Antiemetic Guidelines Research Articles

The Importance of Continuous Quality Assessment: A Lesson from Antiemetic Guidelines for Preventing Chemotherapy-Induced Nausea and Vomiting

At the University of Maryland Marlene and Stewart Greenebaum Cancer Center, we noticed that patients did not routinely receive a guideline recommended antiemetic regimen for the prevention of chemotherapy induced emesis. To achieve better compliance, treatment guidelines were incorporated into chemotherapy preprinted orders. The purpose of this study is to evaluate outcomes in the delayed period following highly emetogenic chemotherapy in patients receiving a guideline recommended antiemetic regimen. Outcomes were compared to a historical cohort of patients who did not receive a guideline recommended regimen. This prospective, observational, quality-assessment study enrolled patients receiving highly emetogenic chemotherapy who received a standard delayed antiemetic regimen of dexamethasone for 5 days plus dolasetron for 3 days. Patients documented the number of emesis episodes, breakthrough nausea with medication use, and adverse effects. Quality of life was measured using the Modified Functional Living Index – Emesis. Originally, 40 to 60 patients were planned to be studied. This study was stopped early, because national consensus guidelines for preventing chemotherapy induced nausea and vomiting were recently updated and no longer recommended this regimen. Overall, the incidence of vomiting was statistically similar ( P= 0.4) in the prospective study cohort (77.8%) vs the historical cohort (65.2%). Also, breakthrough antiemetic use was similar in both groups. Complete response was similar between the two groups (27.8% current, 30.4% historic). Outcomes were similar in the current study vs the historical cohort. The institution's guidelines were modified and further studies will assess the efficacy of newer antiemetic regimens using these data as historical control.

Effect of nausea vs. vomiting on patients’ quality of life during chemotherapy

8514 Background: Antiemetic guidelines are based largely on the presumption that vomiting is of greater concern to cancer patients, and impacts their quality of life (QOL) more strongly, than nausea. We examined the relative influence of chemotherapy-induced nausea and emesis on patients’ overall QOL and on the specific domains of social, emotional, physical and functional well-being. Methods: 667 patients enrolled in a three-arm, randomized, controlled Phase III study that detected no difference in the ability of a serotonin receptor antagonist vs. prochlorperazine (given regularly three times daily or taken only as needed for symptoms) to control the severity of nausea, completed the FACT-G before treatment and on the third day following their first infusion of anti-cancer chemotherapy containing doxorubicin (Day 4 of cycle 1). 93% were female, and 90% had breast cancer. Results: There was a significant reduction in overall QOL and in physical and functional well-being, but no significant change in emotional or social well-being, over the four day period. In a stepwise linear regression analysis predicting change in overall QOL, average nausea severity entered first and accounted for 24% of the variance in reduced QOL (p < 0.001). Occurrence of vomiting (yes, no) accounted for a non-significant less than 1% of additional variance (p = 0.240). No other factors (gender, age, the degree to which patients expected to experience nausea or vomiting, whether or not nausea or vomiting occurred, and maximum nausea severity over the four days) were significant predictors of the reduction in QOL. Similar results were obtained when the relative influence of nausea and vomiting on physical and functional decline were studied. Conclusions: Severity of nausea, not the occurrence of vomiting, was the key factor in patients’ perceived decline in quality of life in the days immediately following chemotherapy infusion. Nausea severity should be a primary outcome measure in studies evaluating antiemetic efficacy. Supported in part by NCI Public Health Service grant U10 CA37420 and ACS grant RSG-01–071-PBP No significant financial relationships to disclose.

Outcomes and health status of patients undergoing usual care for highly emetogenic chemotherapy

