Prevention of chemotherapy- and radiotherapy-induced emesis: Results of the Perugia Consensus Conference

Background: The need to review and summarize the evidence concerning preventive treatment of cancer chemotherapy- and radiotherapy-induced emesis.Design: After a survey among experts the Antiemetic Subcommittee of the MASCC planned and held a Consensus Conference on antiemetic therapy. Recommendations were provided on the basis of scientific confidence and the level of consensus among the participating experts.Results and conclusions: A 5-HT₃ antagonist plus dexamethasone is the regimen of choice in the prevention of acute emesis induced by single high, and low and repeated doses of cisplatin, and of acute emesis induced by moderately-high emetogenic chemotherapy (i.e., cyclophosphamide, doxorubicin, epirubicin, carboplatin, used alone or in combination) in both adults and children.In the prevention of delayed emesis induced by cisplatin the most efficacious choice is a combination of dexamethasone with either metoclopramide or a 5-HT₃ antagonist, while in moderately-high emetogenic chemotherapy dexamethasone alone or a 5-HT₃ antagonist alone or their combination should be used. No evidence or consensus exists regarding antiemetic treatment for patients receiving low emetogenic chemotherapy, or about the optimal rescue treatment for patients failing antiemetic prophylaxis. The best treatment for anticipatory emesis is the best possible control of acute and delayed emesis.Although 5-HT₃ antagonists have some efficacy in the prevention of acute emesis induced by high-dose chemotherapy, more studies should be carried out to determine the best preventive treatment. For prevention of acute emesis induced by highly/moderately emetogenic radiotherapy (TBI, irradiation of the upper part of the abdomen or of the whole abdomen/radiotherapy of the thorax, pelvis and lower body half) a 5-HT₃ antagonist is the best choice.     

The Effect of Ondansetron on Radiation-Induced Emesis and Diarrhoea

Fractionated radiotherapy of malignancies in the abdomen induces nausea and vomiting in approximately 50% of the patients. During abdominal irradiation the damaged gastrointestinal mucosa releases 5-HT with ensuing activation of 5-HT₃ receptors which may explain the nausea and vomiting. Ondansetron is a new 5-HT₃-antagonist with antiemetic properties. In this consecutive study, 33 patients receiving fractionated upper abdominal irradiation (100 cm², 1, 8-4 Gy daily dose for a mean of 13 days) were treated with ondansetron (8 mg t.d.s. p.o.). Emesis was completely controlled in 26/33 (79%) patients throughout their radiation course, which embraced 628 (94%) treatment days. Ondansetron was well tolerated. Eleven patients developed mild constipation. No patients experienced diarrhoea (a common distressing side-effect of abdominal irradiation). It is suggested that ondansetron can be of value in preventing emesis in patients receiving fractionated radiotherapy. The possible beneficial effect in preventing diarrhoea must be further evaluated.     

Antiemetic control with palonosetron in patients with gastrointestinal cancer receiving a fluoropyrimidine-based regimen in addition to either irinotecan or oxaliplatin: a retrospective study

Background: For moderately emetogenic chemotherapy, palonosetron (PALO) is reported to provide complete control of chemotherapy-induced nausea and vomiting (CINV) in 69% of patients. Prior to August 2009, our gastrointestinal (GI) cancer patients receiving the moderately emetogenic compounds oxaliplatin or irinotecan plus a fluoropyrimidine regimen received ondansetron and dexamethasone orally on day 1 of chemotherapy for CINV prevention. Beginning in August of 2009, ondansetron was replaced by PALO 0.25 mg (intravenous push). Methods: This is a single-institution retrospective study of GI cancer patients who received oxaliplatin or irinotecan plus a fluoropyrimidine. Failure of an antiemetic regimen was defined as grade ≥1 vomiting or grade ≥2 nausea (Common Terminology Criteria for Adverse Events, version 3) on days 1 through 5 following chemotherapy. Patients were divided for analysis into pre-PALO and post-PALO cohorts. Fisher's exact test compared cohort differences. Results: A total of 305 patients were included in the study, with 157 patients in the pre-PALO cohort and 148 in the post-PALO cohort. For all patients, the risk of antiemetic failure was reduced from 50.3% [95% confidence interval (CI) 42.2-58.4%] to 28.4% (95% CI 21.3-36.4%) with PALO. This reduction in the relative risk of antiemetic failure was observed in all subgroups. Conclusion: The addition of PALO may provide increased control of CINV for the moderately emetogenic regimens of oxaliplatin or irinotecan plus a fluoropyrimidine in GI cancer patients.     

