definitive conclusions can be drawn. Very recently three large, well-conducted double-blind comparative studies have been published. All three showed that 5-HT3receptor antagonists have almost identical antiemetic efficacy and tolerability. Therefore, the choice among the 5-HT3receptor antagonists should be based only on the acquisition cost of the prescribed dose in each country for each compound.

Antiemetics↗
PubMed1996

Methodology of trials with antiemetics.

Chemotherapy-induced nausea and vomiting can today be controlled with the "new" antiemetics or with their various combinations in a high percentage of patients. Despite this, for some subgroups of patients, certain chemotherapy regimens and some aspects of the phenomenon (delayed presentation), emesis remains a critical problem. Hence, there is the necessity for a continuous effort in the search for new drugs or better treatment modalities and the absolute requisite that these efforts be carried out according to a sound and verified trial methodology. Nausea and vomiting induced by antineoplastic agents are extremely variable phenomena, depending not only on the characteristics of chemotherapy regimens and of the patient population, but also on a subjective feeling generated by the impact of the care system on the patient's individual situation. Therefore, precisely because of this high variability, large comparative trials should be carried out to ensure that the sample is sufficiently representative for the most efficacious antiemetic regimen to be detected. In this field, some of the main problems arising in all clinical trials have their own specificity, particularly the study design, whether completely randomized or cross-over, the follow-up and the importance of prognostic factors. Among these, age, gender and previous chemotherapy with experience of nausea and vomiting have been confirmed as important. In addition, some topics must clearly be highlighted: the definition of the response variables and the assessment of variability of the results obtained with the same antiemetic regimen from one cycle of chemotherapy to the next (i.e. persistence). The greater attention devoted today to delayed emesis raises some methodological questions: this paper suggests some possible solutions for a better evaluation of this phenomenon.

Antiemetics↗
PubMed1994

Antiemetics in cancer chemotherapy: historical perspective and current state of the art.

Chemotherapy-related nausea and vomiting can today be controlled with available antiemetics in a high percentage of patients but emesis remains a problem for some patients, with certain drugs and with repeated cycles of chemotherapy. The fundamental steps of clinical research in antiemetics towards the improvement of the control of nausea and vomiting with new drugs or combinations are presented. Special emphasis is given to cisplatin-induced nausea and vomiting because of the frequency and relevance of this phenomenon. The use of high-dose metoclopramide, its combination with steroids, and later the addition of lorazepam or diphenhydramine represented the evolving standard of the 1980s, with the level of complete protection from vomiting improving from 30%-40% to 60%-70% with the three-drug combination. The introduction of new agents such as the 5-hydroxytryptamine 3 (5-HT3) receptor antagonists has recently offered new possibilities because of their activity and lack of toxicity. In particular, the combination of ondansetron plus dexamethasone is today the most efficacious and least toxic antiemetic treatment for prevention of emesis in patients treated with a single high dose or low repeated doses of cisplatin. A comparison of different 5-HT3 antagonists, always in combination with steroids, is now considered necessary. For patients treated with moderately emetogenic chemotherapy the use of steroids can still be considered the standard treatment. In this setting, the role of 5-HT3 receptor antagonists, alone or in combination with steroids, has to be better defined through large, well-planned clinical trials, which should have a cost-effectiveness analysis as one of their goals.

Antiemetics↗
PubMed1994

Cost and cost-effectiveness analysis of ondansetron versus metoclopramide regimens: a hospital perspective from Italy.

