Antiemetic Therapy In Patients Research Articles

Assessing the impact of aprepitant on response to dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP).

Despite evidence demonstrating the effectiveness of aprepitant for chemotherapy-induced nausea and vomiting (CINV), its use in stem cell transplant settings across Canada is not standard. While pharmacokinetic data exists, the clinical significance of cytochrome P450 3A4 (CYP 3A4) inhibition of cyclophosphamide by aprepitant is unclear. Reduced activation of cyclophosphamide may reduce the effectiveness of dose-intensive cyclophosphamide, etoposide, and cisplatin (DICEP). To compare response rates to DICEP in patients with Hodgkin lymphoma (HL) and diffuse large B-cell lymphoma (DLBCL) in the presence and absence of aprepitant. A retrospective review of patients who received full-dose DICEP for relapsed/refractory HL or DLBCL between June 1995 and September 2018 at the Foothills Medical Centre (FMC) in Calgary, Alberta, Canada was conducted. Descriptive statistics were used to assess response rate, as defined by the 2007 International Working Group response criteria. Of the 218 patients included in this study, 87.6% of patients in the control group and 88.5% of patients in the aprepitant group responded to DICEP (difference 0.025 [95% CI, -0.066 to 0.114], p = 0.827). Univariate analyses for age, sex, type of cancer, stage of cancer, number of prior relapses, and relapse status were not significant. No significant differences were observed for secondary outcomes. Response rates to DICEP in relapsed/refractory HL and DLBCL patients were similar regardless of aprepitant use. Considering these results and the effectiveness of aprepitant in CINV, its addition to standard antiemetic therapy in patients receiving DICEP should be given strong consideration in the transplant setting.

BPI20-016: Comparative Study Between the Clinical Effect of Palonosetron and Granisetron as Antiemetic Therapy for Patients Receiving Highly Emetogenic Chemotherapy Regimens

BPI20-016: Comparative Study Between the Clinical Effect of Palonosetron and Granisetron as Antiemetic Therapy for Patients Receiving Highly Emetogenic Chemotherapy Regimens

1764P - A phase III trial evaluating olanzapine 5 mg for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin: J-FORCE study

BackgroundOlanzapine (OLZ) 10mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by cisplatin. Guidelines suggest that OLZ at a dose of 5mg should be taken into consideration in patients at risk of sedation. OLZ 5mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5mg in addition to standard antiemetic therapy for the prevention of CINV. MethodsPatients receiving cisplatin (≥ 50mg/m2) were randomly assigned to either OLZ 5mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120h). As the secondary endpoints, frequency of sleepiness during daytime and appetite loss were assessed by patient reported outcome. ResultsA total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was significantly increased with OLZ than with placebo (79% vs. 66%, P<0.001). CR in the acute (0–24h) and overall (0–120h) phase was also significantly increased with OLZ (95% vs. 89%, P=0.002, and 78% vs. 64%, P<0.001, respectively). Although the proportion of sleepiness during daytime was higher in the OLZ group than the placebo group on day 1 (75% vs. 68%, P=0.002), there was no difference found on days 2–5 between the two groups. The proportion of patients who reported appetite loss was significantly lower in the OLZ group than the placebo group on days 2–5 (P<0.001). ConclusionsOLZ 5mg can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Sleepiness during daytime due to OLZ 5mg seems to be tolerable and addition of OLZ 5mg to the standard antiemetic therapy may reduce appetite loss. Legal entity responsible for the studyMasakazu Abe. FundingJapan Agency for Medical Research and Development. DisclosureS. Iwasa: Honoraria (self): Taiho pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self): Ono Pharmaceutical; Research grant / Funding (institution): Daiichi Sankyo; Research grant / Funding (institution): Bristol-Myers Squib; Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Merck Serono; Research grant / Funding (institution): Otsuka; Research grant / Funding (institution): Bayer. N. Yamamoto: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self), Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Lilly Japan; Research grant / Funding (institution): Taiho Pharmaceutical; Advisory / Consultancy, Research grant / Funding (institution): Eisai; Research grant / Funding (institution): Astellas Pharma; Research grant / Funding (institution): Novartis; Research grant / Funding (institution): Daiichi Sankyo; Advisory / Consultancy, Research grant / Funding (institution): Boehringer Ingelheim; Advisory / Consultancy, Research grant / Funding (institution): Takeda; Research grant / Funding (institution): Kyowa Hakko Kirin; Research grant / Funding (institution): Bayer; Research grant / Funding (institution): Janssen; Research grant / Funding (institution): IQVIA; Research grant / Funding (institution): MSD; Research grant / Funding (institution): Abbvie; Research grant / Funding (institution): Merck Serono. Y. Ohe: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Chugai Pharma; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Lilly Japan; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Shareholder / Stockholder / Stock options, An Immediate Family Member : Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Novartis; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Kyorin; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: Celltrion; Honoraria (self), Advisory / Consultancy: Amgen; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb Japan; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bayer; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): Taiho pharmaceutical; Honoraria (self): Kyowa Hakko Kirin; Research grant / Funding (institution): Sumitomo Dainippon Pharma; Research grant / Funding (institution): Ignyta. All other authors have declared no conflicts of interest.

