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Biomedical subjects

F Roila

Publications and source records attributed to F Roila.

At least 37 records · Page 2Linked to original sources
PubMed1997

5-HT3 receptor antagonists: differences and similarities.

Differences among 5-HT3 receptor antagonists have been reported in pharmacological studies with regard to selectivity of receptor binding, potency, duration of action and dose-response curves. However, whether these pharmacological differences can affect clinical efficacy and safety remains to be determined. A careful analysis of the literature revealed 22 comparative studies among the 5-HT3 receptor antagonists available for review. Unfortunately, several of these trials have some important shortcomings especially in the study design, the size of population studied and the type of anti-emetic treatment selected, making their conclusions often difficult to interpret. However, among these studies, seven large, double-blind clinical trials have clearly shown that the antiemetic activity and tolerability of ondansetron, granisetron, tropisetron and dolasetron is almost identical at least in the prevention of cisplatin-induced emesis. Therefore, from the efficacy and safety point of view, there is no reason to prefer one with respect to the other compound. From the economic perspective, instead, differences may exist and they are strictly related to the dose and schedule of administration chosen for each compound. The information available on the use of 5-HT3 receptor antagonists in the prevention of emesis induced by moderately emetogenic chemotherapy is at best scant. Contrasting results have been reported and only one well-conducted study has been published in full. Therefore, the possible differences among the various compounds are difficult to evaluate. More studies should be carried out in this group of patients.

Antiemetics↗
PubMed1997

Antiemetics revisited.

In the past few years a combination of a 5-HT3 receptor antagonist plus dexamethasone has been shown to be the most efficacious antiemetic prophylaxis of acute emesis induced by cisplatin and moderately emetogenic chemotherapy. In the prevention of cisplatin-induced delayed emesis oral metoclopramide or ondansetron, both combined with dexamethasone, offer similar antiemetic protection. Due to its lower cost the metoclopramide regimen remains the treatment of choice, whereas the ondansetron one is a valid alternative treatment that may be preferred in patients who present acute emesis. In the prevention of delayed emesis induced by moderately emetogenic chemotherapy ondansetron and dexamethasone have been shown superior to placebo. On the other hand, a recent observational study suggested that patients presenting acute vomiting or acute moderate-severe nausea, having a high incidence of delayed emesis, should always receive antiemetic prophylaxis. Instead, patients obtaining complete protection from acute emesis may not require any antiemetic prophylaxis.

Antiemetics↗
PubMed1997

[Evaluation of quality of life in oncology. Rationale and objectives of the first phase of the Quality of Life in Oncology project].

Although the subjective nature of quality of life perception is generally accepted, less attention has been paid to the procedure of selecting domains to be explored with questionnaires. In most cases domains are selected by panel of experts. It is not known whether these domains are relevant for the patients. Moreover, questionnaires developed in 'foreign' countries may not be culturally sound or relevant for patients living in different cultural background. In order to explore what really contributes to quality of life of Italian patients, a survey was conducted with the aim of identifying any dimension of quality of life, positively or negatively impacted on from the illness and therapies. A sample of two hundred and eighty eight cancer patients with previously specified characteristics (primary tumor, stage of disease and place of residence) were identified. After consenting to partecipate to the study, a staff member (a physician, a nurse or a psychologist) asked the patient to complete an open-ended questionnaire in the out-patient clinic or at home. This questionnaire, partially derived from a study by Padilla et al. made up of 5 questions: 'What does the term quality of life mean to you?', 'What contributes to a good quality of life?', 'What contributes to a poor or bad quality of life?', 'Which either physical or psychological symptom interferes with your quality of life?', 'State any positive or negative change in your quality of life, due to illness or treatments'. The first question was asked to explore the meaning of quality of life for the patient; the second and third question were asked to determine the contents of quality of life not health related; the fourth question and the diary provided information about quality of life contents related to his own experience of disease. Two hundred and forty eight questionnaires (86.1%) were obtained from 7 Cancer Centres participating to the study (Genova, Milano, Roma, Perugia, Napoli, Cagliari, Palermo). All the questionnaires were transcribed and subsequently broken down in phrases on a form that allowed coding. Three raters (a research nurse, an oncologist and a clinical psychologist) made the content analysis using as conceptual framework the list of domains identified by the Italian Society of Psycho-Oncology. The present study shows the possibility to define the content domain of quality of life attributes for cancer patients, using patients as experts.