Practice Patterns for Prevention of Chemotherapy-Induced Nausea and Vomiting and Antiemetic Guideline Adherence Based on Real-World Prescribing Data

BackgroundGuideline‐recommended antiemetic prophylaxis improves nausea and vomiting control in most patients undergoing chemotherapy. Multinational Association of Supportive Care in Cancer/European Society for Medical Oncology (MASCC/ESMO) antiemetic guidelines recommend prophylaxis with a neurokinin‐1 receptor antagonist (NK₁RA), a 5‐hydroxytryptamine‐3 receptor antagonist (5‐HT₃RA), and dexamethasone for patients receiving highly emetogenic chemotherapy (HEC), including anthracycline‐cyclophosphamide (AC)‐ and carboplatin (considered moderately emetogenic chemotherapy)‐based chemotherapy. Here, we analyze the use of NK₁RA–5‐HT₃RA–dexamethasone for antiemetic prophylaxis associated with HEC and carboplatin.MethodsThe data source was the Global Oncology Monitor (Ipsos Healthcare). Geographically representative physicians from France, Germany, Italy, Spain, and the U.K. were screened for treatment involvement and number of patients treated per month. Patients’ data from January to December 2018 were collected from medical charts and extrapolated on the basis of the total number of physicians who prescribe chemotherapy. The emetic risk of chemotherapy was classified per MASCC/ESMO guidelines.ResultsData from 45,324 chemotherapy‐treated patients were collected, representing a total extrapolated prevalence of 1,394,848 chemotherapy treatments included in the analysis. NK₁RAs were used in 45%, 42%, and 19% of patients receiving cisplatin‐, AC‐, and carboplatin‐based chemotherapy, respectively; 18%, 24%, and 7% received the guideline‐recommended NK₁RA–5‐HT₃RA–dexamethasone combination; no antiemetics were prescribed for 12% of the treatments. Often, physicians’ perception of the emetic risk of chemotherapy did not follow MASCC/ESMO guideline classification.ConclusionLow adherence to antiemetic guidelines was revealed in clinical practice in five European countries, with 15% of all HEC‐/carboplatin‐based treatments receiving guideline‐recommended NK₁RA–5‐HT₃RA–dexamethasone prophylaxis and 12% of them receiving no antiemetics. New strategies for improving guideline adherence are urgently needed.Implications for PracticeDespite recent advances in antiemetic therapy, a substantial proportion of patients experience nausea and vomiting associated with chemotherapy in daily clinical practice. Antiemetic guidelines aim at prevention of chemotherapy‐induced nausea and vomiting (CINV), and guideline‐consistent antiemetic therapy can effectively prevent vomiting and, to a lesser extent, nausea in most patients with cancer. This study reports low adherence to antiemetic guidelines in the highly emetogenic chemotherapy setting in daily clinical practice across five European countries. Opportunity exists to increase adherence to antiemetic guideline recommendations. Implementation of strategies to facilitate guideline adherence can potentially improve CINV control.     