In a large double-blind study of antiemetic therapy conducted in Italy, 289 patients underwent 3 consecutive cycles of cisplatin chemotherapy. Antiemetic treatment with ondansetron plus dexamethasone was more efficacious and better tolerated, but also more expensive, than treatment with metoclopramide plus both dexamethasone and diphenhydramine. To evaluate the different costs of the 2 antiemetic regimens, we conducted a retrospective cost-effectiveness analysis from a hospital perspective. Direct costs of antiemetic therapy (acquisition cost of drugs, materials and time spent by nurses to prepare and administer therapies), cleanup after emesis, rescue medication and adverse events were evaluated. Antiemetic drug acquisition costs per patient were 5.23-fold higher for the ondansetron regimen than for the metoclopramide regimen. However, when the costs of materials and nursing time required to prepare and administer the antiemetic regimens were included, this ratio was 3.77. Furthermore, including the cost of emesis, rescue antiemetic treatments and medication used to treat adverse events, hospital costs per patient were 3.21-fold higher with the ondansetron regimen during the first cycle, 3.08-fold higher during second cycle and 2.89-fold higher during third cycle of chemotherapy. Complete protection from vomiting and from both vomiting and nausea with ondansetron occurred, respectively, in 78.7 and 69.1% of patients in the first cycle, 73.8 and 57.3% in the second cycle, and 74.2 and 58.1% in third cycle of chemotherapy. Corresponding figures for the metoclopramide regimen were 59.5 and 50.4%, 53.6 and 37.1%, and 46.8 and 27.3%, respectively. Thus, the cost per successfully treated (completely protected) patient was 2.43- and 2.34-fold higher, respectively, for ondansetron at the first cycle, 2.23- and 1.99-fold higher, respectively, at second cycle, and 1.82- and 1.36-fold higher, respectively, at third cycle. In conclusion, the study demonstrates that, while ondansetron has a greater acquisition cost than metoclopramide, the ondansetron regimen costs per successfully-treated patient substantially decrease when all direct hospital costs are taken into account.

Chemotherapy, Adjuvant↗
PubMed1993

Ondansetron.

Ondansetron is the first selective antagonist of the 5-hydroxytryptamine receptors (type 3) marketed for the prevention of emesis induced by antineoplastic agents. Ondansetron has been shown to be more active and less toxic than high-dose metoclopramide in patients submitted to cisplatin chemotherapy. Furthermore, when dexamethasone was added to ondansetron, its antiemetic efficacy increased significantly. In the prevention of emesis induced by a high single dose of cisplatin or by repeated low doses, ondansetron combined with dexamethasone has been shown to be the more efficacious and less toxic antiemetic treatment. However, in the prevention of delayed emesis from cisplatin, its role is still to be defined. In patients submitted to moderately emetogenic chemotherapeutic agents, ondansetron has shown an efficacy superior or equal to standard doses of metoclopramide, but is less toxic. Moreover, when compared with dexamethasone, its antiemetic efficacy and tolerability is similar; in this group of patients ondansetron should be used only when steroids fail. Ondansetron toxicity is generally mild; in particular, it does not induce extrapyramidal reactions. The most frequent side-effects are headache and constipation.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1993

Reliability and validity of a quality of life questionnaire in cancer patients.

Two studies were sequentially conducted to validate a new questionnaire which takes into consideration the most important variables which could influence quality of life evaluation. Particular attention was given to the methodology employed to collect data and to the patients' characteristics. In the first study 80 consecutive cancer patients were randomised to twice fill in one of four different types of questionnaire, each one characterised by a different polarisation of semantic and syntactic extreme values of the visual linear analogue (for instance, "very much" always on the right, regardless of the semantic value of the answer; positive semantic value always on the right, regardless of whether it was "very much" or "not at all"; and so on). The second study, conducted on 60 lung cancer patients, consisted in testing the reliability (by measuring the reproducibility in different ways) and the validity (by performing a factor analysis) of the type of questionnaire indicated by the first study as the most reliable. The internal coherence was also evaluated by measuring the effects of physical and psychological conditions on the responses.

Adult↗
PubMed1991

Intra and interobserver variability in cancer patients' performance status assessed according to Karnofsky and ECOG scales.