Adolescent↗
PubMed1997

[Recent improvements in antiemetic therapy].

In the past few years important progress in the prevention of chemotherapy-induced nausea and vomiting has been made mainly thanks to the introduction of the 5-HT3 receptor antagonists in clinical practice (ondansetron, granisetron, tropisetron). In the prevention of acute emesis induced by cisplatin, an intravenous combination of a 5-HT3 receptor antagonist plus single dose dexamethasone (20 mg) should be considered the treatment of choice. This is also the case in the prevention of acute emesis induced by moderately emetogenic chemotherapy (intravenous cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination), but high and repeated doses of dexamethasone should be used (8 mg intravenously plus 4 mg orally every 6 hours for four doses starting contemporarily to chemotherapy administration). Several-well conducted double-blind comparative studies among intravenously administered 5-HT3 receptor antagonists have been carried out. Almost all showed that they have identical antiemetic activity and tolerability. Therefore, the choice among 5-HT3 receptor antagonists should be based only on their acquisition cost in each country. In the prevention of delayed emesis (from day 2 to day 4) induced by cisplatin oral metoclopramide (0.5 mg/kg or 20 mg every 6 hours for four doses daily) and oral ondansetron (8 mg twice daily), both combined with dexamethasone, showed similar antiemetic efficacy. Metoclopramide plus dexamethasone should be considered the antiemetic regimen of choice due to its lower cost. Ondansetron plus dexamethasone is a valid alternative regimen that should be preferred in patients who not tolerate metoclopramide and in patients who suffer from acute vomiting. In the prevention of delayed emesis induced by moderately emetogenic chemotherapy oral dexamethasone or oral ondansetron showed a good antiemetic efficacy, but the results from a recently published study seem suggest the necessity to treat only patients who present acute vomiting or moderate-severe nausea. In fact, patients obtaining complete protection from vomiting and nausea (or at most mild acute nausea) have a very low incidence of delayed emesis.

Antiemetics↗
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↗
PubMed1996

Control of acute cisplatin-induced emesis over repeat courses of chemotherapy. Italian Group for Antiemetic Research.

There have been few studies to determine whether the efficacy of antiemetics is maintained over repeated courses of cisplatin chemotherapy. Two large controlled studies have been undertaken by our group to address this issue. A comparison of the standard high-dose regimen of metoclopramide plus methylprednisolone versus a higher dose regimen of metoclopramide plus dexamethasone and diphenhydramine showed that the latter regimen was significantly more efficacious with regard to complete control of nausea and vomiting in chemotherapy-naïve patients. However, this difference was not maintained over repeated courses of chemotherapy. A comparison of metoclopramide and dexamethasone plus diphenhydramine with ondansetron plus dexamethasone showed that the ondansetron regimen provided even greater control of vomiting, which was maintained over subsequent cycles of chemotherapy. Various factors were analysed in both studies to determine whether they had any effect on treatment outcome. In general, age < 50 years, female gender, and higher doses of cisplatin were associated with an increased risk of emesis. However, the most significant prognostic factor was emesis response in the previous cycle. It is therefore important to aim for good antiemetic control in the first cycle of cisplatin chemotherapy.

Aged↗
PubMed1995

Ondansetron clinical pharmacokinetics.