18591 Background: Chemotherapy-induced nausea and vomiting (CINV) remains a significant issue for patients, especially management of delayed symptoms. The Perugia 2004 antiemetic guidelines recommended that anthracycline/cyclophosphamide (A/C) combination regimens be considered as high risk emetogenic potential. The aim of our study was to determine the extent of CINV, and effect on quality of life for chemotherapy-naïve patients in a practice-based environment. Methods: Eligible patients were receiving their 1st cycle of high risk emetogenic or carboplatin chemotherapy, administered with “standard care” (5HT3 antagonist + dexamethasone) antiemetics (use of NK1 antagonists excluded). Patients completed a daily diary for 5 days post chemotherapy, capturing data on CINV activity and rescue medications usage. Emesis and nausea-specific health status was measured by the Functional Living Index - Emesis (FLIE); general health status was assessed using a 100mm VAS (EQVAS). Results: Of 74 patients, 42 received an A/C regimen, 16 cisplatin and 16 carboplatin. Overall complete response (no vomiting, no use of rescue antiemetics during the study period) was 60% in patients receiving carboplatin, 24% A/C and 21% cisplatin. During the delayed phase, mean total emesis episodes for carboplatin was 0.6, A/C 2.21 and cisplatin 4.08. Patients receiving carboplatin reported less delayed nausea, and better outcomes for FLIE and EQVAS scores. Treatment with either A/C or cisplatin was associated with similar deterioration in nausea control across the study period, and similar impact on FLIE scores (see table ). Conclusions: Our results are consistent with the recommendation that A/C regimens be considered highly emetogenic, with similar impact on patient symptoms and quality of life compared with cisplatin. Delayed CINV remains a target for antiemetic intervention. Similar studies need to be repeated in patients receiving additional NK1 antagonists to assess their impact on CINV outside clinical trials. [Table: see text] [Table: see text]

Meta-Analysis of the Safety of 5-HT3 Antagonists with Dexamethasone or Droperidol for Prevention of PONV

Antiemetic guidelines recommend a combination of serotonin (5-HT3) with a second agent such as droperidol or dexamethasone. Physicians have been reluctant to employ these guidelines due to concerns over the black-box warning of droperidol and safety concerns with a steroid. To assess the safety profiles of 5-HT3 receptor antagonist (5-HT3RA) monotherapy and combination therapy with a steroid or droperidol for prophylaxis of postoperative nausea and vomiting (PONV). A MEDLINE search of English-language reports of randomized controlled trials (RCTs) was conducted (1966-September 2005) using the key terms 5-HT3, granisetron, ondansetron, dolasetron, tropisetron, PONV, postoperative, vomiting, emesis, and nausea. RCTs with treatment arms comparing 5-HT3RA monotherapy (granisetron, ondansetron, dolasetron, or tropisetron) with dexamethasone or droperidol or 5-HT3RA combinations and providing incidence data on adverse events were identified and reviewed. Within-study odds ratios with 95% confidence intervals were calculated to determine the incidence rates of all adverse events in RCTs using 5-HT3RA monotherapy and combination therapies. Overall effect sizes for frequently reported adverse events were estimated by pooling ORs using fixed- and random-effect models. Pooled ORs (OR(pooled)) for adverse events with 5-HT3RA/dexamethasone versus 5-HT3RA for PONV prophylaxis were not significant for any reported adverse events or the overall incidence of adverse events; 5-HT3RA/droperidol versus 5-HT3RA was significant only for decreased headache incidence (fixed model: OR(pooled) 0.35; 95% CI 0.18 to 0.69). The OR(pooled) for 5-HT3RA/dexamethasone versus dexamethasone was not significant for any reported adverse events except headaches (fixed model OR(pooled) 1.75; 95% CI 1.01 to 3.03), none of which was serious. OR(pooled) for 5-HT3RA/droperidol versus droperidol was not significant for any reported adverse events. Avascular necrosis, occult infection, and delayed wound healing were not observed with either combination therapy. Cardiac abnormalities were observed with 5-HT3RA/droperidol therapy. This meta-analysis indicates that either therapy has a safety profile similar to that of dexamethasone, droperidol, or 5-HT3RA.

Emerging drugs for chemotherapy-induced emesis

Chemotherapy-induced nausea and vomiting (CINV) is associated with a significant deterioration in quality of life. The emetogenicity of the chemotherapeutic agents, repeated chemotherapy cycles and patient risk factors (female gender, younger age, no alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a significant clinical problem. Two new agents, palonosetron and aprepitant, have recently been approved for the prevention of both acute and delayed CINV. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. Aprepitant is the first agent available in the new drug class of neurokinin-1 receptor (NK-1) antagonists. There are a number of 5-HT3 receptor antagonists and NK-1 receptor antagonists currently in Phase II and III clinical trials. Revised antiemetic guidelines for the prevention of CINV are reviewed. Future studies may consider the use of palonosetron and aprepitant with current and other new agents (olanzapine, gabapentin) in moderately and highly emetogenic chemotherapy, as well as in the clinical settings of multiple-day chemotherapy and bone marrow transplantation.