The Karnofsky (K) and ECOG (E) performance status (PS) scales are widely used to evaluate the functional status of cancer patients to determine their eligibility for clinical trials and their prognosis, but knowledge of inter and intraobserver variability of these scales is scarse. We therefore planned a prospective study on 209 consecutive cancer patients to evaluate this critical point. Two independent observers evaluated the KPS and EPS of each patient by interviewing them on the same day. After their interviews the patients were asked to fill in, again on the same day, a self-evaluation scale concerning their ability to perform the routine activities of daily life. The 209 patient self-evaluation scales were presented twice, randomly and blinded, to the two observers who had participated in the evaluation of PS as well as to one other observer who had not. The interobserver correlation for both scales was very high (K = 0.921 for KPS and K = 0.914 for EPS) as was the intraobserver correlation (for KPS: K = 0.993, K = 0.960, and K = 0.959 and, respectively, for EPS: K = 0.982, K = 0.970, and K = 0.920). On the basis of these results, it appears that evaluation of PS made by a clinical oncologist using K or E scales can be very reliable and is a guarantee of optimal selection of cancer patients for inclusion in clinical trials.

Aged↗
PubMed1991

Predictive factors of delayed emesis in cisplatin-treated patients and antiemetic activity and tolerability of metoclopramide or dexamethasone. A randomized single-blind study.

To prevent delayed emesis induced by cisplatin (mean dose 90 mg/m2), 120 consecutive patients were randomized to receive, in a 7-day crossover design, oral metoclopramide (20 mg q.i.d.), dexamethasone (1 mg q.i.d.) or placebo (two tablets q.i.d.) starting 24 hours after the end of chemotherapy. Complete protection from nausea, but not from vomiting. was significantly increased by both dexamethasone and metoclopramide with respect to placebo. Important prognostic factors favoring the appearance of delayed emesis were incomplete protection from vomiting during the first 24 hours after cisplatin, female gender, and highest cisplatin doses. Tolerability of both drugs was good. Larger and randomized controlled trials are necessary to identify better preventive treatment of delayed emesis induced by cisplatin.

Cisplatin↗
PubMed1990

Assessment of nausea.

In a standardized way three different methods of measuring nausea have been assessed in 849 patients enrolled in 4 double blind, randomized, clinical trials, and 2 observational studies. Nausea was measured before and 2, 4, 6, 8 and 24 hours after cancer chemotherapy by using a discrete scale (DS), a visual analogue scale (VAS) and a continuous chromatic analogue scale (ACCS), and it was evaluated according to 4 different dimensions: maximal intensity (MI) entity (E) duration (D) and quantity (Q). The distributions of nausea measurements in the population, agreement between the scales and their sensitivity, and agreement between dimensions and their sensitivity were analyzed. A uniform distribution of nausea measurements was found only in patients receiving chemotherapy without any antiemetic treatment. There was substantial equivalence of the different scales, and no advantage was shown an using an analogue (VAS) than a discrete (DS) scale. A trend toward increasing sensitivity in detecting differences as the dimensions of nausea considered became more inclusive of the various aspects of this symptom (Q more sensible than E more sensible than MI) was observed.

Antiemetics↗
PubMed1990

A pilot study of metoclopramide, dexamethasone, diphenhydramine and acupuncture in women treated with cisplatin.

A total of 26 women who submitted to cisplatin chemotherapy received as antiemetic treatment a combination of metoclopramide, dexamethasone and diphenhydramine. Acupuncture according to traditional Chinese medicine was also carried out. The results were compared with those obtained in a similar group of women with cancer, who were treated in the same setting with the same antiemetic combination but without additional acupuncture. Acupuncture was shown to increase complete protection from nausea and to decrease the intensity and duration of nausea and vomiting. However, the difficulties of performing acupuncture routinely in daily practice are a hindrance to its wider use.

Acupuncture Therapy↗
PubMed1990

A randomized trial fo three cisplatin-containing regimens in advanced non-small-cell lung cancer (NSCLC): a study of the Umbrian Lung Cancer Group.