Prevention of delayed chemotherapy-induced nausea and vomiting after moderately high to highly emetogenic chemotherapy: comparison of ondansetron, prochlorperazine, and dexamethasone

The purpose of this article is to assess the comparative antiemetic efficacy of prochlorperazine, ondansetron, and dexamethasone in the prevention of delayed chemotherapy-induced nausea and vomiting (CINV) after moderately high to highly emetogenic chemotherapy. Cancer patients (n = 232) receiving moderately high to highly emetogenic chemotherapy were randomized to 1 of 3 treatments: 15 mg prochlorperazine spansules twice daily; 8 mg ondansetron tablets twice daily; or 8 mg dexamethasone tablets twice daily on days 2 through 5. All patients received 24 mg ondansetron and 20 mg dexamethasone orally before chemotherapy. Daily assessment (days 1 through 5) included the number of episodes of retching and vomiting, severity of nausea, restlessness, difficulty concentrating and fatigue, treatment satisfaction, and overall quality of life (measured using a 10-cm VAS). The Functional Living Index-Emesis (FLIE) was completed on day 5. Other side effects attributed to antiemetic therapy were recorded daily. For acute CINV, total control, defined as no vomiting, retching, nausea <1 cm on a 10-cm visual analog scale, and no administration of rescue medications, was achieved in 78% in the overall group and was not significantly different in the patients randomized to the 3 treatment arms for delayed CINV. Delayed CINV was reported by 43% to 57% of patients, with the highest incidence reported on day 3. For delayed CINV, patients receiving prochlorperazine reported the lowest average nausea score on days 2 to 5, whereas patients receiving ondansetron reported the highest nausea score (P = 0.05). No statistically significant differences in CINV or side effects of antiemetic therapy were noted between treatment groups on days 2 to 5. For patients similar to those included in this study, there does not appear to be a clinically important difference in efficacy, adverse effects, or treatment satisfaction among dexamethasone, prochlorperazine, and ondansetron in the doses used in these delayed CINV regimens on days 2 to 5 in this study.     

Ondansetron versus metoclopramide in the prevention of chemotherapy-induced nausea and vomiting - a metaanalysis

Nausea and vomiting remain important clinical problems occuring in 25 to 50% of patients receiving chemotherapy for cancer. Clinical trials comparing a new antiemetic drug, ondansetron, to metoclopramide have suggested improved control of nausea and vomiting but studies disagree on the magnitude of the treatment effect and its statistical significance. We combined evidence from randomized controlled trials in a meta-analysis of the efficacy and safety of ondansetron compared to metoclopramide in the prevention of acute (less-than-or-equal-to 24 hours) nausea and emesis associated with chemotherapy. Literature search identified six randomised controlled trials of ondansetron versus metoclopramide in an adult population. Study outcomes were the observed incidence of emesis (vomiting or retching) and patient-reponed grades of nausea after chemotherapy. For meta-analysis of each outcome we defined therapeutic success as complete protection (ie. zero episodes during 24 hours following chemotherapy). The relative odds of success (ondansetron/metoclopramide) was calculated for each trial and all trials combined. Results were expressed as a relative risk (RR) for zero emesis or nausea at 24 hours. The six trials reported on 705 patients (median age range 53-59 years; 57% female). Relative odds for complete control of emesis was greater than one in all trials but was nonsignificant (p>0.05) in two trials, including the largest trial. When trials were combined, summary odds ratios for control of emesis and nausea were greater than one (p<0.05). RR of zero emesis with ondansetron was 1.72 (95% CI 1.45 to 1.97) and was similar for nausea (RR= 1.78, 95% CI 1.39 to 2.13). In trials using high-dose cisplatin chemotherapy, higher rates of extrapyramidal affects and diarrhea were associated with metoclopramide (p<0.05) while headache was frequently associated with ondansetron (p<0.05). Combined clinical trial evidence supports the conclusion. that, relative to metoclopramide, ondansetron places patients at a much lower risk of nausea and emesis following chemotherapy with moderately or highly emetogenic regimens.     

The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin--the Aprepitant Protocol 052 Study Group.