Employment of Substandard Antiemetic Prophylaxis in Recent Trials of Chemotherapy-Induced Nausea and Vomiting

To determine the prevalence of substandard antiemetic therapy among recently published trials conducted in patients with cancer who received emetogenic chemotherapy. A MEDLINE search was conducted (2000-July 2004) using the key words 5-HT(3) antagonists, ondansetron, granisetron, dolasetron, tropisetron, ramosetron, palonosetron, NK-1 antagonists, and aprepitant. All antiemetic trials in patients receiving chemotherapy that were published from January 2000 to July 2004 were evaluated. Standard prophylactic antiemetic therapy was derived from contemporary antiemetic guidelines published by oncology professional organizations and expert panels. The number of patients and studies in which patients received standard and substandard antiemetic therapy was determined for both the acute and delayed phases of chemotherapy-induced nausea and vomiting (CINV). Separate determinations were made for severely and moderately emetogenic chemotherapy. The annual percentage of studies in which substandard antiemetic prophylaxis was given and the percentage of patients who received substandard prophylaxis also were determined. Fifty-six studies were reviewed, which included a total of 10 274 patients and 125 study arms. The percentage of patients who received substandard antiemetic prophylaxis was 30% (n = 3063) for acute CINV and 33% (n = 3413) for delayed CINV. The average annual percentage of studies that employed substandard prophylaxis during this time period was 54%. In recent antiemetic trials for CINV, the employment of substandard antiemetic therapy is common. These results raise important ethical questions regarding contemporary antiemetic trial design.

Antiemetic therapy in cancer: an update

Although nausea and vomiting are widely recognised as two of the most distressing symptoms of cytotoxic therapy, there is still concern over the adequate control of these symptoms in the cancer population. Recently updated Antiemetic Consensus Guidelines recommend the prophylactic treatment of all patients at moderate-to-high risk of experiencing nausea and vomiting following chemotherapy and radiotherapy. It is important that these guidelines are fully adhered to; however, when considering which antiemetic regimen is most appropriate in an individual patient, it is also important to consider individual patient-related factors. In addition, certain patient groups, such as the young or the elderly, may be in need of specific consideration due to age-related factors that may influence treatment decisions.

Antiemetic guidelines: are they being used?

Evidence-based guidelines are regarded as therapeutic standards for many medical interventions. However, implementation of such recommendations seems to be rather difficult. An international antiemetic guideline for the treatment of patients undergoing chemotherapy was issued by the Multinational Association of Supportive Care in Cancer in 1997 and has been in use ever since. However, for many reasons, the guideline has not been followed completely, despite the fact that if antiemetics are used in accordance with guidelines, efficacy is similar to that achieved in randomised controlled trials. Structural difficulties, patients characteristics, and other barriers, such as the individual acceptance of guidelines and education of physicians and nurses, could be crucial factors for successful implementation. Thus, better adherence to antiemetic guidelines can only be achieved through a complex and long-term process, consisting of efficient education, training, and monitoring of all individuals involved.

The optimal dose of ondansetron as premedication for moderately or highly emetogenic chemotherapy

8209 Background: Anti-emetic guidelines recommend the use of a serotonin-receptor antagonist for the prevention of acute emesis prior to the administration of highly or moderately emetogenic chemotherapy. However, dosages of these agents, such as ondansetron, vary throughout the literature. Our trial was undertaken to determine the optimal dosage of ondansetron in terms of anti-emetic efficacy and safety while keeping in mind a cost-conserving perspective. Methods: In this single institution study, all patients scheduled to receive moderately or highly emetogenic chemotherapy (Hesketh criteria ≥ 3) in a six month period for various cancer types were eligible. Ondansetron 32mg I.V. was administered prior to the first cycle of chemotherapy. De-escalation of the dosage to 24mg and 16mg I.V. occurred with cycles two and three, respectively. Acceptable response was defined as no emesis or mild nausea. Failure was defined as ≥1 episodes of emesis or nausea lasting more than 30 minutes. Efficacy and side effects were monitored for 24 hrs. McNemar test for repeated measures was used to compare dosage responses. Results: A total of 52 patients were properly enrolled. 35 patients received a Hesketh 5 regimen, 16 patients received a Hesketh 4 regimen, and 1 patient received a Hesketh 3 regimen. Acceptable response rates were 86.5% in the 32mg group, 78.8% in the 24mg group, and 63.5% in the 16mg group. When we compared the 32mg vs. the 24mg group in terms of acceptable versus failed response there was no statistical difference (p= 0.22). However, statistical differences were significant when comparing the 24mg vs. the 16mg group (p=0.02) and the 32mg vs. the 16mg group (p=0.001). All three doses of ondansetron were well tolerated with no unexpected drug-related adverse effects. Headache was the most commonly reported side effect and occurred in 23% of the patients. Conclusions: Despite our small sample size, differences in efficacy became apparent once the dosage was de-escalated below 24mg. Although lower dosages are more cost efficient, 24mg should be the minimal dosage of ondansetron administered prior to moderately or highly emetogenic chemotherapy. No significant financial relationships to disclose.