Survival in patients with locally advanced (stage III Mo) and metastatic (Ml) non-small-cell lung cancer (NSCLC) is short. Phase II studies have reported objective responses ranging from 20% to 60% using cisplatin-based chemotherapeutic regimens, yet few have shown improvement in median survival. In our phase II pilot studies with cisplatin (CDDP) and etoposide (VP-16), we observed a 26% response rate; with CDDP, VP-16, and mitomycin-C, a 38% response rate was obtained in advanced NSCLC patients. A total of 156 consecutive patients with locally advanced and metastatic NSCLC were randomized to one of three treatment arms to determine whether the chemotherapy protocols had any effect on response rate and median survival in a large, randomized study. Arm 1 consisted of CDDP (120 mg/m2 x 3 weeks); arm 2, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 given i.v. on days 1-3), repeated every 3 weeks; and arm 3, of CDDP (120 mg/m2) and VP-16 (100 mg/m2 on days 1-3) given every 3 weeks, plus mitomycin C (10 mg/m2 on days 1, 21, and 42, then every 6 weeks, for a maximal dose of 100 mg). After 71 patients had been enrolled in the study, we stopped accrual in the CDDP arm due to a lack of response [1 complete response (CR) in 24 patients; 4%] and continued enrollment in the two combination-chemotherapy arms. In the CDDP/VP-16 arm a 30% response rate [1 CR, 18 partial responses (PRs)] was obtained, and in the CDDP/VP-16 mitomycin C arm a 26% response rate (4 CRs, 11 PRs) was seen among a total of 150 evaluable patients. Responses were observed in 31% of patients with favorable performance status (PS) (ECOG 0-1) vs 14% in patients with a poor PS (ECOG 2-3). Of patients with locally advanced disease (III Mo), 17 (33%) obtained an objective response, compared with 20 patients (20%) with metastatic disease. Median survival was 18 weeks in the CDDP arm, 35 weeks in the CDDP/VP-16 arm, and 37 weeks in the CDDP/VP-16/mitomycin C arm. The median survival in the multimodal chemotherapy arms was significantly greater than that obtained with CDDP alone. Toxicity was predominantly myelosuppression in the mitomycin C-containing arm (27%, wtto grade 3-4). Our study shows that combination chemotherapy using CDDP/VP-16 is active and safe in the treatment of advanced NSCLC patients with a good performance status. The addition of mitomycin C did not improve the therapeutic response.

Adult↗
PubMed1990

Neuroendocrine markers in aging brain: clinical and neurobiological significance of dexamethasone suppression test.

The dexamethasone suppression test (DST) is commonly accepted as an indicator of hypothalamus-pituitary-adrenal (HPA) axis functioning in clinical practice. In this study, DST was carried out in a geriatric population composed of patients with dementia of Alzheimer type (DAT), stroke and age-matched controls. The stress state of the subjects was also functionally assessed by the Symptoms Rating Test (SRT). The results disclosed no significant differences in basal cortisol levels in the three groups. A positive correlation between age and log-transformed basal cortisol levels was found in the entire population as well as in each group. After dexamethasone administration, 20% of controls, 49% of DAT patients, and 48% of stroke patients were non-suppressors. At 8.00 a.m. and 11.00 p.m. after dexamethasone, cortisol levels were significantly lower (p less than 0.02) in controls than in pathological groups. A significant positive correlation between age and symptoms of depression and anxiety was found. One-third of stroke patients showing lesions in the right hemisphere were non-suppressors, and presented mostly subcortical infarcts, while 1/4 of them had depressive disorders. This study demonstrated a progressive increase in basal cortisol levels and depressive symptoms with age, a poor diagnostic value of DST in age-related pathological conditions such as DAT and stroke, and the role of these cerebral pathologies in amplifying the neuroendocrine dysregulation due to the ageing process itself. DST is a useful biological marker for disclosing the vulnerability of the ageing brain, but it has no diagnostic value.

Aged↗
PubMed1990

A pilot study of metoclopramide, dexamethasone, diphenhydramine and lorazepam in prevention of nausea and vomiting in cisplatin-treated male patients.