PURPOSE: In early clinical trials with patients receiving highly emetogenic chemotherapy, the neurokinin antagonist aprepitant significantly enhanced the efficacy of a standard antiemetic regimen consisting of a type-three 5-hydroxytryptamine antagonist and a corticosteroid. This multicenter, randomized, double-blind, placebo-controlled phase III study was performed to establish definitively the superiority of the aprepitant regimen versus standard therapy in the prevention of chemotherapy-induced nausea and vomiting (CINV). PATIENTS AND METHODS: Patients receiving cisplatin > or = 70 mg/m2 for the first time were given either standard therapy (ondansetron and dexamethasone on day 1; dexamethasone on days 2 to 4) or an aprepitant regimen (aprepitant plus ondansetron and dexamethasone on day 1; aprepitant and dexamethasone on days 2 to 3; dexamethasone on day 4). Patients recorded nausea and vomiting episodes in a diary. The primary end point was complete response (no emesis and no rescue therapy) on days 1 to 5 postcisplatin, analyzed by a modified intent-to-treat approach. Treatment comparisons were made using logistic regression models. Tolerability was assessed by reported adverse events and physical and laboratory assessments. RESULTS: The percentage of patients with complete response on days 1 to 5 was significantly higher in the aprepitant group (72.7% [n = 260] v 52.3% in the standard therapy group [n = 260]), as were the percentages on day 1, and especially on days 2 to 5 (P <.001 for all three comparisons). CONCLUSION: Compared with standard dual therapy, addition of aprepitant was generally well tolerated and provided consistently superior protection against CINV in patients receiving highly emetogenic cisplatin-based chemotherapy.     

Palonosetron: a second-generation 5-hydroxytryptamine receptor antagonist

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, alcohol consumption, history of motion sickness) are the major risk factors for CINV. The use of 5-hydroxytryptamine (5-HT)3 receptor antagonists plus dexamethasone has significantly improved the control of acute CINV, but delayed nausea and vomiting remains a clinical problem. A new agent, palonosetron, has recently been approved for the prevention of acute CINV in patients receiving either moderately or highly emetogenic chemotherapy and for the prevention of delayed CINV in patients receiving moderately emetogenic chemotherapy. Palonosetron is a 5-HT3 receptor antagonist with a longer half-life and a higher binding affinity than first-generation 5-HT3 receptor antagonists. In a single dosing study, palonosetron was highly effective in controlling CINV compared with a single dose of dolasetron or ondansetron in patients receiving moderately emetogenic chemotherapy. Palonosetron in combination with dexamethasone demonstrated control of CINV in patients receiving highly emetogenic chemotherapy. Palonosetron appeared to be as effective in subsequent courses of chemotherapy compared with the initial course of chemotherapy. There were no clinically relevant differences seen among palonosetron, ondansetron or dolasetron in laboratory, electrocardiographic or vital-sign changes, and adverse reactions reported in the clinical trials were the most common reactions reported for the 5-HT3 receptor antagonist class. Recent studies using palonosetron-based anti-emetic combinations in moderately and highly emetogenic chemotherapy, as well as in the clinical setting of multiple-day chemotherapy, have been reported. Future studies may consider the use of palonosetron with current and other new agents and in other clinical settings, such as bone marrow transplantation and radiation therapy.     

Costs of treating and preventing nausea and vomiting in patients receiving chemotherapy.