Study of the effect of standardized chemotherapy order forms on prescribing errors and anti-emetic cost

Many anti-neoplastic medication errors and excessive use of serotonin antagonist anti-emetic agents might be prevented by the use of a standardized chemotherapy order form (SCOF). Several studies showing a reduction in prescribing errors or control of inappropriate anti-emetic use through the use of SCOFs have been reported. No previously published study reported SCOFs were used to reduce both prescribing errors and anti-emetic cost. This study attempts to measure these outcomes in a haematology-oncology pharmacy service. The study consisted of a four-month control period, followed by a four-month test period following dissemination of the standardized order forms. In each period, prescriber errors and anti-emetic use were monitored. During the control period, using clinical studies from the primary literature and anti-emetic guidelines, 64 SCOFs representing the most commonly used chemotherapy regimens in the medical oncology and gynaecology oncology services were developed by the haematology-oncology pharmacy. Differences in prescribing error rate and anti-emetic cost were compared between each period and with the institution's historic prescribing error rate. During the control period, 1078 orders for oral and parenteral granisetron and ondansetron with combined total acquisition cost of $76 454.64 and a mean cost of $70.92 were dispensed. During the test period, the pharmacy dispensed 1121 orders with an acquisition cost of $73 331.61 and a mean cost of $65.42. A savings of $3123.03 resulted from a reduction of the amount prescribed in the test period. The difference in mean cost per order between the two periods was significant (P <0.037). Fifty-three prescribing errors out of 3592 medication orders were detected in the control period, while 12 errors out of 3585 medication orders were detected during the test period. A significant difference(P <0.0001) was detected between the two periods. There was a significant difference (P <0.0001) between the control period and the institution's historic prescribing error rate and no difference between the test period and the institution's historic prescribing error rate. SCOFs significantly reduced serotonin antagonist anti-emetic cost and prescribing error rate over a four-month period.

Radiotherapy-induced nausea and vomiting (RINV): antiemetic guidelines

As many as 40-80% of patients undergoing radiotherapy (RT) will experience nausea and/or vomiting, depending on the site of irradiation. Fractionated RT may involve up to 40 fractions over a 6-8 weeks period, and prolonged symptoms of nausea and vomiting could affect quality of life. Furthermore, uncontrolled nausea and vomiting may result in patients delaying or refusing further radiotherapy. Nausea and vomiting are often underestimated by radiation oncologists. Incidence and severity of nausea and vomiting depend on RT-related factors (single and total dose, fractionation, irradiated volume, radiotherapy techniques) and patient-related factors (gender, general health of the patient, age, concurrent or recent chemotherapy, psychological state, tumor stage). Current antiemetic guidelines prescribe the emetogenicity of radiotherapy regimens and recommend the use of 5-HT(3) antagonists with or without a steroid for prophylaxis in moderately and highly emetogenic treatment (MASCC, ASCO, ASHP, NCCN). The new proposed guidelines summarise the updated data from the literature and take into consideration the existing guidelines. According to the irradiated area (the most frequently studied risk factor), the proposed guidelines are divided into four levels of emetogenic risk: high, moderate, low and minimal. They offer guidance to prescribing physicians for effective antiemetic therapies in RINV.