A randomized, double-blind, placebo-controlled phase III trial evaluating olanzapine 5 mg combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based chemotherapy: J-FORCE Study.

11503 Background: Olanzapine (OLZ) 10 mg added to standard antiemetic therapy including aprepitant (APR), palonosetron (PALO), and dexamethasone (DEX) has been recommended for the prevention of chemotherapy-induced nausea and vomiting (CINV) caused by highly emetogenic chemotherapy (HEC). Guidelines suggest that a dose of 5 mg should be taken into consideration in patients at risk of sedation. OLZ 5 mg showed an equivalent activity and favorable toxicity to somnolence in several phase II studies. We conducted a randomized, double-blind, placebo-controlled phase III trial to evaluate OLZ 5 mg in addition to standard antiemetic therapy for the prevention of CINV in patients receiving cisplatin-based chemotherapy. Methods: Patients receiving cisplatin (≥ 50 mg/m2) were randomly assigned to either OLZ 5 mg or placebo on days 1–4, combined with APR, PALO and DEX. The primary endpoint was complete response (CR), defined as no vomiting and no rescue medications in the delayed phase (24–120 h). A total of 690 patients were required to detect a 10% increase in CR from 65% in the placebo to 75% in the OLZ, with a one-sided alpha of 2.5% and a power of 80%. Results: A total of 710 patients were enrolled (OLZ 356 and placebo 354). CR in the delayed phase was 79.1% (95% CI: 74.9–83.3) in the OLZ 5 mg and 65.8% (95% CI: 60.9–70.8) in the placebo ( p &lt; 0.001). Other efficacy results are summarized in Table. The most common treatment-related adverse events was somnolence (43.1% for OLZ vs. 33.0% for placebo). Conclusions: OLZ 5 mg combined with APR, PALO and DEX can be considered a new standard antiemetic therapy in patients receiving cisplatin-based chemotherapy. Clinical trial information: UMIN000024676. [Table: see text]

Comparative Cost-utility Analysis Between Aprepitant- and Fosaprepitant-containing Regimens To Prevent Chemotherapy-induced Nausea and Vomiting in Patients Receiving Highly Emetogenic Chemotherapy in Japan

PurposeClinical trials have shown that the addition of aprepitant (APR) or a phosphorylated prodrug of aprepitant, fosaprepitant (FosAPR) as prophylactic antiemetic therapy consisting of a 5-hydrotryptamine-3 receptor antagonist and dexamethasone is effective in patients receiving highly emetogenic chemotherapy. These combination therapies have been commonly used in Japan. In the present study, we performed a cost-utility analysis of APR and FosAPR in the context of the Japanese medical insurance system, and economic efficiency was compared. MethodsData from randomized controlled trials that examined the efficacy of APR and FosAPR in the Japanese population were used. A decision tree was constructed to estimate the effectiveness of chemotherapy for 5 days from the day of the treatment and the cost associated with outpatient chemotherapy from the perspective of a payer. Health outcome was expressed in quality-adjusted life-years (QALYs), and costs were estimated based on medical fees and drug prices from 2018. An incremental cost-effectiveness ratio (ICER) was calculated for each regimen containing either APR or FosAPR. The robustness of the model was assessed using 1-way and probabilistic sensitivity analysis. FindingsThe base-case analysis estimated that the addition of APR or FosAPR would have incremental effects of 0.00166 and 0.00143 QALY and incremental costs of 8305 and 11,348 JPY (74 and 101 USD [1 USD = 112.17 JPY]), resulting in ICERs of 4,992,172 and 7,955,560 JPY/QALY (44,505 and 70,924 USD/QALY), respectively. Sensitivity analysis revealed that the probability of a complete response for delayed chemotherapy-induced nausea and vomiting had the most influence on the ICERs. Reductions in the drug costs of APR and FosAPR also had an effect on the ICERs. According to the probabilistic sensitivity analysis, APR and FosAPR were dominant in terms of cost-effectiveness in 48.7% and 8.55% of cases, respectively. ImplicationsThe ICER of outpatient prophylactic antiemetic therapy in patients receiving highly emetogenic chemotherapy was calculated in the context of the Japanese medical insurance system. Assuming the willingness-to-pay of 5,000,000 JPY/QALY based on the calculated ICER, our findings suggest that although the addition of APR is cost-effective, FosAPR is not cost-effective.