PURPOSE: To evaluate the effect of ondansetron availability on the costs of managing nausea and vomiting. METHODS: We retrospectively assessed antiemetic costs (drug costs, nursing time, pharmacy time, physician's time, supplies, and facility "hotel" costs, in 1991 Canadian dollars) for all patients who received moderately or highly emetogenic chemotherapy from 6 months before to 6 months after ondansetron became commercially available in September 1991. We compared the costs for treating patients who received ondansetron versus those who received other antiemetic regimens, the costs for treating patients in the 6 months before versus the 6 months after ondansetron commercial availability, and the costs for treating patients in the first 4 months versus the last 4 months of the study period. RESULTS: We found no cost differences for patients treated with ondansetron versus other antiemetic regimens. However, there was a significant reduction in emesis management costs for patients treated after versus before the availability of ondansetron: for patients treated in the last third versus first third of the study period, there was a decrease in cost per patient per month of treatment of $374 (95% confidence interval, $243 to $505). These savings were achieved through a reduction in hospital bed days and other costs associated with the prevention and more effective management of nausea and vomiting. At the same time, the number of patients who received emetogenic chemotherapy and their average age increased, presumably because of the better control of gastrointestinal toxicity. CONCLUSION: Ondansetron availability has been associated with changes in the clinical management of cancer patients receiving chemotherapy and with overall cost savings compared with previously available antiemetic therapy.     

Antiemetic efficacy of an oral suspension of granisetron plus dexamethasone and influence of quality of life on risk for nausea and vomiting

OBJECTIVES: To assess the antiemetic efficacy of an oral suspension of granisetron/dexamethasone in patients receiving chemotherapy and to determine whether quality-of-life parameters influence the risk for postchemotherapy nausea and vomiting (PCNV). PATIENTS AND METHODS: In an open monocentric study, an oral suspension containing 2 mg granisetron and 16 mg (4 mg for moderately emetogenic chemotherapy) dexamethasone was administered to 43 chemotherapy-naive patients before highly (n = 16) or moderately (n = 27) emetogenic chemotherapy and on the 3 subsequent days (2 for moderately emetogenic chemotherapy). Emetic episodes were recorded and quality of life was assessed prior to each cycle with a questionnaire based on EORTC QLQ-30. RESULTS: In the group undergoing highly (moderately) emetogenic chemotherapy, complete control of acute vomiting was achieved in 60-72.7% (92.6-95.0%), and complete control of delayed vomiting in 37.5-40.0% (75.0-92.2%), of patients within the first 3 (5) cycles. The following quality-of-life parameters were significantly associated with PCNV: tiredness (RR = 1.3, p < 0.05), pain (RR = 1.5), impairment of daily life by pain (RR = 1.7), sensation of abdominal pressure and fullness (RR = 2.5), impairment of social activities (RR = 2.9). CONCLUSIONS: Once-daily oral administration of a suspension of granisetron/dexamethasone is an active prophylaxis of nausea and vomiting and compares favorably with data reported on intravenous administration. Quality-of-life parameters assessed pre-treatment could help to identify patients at high risk for nausea and vomiting so that antiemetic therapy can be tailored to individual patient risk.     

Results of a Double Blind Placebo Controlled Study of Ondansetron as an Antiemetic During Total Body Irradiation in Patients Undergoing Bone Marrow Transplantation

Total body irradiation (TBI) is a highly emetogenic component of the majority of conditioning regimens in use for bone marrow transplantation. Conventional antiemetic therapy fails to control nausea and vomiting induced by single fraction TBI in as many as 50% of patients. In a double blind study of 20 patients undergoing marrow transplantation, a single 8 mg ondansetron dose was compared with placebo given immediately prior to TBI. Our routine premedication of phenobarbitone and corticosteroid was also administered to all patients. All patients had received high dose melphalan the previous evening. Only 1 of the 10 patients in the ondansetron group experienced an emetic event compared with 5 of the 10 in the comparison group (p = 0.029). No significant adverse events were observed. Ondansetron appears to have extremely useful antiemetic activity during single fraction low dose rate TBI.     