Chemotherapy-induced nausea and vomiting: current and new standards in the antiemetic prophylaxis and treatment

Nausea and vomiting are considered as two of the most distressing side-effects of chemotherapy. Chemotherapy-induced nausea and vomiting have been classified into acute, delayed and anticipatory based on the time of onset. The frequency of nausea and vomiting depends primarily on the emetogenic potential of the chemotherapeutic agents used. With the introduction of the 5-HT 3 receptor-antagonists in combination with dexamethasone in the early 1990s approximately 70% of patients receiving highly emetogenic chemotherapy were protected from acute emesis. However, 40% of patients have symptoms in the delayed phase. Another group of antiemetics, the neurokinin-1-receptor-antagonists, have recently been introduced. The addition of neurokinin receptor (NK1 receptor)-antagonists to standard therapy significantly improves emesis protection in the acute and in particular in the delayed phase by approximately 20%. Due to these new developments, revised antiemetic guidelines have been set. Here, the most recent developments in antiemetic therapy, including these guidelines, are reviewed.

Patient expectation is a strong predictor of severe nausea after chemotherapy

Patients may use their past experiences with nausea, as well as information about the incidence of nausea from chemotherapy that other patients have experienced, to form a prediction, or response expectancy, of nausea from their own upcoming chemotherapy. Mounting evidence suggests that these expectancies relating to nausea are significant predictors, and, likely, contributing factors to the development of treatment-related nausea. The patients in the current study were participants in the control arm of a multicenter clinical trial conducted between November 1999 and July 2001 by the University of Rochester Community Clinical Oncology Program. All patients in the current report were age >/= 18 years and were about to begin a first cancer treatment regimen containing doxorubicin. Expectancy of nausea assessed before patients received their first doxorubicin-based chemotherapy treatment was found to be a strong predictor of subsequent nausea and in fact was stronger than previously reported predictive factors, including age, nausea during pregnancy, and susceptibility to motion sickness. Women who believed it was "very likely" that they would have severe nausea from chemotherapy were five times more likely to experience severe nausea than fellow patients who thought its occurrence would be "very unlikely." Further studies confirming an expectancy of nausea as a risk factor are warranted as are studies examining the benefit to a patient's quality of life from modifying antiemetic treatment guidelines to take into account symptom expectancies. Finally, ethically acceptable interventions that are designed to reduce patients' nausea expectancies or increase their expectancies of nausea control should be developed and studied.

Antiemetic efficacy of selective serotonin receptor (5HT3) antagonist, granisetron, on delayed chemotherapy-induced nausea and vomiting (CINV) in CPT-11 and 5-FU based chemotherapy (CT)

8187 Background: Though significant advances have been made in cancer treatment, CINV still remains significant patients (pts) concerns. Antiemetic guidelines based on emesis rate category have been proposed for the prevention of CINV (Support Care Cancer 2002; 10: 519–22). Dexamethasone (Dex) and 5HT3 antagonist are recommended for the prevention of acute and delayed CINV of CT using high emesis category drugs. However, there is no standard recommendation for delayed CINV of moderate emesis category drugs, such as CPT-11. The efficacy of granisetron, 5HT3 antagonist, on delayed CINV after CPT-11 and 5-FU based CT was investigated. Methods: Pts who had a delayed CINV were eligible for the study. Treatment regimen was consisted of a 90-min infusion of CPT-11 150mg/m2 on day 1 and 15, and UFT 375mg/m2/day on days 3–7, 10–14, 17–21 and 24–28, q5w. All pts received intravenous betamethasone and granisetron for prophylaxis against acute emesis on the day of CPT-11 administration. When pts had delayed CINV, 2 mg of granisetron was orally administered on days 2–6, and 16–20 of next treatment cycle. The severity of their gastrointestinal symptoms (anorexia, nausea, vomiting) on days 2–7, and 16–21 was recorded every day according to NCI-CTC, and pts preference of this treatment was recorded using questionnaire on days 8 and 22. The efficacy of the treatment was assessed in each patient by the comparison of severity of CINV with or without oral granisetron. Results: 16 pts (53.3%) of 30 pts who had received the CT had delayed CINV. The incidence of grade 2 or more vomiting was significantly greater in female than in male pts (54.6% vs 32.1%, p=0.002). Although granisetron did not improve the overall incidence of anorexia, nausea, and vomiting, the incidence of grade 2 or more vomiting in female pts was significantly reduced by granisetron (54.6% vs 32.4%, p=0.001). The questionnaire on pts preference revealed 76% of pts had preference for the treatment. Conclusions: Oral administration of granisetron for prevention against delayed CINV might be effective in female pts. No significant financial relationships to disclose.