Ondansetron is a potent and highly selective serotonin 5-HT3-receptor antagonist which has demonstrated important antiemetic activity and good tolerability in the prevention of chemotherapy-induced nausea and vomiting. Ondansetron is completely and rapidly absorbed from the gastrointestinal tract after oral administration, and does not accumulate with repeated oral administration. Owing to hepatic first-pass metabolism, its bioavailability is only about 60% compared with ondansetron administered by infusion over 15 minutes. Bioavailability is slightly increased when administered after a standard meal, and is not influenced by coadministration of antacids; a slightly enhanced bioavailability has been observed in patients with cancer. Since the time to reach peak concentration is 0.5 to 2 hours after oral ingestion, the drug should be administered at least 30 minutes before chemotherapy. Possible alternative ways of administration of ondansetron include intramuscular, subcutaneous and rectal administration, and oral controlled-release formulations. Ondansetron is widely distributed (volume of distribution approximately 160L) and binds moderately (70 to 76%) to plasma proteins; the elimination half-life averages approximately 3.8 +/- 1 hours. Clearance occurs by hepatic metabolism (95%) rather than renal excretion. Metabolites do not play a role in the activity of the drug, and there is no evidence of genetic polymorphic metabolism. Although aging is associated with decreased clearance and increased bioavailability, dosage adjustments are not required for the elderly, and may be necessary only in patients with severe hepatic impairment. Chemotherapeutic agents do not seem to modify the pharmacokinetics of ondansetron. There remains the question of whether control of emesis is related to systemic availability of ondansetron and, in consequence, the optimal dose and schedule of ondansetron is still to be identified with certainty.

Animals↗
PubMed1994

Are there differences among the serotonin antagonists?

The serotonin-receptor (5-HT3) antagonists combined with dexamethasone are considered the antiemetic therapy of choice in the prevention of cisplatin-induced emesis. As there are now several compounds on the market, the dilemma of preference is particularly relevant. In preclinical studies some differences among the three marketed drugs (ondansetron, granisetron and tropisetron) have emerged. In particular, tropisetron and granisetron have a greater potency and duration of action and seem to have a greater selectivity toward the 5-HT3 receptor with respect to ondansetron. Furthermore, while with tropisetron and granisetron there is a linear dose/response relationship, this does not seem to be the case for ondansetron. These preclinical differences, however, do not seem to correlate with the clinical antiemetic activity of these compounds. In fact, although the number of comparative studies is small, with all of them presenting several shortcomings (small number of patients, not blinded studies, no association with steroids, sponsored trials), it seems that the antiemetic activity and tolerability of ondansetron, granisetron and tropisetron is very similar. If these data are confirmed, the least expensive of the 5-HT3 antagonists should be the drug of choice. We feel, however, that the answer to this rather difficult question of choice will come from very large, independent, methodologically correct studies designed to show small but clinically significant differences (i.e., less than 10% in complete protection from emesis). These trials, which require about 1000-1500 patients, are ongoing and the one carried out as a multicenter study by the Italian Group for Antiemetic Research is close to conclusion.

Animals↗
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↗
PubMed1993

Reducing chemotherapy-induced nausea and vomiting. Current perspectives and future possibilities.

Nausea and vomiting are among the most distressing adverse effects of cancer chemotherapy. In the last 10 years considerable advances in the prevention of chemotherapy-induced emesis have been made. From an analysis of the results obtained in patients receiving moderately- to severely-emetogenic drugs the following guidelines in choosing the best antiemetic treatment can be given: 1. For the prevention of acute emesis induced by a high single dose of cisplatin (> or = 50 mg/m2) or by low doses (20 to 40 mg/m2) repeated for 4 to 5 days, the combination of ondansetron plus dexamethasone is the most efficacious and least toxic antiemetic therapy. 2. For the prevention of delayed emesis the combination of oral dexamethasone plus metoclopramide seems to offer the best protection, although over 40% of patients still experience delayed nausea and vomiting. 3. For the prevention of acute emesis induced by moderately emetogenic drugs, corticosteroids (dexamethasone or methylprednisolone) are efficacious and safe antiemetic agents. Although equally efficacious, the serotonin (5-HT)3 receptor antagonists, due to their higher acquisition costs, are indicated only in patients refractory to corticosteroids or in those who cannot use them. Unresolved problems in antiemetic research include: (i) identification of the best antiemetic treatment for those areas of cancer chemotherapy where adequate data are lacking, such as high dose regimens for bone marrow transplantation; (ii) optimisation of treatment for the most widely used chemotherapy regimens; and (iii) identification of the best rescue treatment for patients who fail to respond to antiemetic prophylaxis. Although many new 5-HT3 antagonists are currently being studied, the possible improvement in efficacy and tolerability brought about by these agents will probably only be marginal.

Antiemetics↗