Aprepitant: a substance P antagonist for chemotherapy induced nausea and vomiting

The episodes of nausea and vomiting which follow each cycle of chemotherapy are the most troublesome side effect experienced by cancer patients. Introduction of ondansetron was a definite therapeutic advance in treating chemotherapy induced nausea and vomiting (CINV) with more effectiveness with corticosteroids. However, the protection remained largely limited to acute phase of CINV with little or no effect over delayed phase. Aprepitant, a drug that antagonizes the effect of substance P on neurokinin type 1 receptor showed promising results in controlling both phases of CINV. This drug is well absorbed orally with a t max of about four hours. The addition of aprepitant to ondansetron and dexamethasone was found to be superior to ondansetron and dexamethasone alone in clinical trials with patients taking high and moderate emetogenic chemotherapy. This drug also showed a good safety profile, but its inhibitory effect on CYP3A4 may result in clinically significant drug interactions needing dose modifications of co-administered drugs. The National Comprehensive Cancer Network guidelines for CINV recommends the use of aprepitant with high and moderately emetogenic anticancer drugs. Results of ongoing clinical trials with aprepitant and other agents of this new class of antiemetics are awaited and may alleviate the sufferings of cancer patients.     

Ondansetron and dexamethasone in middle ear procedures

A randomised, double-blind study was conducted on 90 ASA I & II patients undergoing middle ear surgery to compare the efficacy of ondansetron, dexamethasone and a combination of Ondansett on+dexamethasone for the prevention of postoperative nausea and vomiting. Group I patients received ondansetron (0. 1 mg/kg), group IIpatients received dexamethasone(0.1z mg./Kg) while group III received ondansetron (0.1 mg./kg) + dexamethasone (0.15 mg/kg), 10 minute before induction of general anaesthesia. A standardised general anaesthetic technique was employed through out. A complete response, defined as no postoperative nausea and vomiting and no need for another rescue antiemetic during the first 4 hours after anaesthesia was achieved in 58%, 55% and 83% of patients who had received ondansetron, dexamethasone and ondansetron + dexamethasone respectively. The corresponding incidence during the next 20 hours after anaesthesia was 54%, 47% and 85%. No clinically important adverse effects were observed in any of the groups. We conclude that prophylactic therapy with ondansetron +dexamethasone,one is superior in the prevention of postoperative nausea and vomiting after middle ear surgery.     

The efficacy of oral ondansetron and dexamethasone for the prevention of acute chemotherapy‐induced nausea and vomiting associated with moderately emetogenic chemotherapy – a retrospective audit

NG W.L. & DELLA‐FIORENTINA S.A. (2010) European Journal of Cancer Care 19 , 403–407
The efficacy of oral ondansetron and dexamethasone for the prevention of acute chemotherapy‐induced nausea and vomiting associated with moderately emetogenic chemotherapy – a retrospective audit The optimal dose of oral ondansetron for the prevention of acute chemotherapy‐induced nausea and vomiting (CINV) resulting from moderately emetogenic chemotherapy (MEC) is unknown. This retrospective audit was conducted to determine the efficacy of 8 mg oral ondansetron plus 8 mg oral dexamethasone as pre‐chemotherapy anti‐emetic regimen for patients receiving MEC. The efficacy outcomes analysed were the proportion of patients with no acute vomiting, proportion of patients with no acute nausea and the incidence of grade 3 or 4 CINV. A total of 81 patients were identified. The most frequent chemotherapy regimens received in the study population were anthracycline‐ (48%) and carboplatin‐based (28%). No acute vomiting and nausea rates in the study population were 75% and 44% respectively. The incidence of grade 3 CINV was 1%. Patients who received anthracycline‐based regimens had a significantly higher incidence of acute emesis (P= 0.001) and nausea (P < 0.0001) when compared with patients who received non‐anthracycline‐based regimens. In this study, the use of 8 mg oral ondansetron plus 8 mg oral dexamethasone achieved control of acute emesis in 75% of all patients receiving MEC which is comparable to previously reported rates of 70–80%. The benefits of using oral pre‐chemotherapy anti‐emetics include reduction in the costs of drugs and nursing administration time.     