Antiemetic efficacy of selective serotonin receptor (5HT3) antagonist, granisetron, on delayed chemotherapy-induced nausea and vomiting (CINV) in CPT-11 and 5-FU based chemotherapy (CT)

8187 Background: Though significant advances have been made in cancer treatment, CINV still remains significant patients (pts) concerns. Antiemetic guidelines based on emesis rate category have bee...

Nausea: the neglected symptom?

Advances in antiemetic therapy over the past decade have undoubtedly eased the burden of radiotherapy- and chemotherapy-induced nausea and vomiting. Despite this, these distressing side-effects of cancer therapy are still experienced by some patients. Moreover, nausea has both a higher incidence and a greater effect on patient quality of life than vomiting. The impact of nausea may therefore warrant more attention than perhaps it has received previously, and there is undoubtedly room for improvement regarding its treatment. Recognizing and treating nausea is complicated by the fact that it can only be measured subjectively by the patient rather than objectively by clinical staff. However, various patient-centred strategies may be employed by nurses to ensure self-reporting of the occurrence and impact of nausea. Nurses may also be best placed to identify patient-related prognostic factors in order to determine the risk of nausea. Antiemetic guidelines recommend the use of a 5-HT 3-receptor antagonist for the control of emesis with moderate and highly emetogenic cancer therapy. Although guidelines do not distinguish between the available agents, pharmacological differences do exist, and it is necessary to consider this when tailoring regimens to individual patients. As with any therapy, less complicated dosing regimens are likely to improve compliance, an issue that may be particularly pertinent in nauseated patients who are unable to ingest multiple doses. Furthermore, the focus of antiemetic therapy should be on prevention, as the presence and severity of acute symptoms have been linked to occurrence of symptoms in the delayed phase and the likelihood of anticipatory nausea and vomiting with further treatment cycles. This review aims to assess the potentially neglected symptom of nausea and focuses on recognizing and controlling this side-effect of cancer therapy.

Same Old Story? Do We Need to Modify Our Supportive Care Treatment of Elderly Cancer Patients? Focus on Antiemetics

The incidence of cancer is highest among individuals > or =65 years of age. Physiological changes associated with aging, such as cognitive decline, renal and hepatic dysfunction, can often complicate treatment options, and the elderly represent a particular challenge to the oncologist because of the high incidence of comorbidity and polypharmacy. Effective supportive care is of particular importance in elderly cancer patients as they may recover less satisfactorily if adverse events are poorly controlled. Nevertheless, evidence suggests that supportive care agents, for example, antiemetics, are underutilised in this patient population. Chemotherapy and radiotherapy regimens are frequently associated with nausea and vomiting--symptoms that can have deleterious effects on vulnerable patients if not adequately managed. The serotonin 5-HT3-receptor antagonists represent a class of antiemetics that are currently regarded as the gold standard treatment for chemotherapy- and radiotherapy-induced nausea and vomiting. They are recommended as first-line treatment for patients at moderate-to-high risk of emesis. However, antiemetic guidelines do not differentiate between these agents and, more importantly, do not contain specific recommendations for the elderly. Pharmacological differences exist between the commonly available 5-HT3-receptor antagonists (dolasetron, granisetron, ondansetron, tropisetron and palonosetron), namely receptor sensitivity, duration of action, metabolism and tolerability profile. Of particular concern with prescriptions to elderly cancer patients is the convenience of once-daily administration, the low potential for drug-drug interactions and cardiovascular adverse effect profile. Moreover, the addition of the newly approved neurokinin NK1-receptor antagonist aprepitant to the choice of antiemetic regimen may complicate therapy and exacerbate the drug-drug interaction risk in elderly patients. Therefore, the use of antiemetics that are well tolerated and with the lowest risk of drug-drug interactions is imperative in this patient population and will enable even those patients with several comorbidities and a high level of polypharmacy to receive effective antiemetic therapy.