In a pilot study we evaluated the efficacy and tolerability of a four-drug antiemetic combination (metoclopramide, dexamethasone, diphenhydramine and lorazepam) in cancer patients submitted to cisplatin chemotherapy at doses greater than or equal to 50 mg/m2. Fifty male patients entered the study. Complete protection from vomiting and nausea was obtained in 41 patients (82%) (95% confidence limits 71 and 93%). Toxicity was slight except for moderate sedation in 10% of patients necessitating their hospitalization. Only one extrapyramidal reaction (akathisia) was observed. When these results were compared to our previous experience in male patients treated with a combination of metoclopramide, dexamethasone and diphenhydramine without lorazepam, used at the same doses and schedule, no clear benefit and higher toxicity was observed.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1989

Antiemetic activity of high-dose metoclopramide combined with methylprednisolone versus metoclopramide alone in dacarbazine-treated cancer patients. A randomized double-blind study of the Italian Oncology Group for Clinical Research.

In a double-blind randomized trial, we compared the efficacy and tolerability of high-dose (2 mg/kg X 4) intravenous metoclopramide (MTC) versus metoclopramide plus high-dose (250 mg X 2) intravenous methylprednisolone (MP) administered for the first 2 days in untreated patients submitted to dacarbazine chemotherapy for 5 days. Thirty-four patients entered the study. Complete protection from nausea and vomiting was achieved in the majority of patients all through the study period with both antiemetic treatments, with slightly greater efficacy at day 2 for the combination. However, after suspension of the antiemetic therapy, there was a relapse of vomiting in patients. Side effects were not different between the two treatments, but extrapyramidal reactions were significantly increased on the second day of antiemetic therapy. In conclusion, high-dose MTC with or without MP can give good antiemetic protection and the combination seems to be slightly more efficacious. However, the relapse of vomiting after discontinuing antiemetic treatment and the high incidence of extrapyramidal reactions justify further studies to find a better antiemetic treatment.

Dacarbazine↗
PubMed1988

A randomized trial to evaluate the immunorestorative properties of thymostimulin in patients with Hodgkin's disease in complete remission.

A total of 19 Hodgkin's disease (HD) patients (12 male, 7 female) aged 26-67 years, who had been in complete unmaintained remission for 6 months or more when the study was initiated, were randomly given 50 mg thymostimulin (TS) i.m. daily (G1) or every other day (G2) for 35 days. A third group (G3) was not treated. Then TS, at the same dose was administered twice a week for the following 22 weeks in patients both initially receiving loading or intermittent TS treatment. When compared with age- and sex-matched controls, as a group, the patients' circulating OKT3+, OKT4+, OKT11+ and E-AETR+ cells were depressed (P less than 0.001 for both proportions and absolute numbers), whereas their OKT8+ cell population was not. Following 5 weeks of daily TS administration, the proportions and numbers of all T cell fractions significantly increased in G1 patients (P less than 0.03 for all the comparisons tested), while following intermittent TS treatment (G2) only the proportions of OKT3+ and OKT11+ cells (P less than 0.03), but not of other T cell fractions, significantly increased. In addition, no significant changes in the absolute numbers of T cell fractions were observed in this group of patients. Furthermore, no spontaneous variations in the T cell pool size occurred in untreated patients. TS maintenance therapy did not produce any further improvement in the size of overall T cells and T cell subsets but sustained percentage and absolute numbers of these cells during administration and the absolute number of T cells even after discontinuation of therapy. The TS-induced improvement in the T cell pool was not associated with any change in the size of circulating non-T lymphocytes and monocytes. In vitro phytohemagglutinin-induced interleukin-2 (IL-2) and gamma-interferon (IFN-gamma) synthesis was assessed in 11 patients (3 G1, 4 G2, and 4 G3). Although it was not statistically significant, a rise in IL-2 and IFN-gamma production was observed in TS-treated patients, but not in untreated controls. TS failed to exert any effect on the serum circulating levels of neopterin, type I and II IFN, beta-2 microglobulin (B2-M) and immunoglobulins (Ig). TS can thus improve defective T cell frequences and numbers and may modulate IL-2 and IFN-gamma production.

Adjuvants, Immunologic↗