Granisetron is equivalent to ondansetron for prophylaxis of chemotherapy-induced nausea and vomiting: results of a meta-analysis of randomized controlled trials

BACKGROUND: The introduction of serotonin antagonists as antiemetics for prophylaxis of chemotherapy-induced nausea and vomiting represented a major step toward better patient tolerance and adherence to this type of treatment. Several published trials compared different serotonin antagonists without demonstrating clear superiority of any one of them. Because most of these trials compared ondansetron with granisetron, the authors conducted a meta-analysis to determine if the current data available show any therapeutic difference between them. METHODS: MEDLINE and CANCERLIT databases were searched from 1990 to May 1999, and pertinent article references also were surveyed, without restriction to English language. The authors included all randomized controlled trials (RCTs) that had more than 25 patients per arm and compared ondansetron to granisetron for prophylaxis of acute (A) (< 24 hours) and delayed (D) (> 24 hours) nausea (N) and vomiting (V) induced by highly (H) or moderately (M) emetogenic chemotherapy. Only the first chemotherapy cycle was considered for studies that involved a crossover design. RESULTS: Fourteen studies with 6467 evaluable patients among the 21 studies retrieved were selected for this meta-analysis. In none of the eight scenarios studied (AHV, AHN, AMV, AMN, DHV, DHN, DMV, and DMN) could the authors detect any significant differences in the antiemetic efficacy of any of these medications. CONCLUSIONS: The authors conclude that both granisetron and ondansetron have similar antiemetic efficacy for prophylaxis of chemotherapy-induced nausea and vomiting. Because the number of comparative studies that addressed the delayed nausea and vomiting scenarios is low, further RCTs are still needed to confirm these results.     

Ondansetron plus dexamethasone is superior to ondansetron alone in the prevention of emesis in chemotherapy-naive and previously treated patients

BACKGROUND: This prospective, randomized, double-blind study assessed whetherthe addition of dexamethasone to ondansetron leads to improvedcontrol of chemotherapy - induced emesis, both in patients undergoingtheir first course of highly emetogenic chemotherapy and inchemotherapypretreated patients refractory to standard anti-emetics. PATIENTS AND METHODS: Patients were randomized to receive either 20 mg dexamethasoneas an intravenous infusion or placebo plus ondansetron 8 mg15 minutes prior to and 4 and 8 hours after the administrationof chemotherapy. According to the randomisation code patientsreceived from day 2 to day 5 either ondansetron 8 mg p.o. +placebo p.o., three times daily, or ondansetron 8 mg p.o. +dexamethasone 4 mg p.o., three times daily. Patients undergoingmultiple-day treatment received intravenous study treatmenton the days of chemotherapy and thereafter oral treatment asoutlined above. RESULTS: A total of 215 patients were entered into the study. Of these,207 were evaluable (111 previously-untreated and 96 previously-treatedpatients). In the chemotherapynaive patients the combinationof ondansetron plus dexamethasone was significantly superiorto ondansetron plus placebo in protecting the patients completelyfrom emesis (retching and vomiting) (81% versus 64%, p –0.04). The mean number of vomiting episodes was significantlylower in the ondansetron-plus-dexamethasone-treated patientsthan in those receiving ondansetron plus placebo (0.8 versus2.1, p – 0.03). In this group of patients there was significantlysuperior protection from emesis on the second day (pvalue –0.04), and a trend towards a better protection on the thirdand fourth days. On each day the active combination offeredbetter protection from nausea with an approximately 20% differencein favor of ondansetron plus dexamethasone. In the group ofestablished vomiters the combination of ondansetron plus dexamethansonewas superior to ondansetron plus placebo in protecting the patientsfrom acute emesis, with 70% versus 48% of the patients beingcompletely protected (p = 0.03). The mean number of vomitingepisodes was significantly lower in the ondansetron-plusdexamethasone-treated-patientsthan in those receiving ondansetron plus placebo (0.9 versus2.1, p = 0.02). In the ondansetron-plus-dexamethasone arm 55%of the patients had complete protection from nausea, retchingand vomiting compared to 35% in the ondansetron-plus-placebo-treatedgroup (p = 0.05). Overall 22% of the patients (20% in the ondansetronplus-placeboand 25% in the ondansetron-plus-dexamethasone arm) experiencedat least one, usually mild, adverse event. More patients inthe ondansetron-plus-dexamethasone arm complained of epigastricpain or burning (8/101 versus 4/112, p-value = 0.16). The differencein patients reporting constipation (6/101 versus 0/112) washighly significant at a p-value of 0.008. CONCLUSIONS: The combination of dexamethasone plus ondansetron is more effectivein protecting chemotherapynaive patients undergoing their firstcourse of highly emetogenic chemotherapy with cisplatin andchemotherapy-pretreated patients refractory to standard antiemeticsfrom chemotherapy-induced nausea and vomiting compared to ondansetronplus placebo. nausea, vomiting, chemotherapy, ondansetron, dexamethasone, delayed emesis     