Antiemetic prescription in Italian breast cancer patients submitted to adjuvant chemotherapy

The aim of this study was to investigate if the Multinational Association of Supportive Care in Cancer (MASCC) antiemetic guidelines for the prevention of both acute and delayed emesis induced by highly-moderately emetogenic chemotherapy were transferred in daily clinical practice in Italy 2 years after their publication. From 16 to 23 March 2000, all consecutive breast cancer patients referred to 87 Italian oncological centers to receive any cycle of adjuvant chemotherapy were monitored. Of 715 evaluable patients submitted to chemotherapy, 533 received cyclophosphamide, methotrexate, 5-fluorouracil (CMF) and 151 anthracyclines. Patients receiving taxanes or other experimental therapies (31) were not considered. The MASCC-recommended antiemetic prophylaxis against acute/delayed emesis was prescribed in 56.3/45.9% patients. Antiemetic prophylaxis against delayed emesis was not prescribed to 30.6% of patients. The MASCC-recommended prescription against acute emesis was more frequently followed in research centers, in Northern Italy, and in centers with experience on antiemetic research. Two years after the publication of the MASCC antiemetic guidelines, strong discrepancies between these and antiemetic prescriptions in daily clinical practice in Italy were observed. The similarity of these results with those obtained in our previous drug utilization study on antiemetics, carried out before the publication of the MASCC guidelines, leads us to conclude that the transferability of antiemetic guidelines to daily clinical practice in Italy has been modest. A great effort should be made in Italy by the National Health Service to accelerate the process of implementation of antiemetic guidelines.

Chemotherapy-Induced Delayed Emesis: What is the Role of 5-HT3Antagonists?

Objective: To review the current literature assessing the efficacy of different antiemetics, with a focus on comparison between serotonin (5-HT3) antagonists and other antiemetics, in the treatment of delayed emesis induced by either cisplatin or non-cisplatin cytotoxic agents. Data Sources: A MEDLINE search (1966–July 2002) was performed using delayed emesis, vomiting, nausea, chemotherapy, cisplatin, moderately emetogenic, selective serotonin subtype-3 (5-HT3) receptor antagonists, metoclopramide, domperidone, corticosteroids, dexamethasone, prognostic factors, risk factors, and neurokinin-1 (NK1) receptor antagonists as key words or subject headings. Only English-language articles were identified and included. Additional references were retrieved from selected articles. Data Synthesis: Various antiemetic consensus guidelines have recommended the use of different pharmacologic treatment, including the use of 5-HT3 antagonists, for the prevention of chemotherapy-induced delayed emesis. In some instances, it has been suggested that combinations containing a 5-HT3 antagonist may be superior to others. Current data have been synthesized in an attempt to demonstrate the efficacy of 5-HT3 antagonists in the treatment of chemotherapy-induced delayed emesis. Conclusions: Dexamethasone has consistently shown its antiemetic efficacy for delayed emesis induced by cisplatin and non-cisplatin agents, whereas the role of 5-HT3 antagonists alone remains controversial. Metoclopramide has been shown to be as efficacious as 5-HT3 antagonists when combined with dexamethasone for the prevention of delayed emesis. As a result, 5-HT3 antagonists should be reserved as second-line agents to metoclopramide in addition to dexamethasone. NK1 receptor antagonists have shown some early promising results. However, many questions need to be addressed before their extensive use in clinical practice.

Chemotherapy-induced nausea and vomiting: the importance of acute antiemetic control.

Nausea and vomiting are two of the most feared side effects of cancer chemotherapy and radiotherapy. Chemotherapy-induced nausea and vomiting can be broadly categorized as acute (occurring within 24 hours of therapy), delayed (persisting for 6-7 days after therapy), or anticipatory (occurring prior to chemotherapy administration). Breakthrough and refractory nausea and vomiting describe the symptoms of uncontrolled emesis. Evidence suggests that good control of nausea and vomiting during the acute period correlates with the control of delayed emesis. Conversely, protection failure during the first 24 hours has a high predictive value for delayed emesis in the same cycle. The 5-HT(3)-receptor antagonists, regarded as the 'gold standard' in antiemetic therapy, are the first-line treatment for moderately and highly emetogenic chemotherapy and radiotherapy regimens in adults and children. Evidence suggests that the 5-HT(3)-receptor antagonists administered in combination with corticosteroids afford the best protection from symptoms of acute emesis and, by extrapolation, the most effective prevention of delayed emesis. Antiemetic therapeutic guidelines stress that the goal of therapy is to prevent cytostatic-induced nausea and vomiting. Therefore, the prophylactic use of the most effective antiemetic regimen-taking into consideration the emetogenicity of the chemotherapy and individual patient characteristics-must be adhered to in order to prevent acute, delayed, and anticipatory nausea and vomiting.