枢复宁防止由非顺铂化疗所致呕吐的疗效观察

本文报道用枢复宁十地塞米松与灭吐灵十地塞米松随机对照,控制非顺铂化疗诱发的呕吐。58例病人经随机分组后,28例用枢复宁加地塞米松,30例按本院常用剂量灭吐灵加地塞米松治疗。枢复宁十地塞米松对急性恶心和呕吐的完全控制率均显著高于灭吐灵十地塞米松(分别为87％比72％,P<0.05,94％比67％,P<0.001)。对延缓性呕吐的完全控制。枢复宁十地塞米松也高于灭吐灵十地塞米松,分别为85％—94％比58％—82％(P<0.05)。枢复宁十地塞米松副作用轻,主要有头痛(13％)和便秘(9％),不引起锥体外系反应。因此,枢复宁十地塞米松是一个较为有效的联合止吐方案。     

Delayed emesis induced by moderately emetogenic chemotherapy: Do we need to treat all patients?

Background: The pattern and prognostic factors of delayed nausea andvomiting induced by moderately emetogenic chemotherapy have not yet beenadequately studied.Patients and methods: Data are derived from a large and well definedpopulation of patients studied to evaluate the efficacy and tolerability ofgranisetron, dexamethasone and their combination in the control of acuteemesis over repeated cycles of moderately emetogenic chemotherapy. Patientswere monitored on days 2–5 without receiving any prophylactic treatmentfor delayed emesis.Results: There were 395 evaluable patients at the first, 352 at the secondand 319 at the third cycle of chemotherapy. Overall, 32.7% patientssuffered symptoms of delayed vomiting and/or moderate-severe nausea at thefirst, 32.1% at the second and 35.1% at the third cycle ofchemotherapy. More precisely, the incidence of delayed vomiting was21.3% at the first, 18.5% at the second and 21.0% at thethird cycle of chemotherapy, while the incidence of delayed moderate-severenausea was 25.1%, 25.0% and 26.0%, respectively. Theincidence of delayed vomiting and moderate-severe nausea was very low inpatients who obtained good control of acute vomiting and moderate-severenausea, but it remained substantial in patients who experienced them duringthe first 24 hours after chemotherapy. In fact, at first/second/third cycleof chemotherapy delayed vomiting occurred in12.3%/11.8%/13.1% of patients who did not suffer fromacute vomiting and in 54.1%/48.4%/55.9% of those who hadacute vomiting, respectively. Similar data were obtained for delayedmoderate-severe nausea.Conclusions: Patients without acute vomiting or moderate-severe acutenausea may not need any antiemetic prophylaxis for delayed vomiting or nausea,while those with a history of acute vomiting or moderate-severe acute nauseashould always be treated for delayed emesis. Selection bias and dependenceeffect of delayed emesis on acute emesis can cause misinterpretation of dataderived from clinical trials in patients submitted to multiple cycles ofchemotherapy.