O1-11-5 - Serum iron levels increased by cancer chemotherapy correlate the chemotherapy-induced nausea and vomiting

The pathogenesis of chemotherapy-induced nausea and vomiting (CINV) is not fully elucidated. We hypothesized that serum iron levels may be associated with CINV because symptoms of iron poisoning resemble the adverse effects of chemotherapy. Patients with lung cancer undergoing chemotherapy were included in this retrospective study where serum iron level, unsaturated iron-binding capacity (UIBC), total iron-binding capacity, and ferritin were available prior to and on days 2 and 8 of chemotherapy. Fifty-two patients were analyzed. Iron levels on day 2 were markedly increased in patients receiving highly emetogenic chemotherapy (HEC, 231.0 ± 45.0 µg/dl) and moderately emetogenic chemotherapy (MEC, 226.6 ± 44.2 µg/dl), and mildly increased in patients receiving low emetogenic chemotherapy (LEC, 104 ± 51.4 µg/dl). Significant differences in iron levels on day 2 were observed between the HEC and LEC (P = 0.002) and MEC and LEC (P = 0.0007) groups. UIBC levels decreased on day 2 (18.0 ± 17.5 µg/dl in HEC, 20.4 ± 46.8 µg/dl in MEC, and 123.9 ± 65.9 µg/dl in LEC). There were significant differences in UIBC on days 2 between the HEC and LEC (P = 0.0005) and MEC and LEC (P = 0.0015) groups. No significant changes in these parameters were observed in a minimal risk group. Iron levels increased according to the emetogenic risk. Accompanied by a markedly increased iron level, non-transferrin bound iron, a highly cytotoxic form of iron, may be present in the serum. Iron removal with an iron-chelating agent may represent a novel antiemetic therapy in patients undergoing chemotherapy.

Serum iron levels increased by cancer chemotherapy correlate the chemotherapy-induced nausea and vomiting

BackgroundThe pathogenesis of chemotherapy-induced nausea and vomiting (CINV) is not fully elucidated. We hypothesized that serum iron levels may be associated with CINV because symptoms of iron poisoning resemble the adverse effects of chemotherapy.MethodsPatients with lung cancer undergoing chemotherapy were included in this retrospective study where serum iron level, unsaturated iron-binding capacity (UIBC), total iron-binding capacity, and ferritin were available prior to and on days 2 and 8 of chemotherapy.ResultsFifty-two patients were analyzed. Iron levels on day 2 were markedly increased in patients receiving highly emetogenic chemotherapy (HEC, 231.0 ± 45.0 µg/dl) and moderately emetogenic chemotherapy (MEC, 226.6 ± 44.2 µg/dl), and mildly increased in patients receiving low emetogenic chemotherapy (LEC, 104 ± 51.4 µg/dl). Significant differences in iron levels on day 2 were observed between the HEC and LEC (P = 0.002) and MEC and LEC (P = 0.0007) groups. UIBC levels decreased on day 2 (18.0 ± 17.5 µg/dl in HEC, 20.4 ± 46.8 µg/dl in MEC, and 123.9 ± 65.9 µg/dl in LEC). There were significant differences in UIBC on days 2 between the HEC and LEC (P = 0.0005) and MEC and LEC (P = 0.0015) groups. No significant changes in these parameters were observed in a minimal risk group.ConclusionsIron levels increased according to the emetogenic risk. Accompanied by a markedly increased iron level, non-transferrin bound iron, a highly cytotoxic form of iron, may be present in the serum. Iron removal with an iron-chelating agent may represent a novel antiemetic therapy in patients undergoing chemotherapy.

A randomized open-label study of guideline-driven antiemetic therapy versus single agent antiemetic therapy in patients with advanced cancer and nausea not related to anticancer treatment

BackgroundNausea/vomiting (N/V) not related to anti-cancer treatment is common in patients with advanced cancer. The standard approach to management is to define a dominant cause, and treat with an antiemetic selected through pathophysiologic knowledge of emetic pathways. High rates of N/V control have been reported using both etiology-based guideline-driven antiemetic regimens and an empiric approach using single agents in uncontrolled studies. These different approaches had never been formally compared.MethodsThis randomized, prospective, open label, dose-escalating study used readily available antiemetics in accordance with etiology-based guidelines or single agent therapy with haloperidol. Participants had a baseline average nausea score of ≥3/10. Response was defined as a ≥ 2/10 point reduction on a numerical rating scale of average nausea score with a final score < 3/10 at 72 h.ResultsNausea scores and distress from nausea improved over time in the majority of the 185 patients randomized. For those who completed each treatment day, a greater response rate was seen in the guideline arm than the single agent arm at 24 h (49% vs 32%; p = 0.02), but not at 48 or 72 h. Response rates at 72 h in the intention to treat analysis were 49 and 53% respectively, with no significant difference between arms (0·04; 95% CI: -0·11, 0·19; p = 0·59). Over 80% of all participants reported an improved global impression of change. There were few adverse events worse than baseline in either arm.ConclusionAn etiology-based, guideline-directed approach to antiemetic therapy may offer more rapid benefit, but is no better than single agent treatment with haloperidol at 72 h.Clinical trial registrationAustralian New Zealand Clinical Trials Registry: ANZCTRN12610000481077.

Efficacy of antiemetic therapy in patients undergoing laparoscopic cholecystectomy

IntroductionA high incidence of postoperative nausea and vomiting has been observed in patients undergoing laparoscopic cholecystectomy (20–40%). This causes an increase in patient discomfort, a delay in recovery, and an increase in hospital stay. ObjectiveCompare the efficacy of ondansetron plus metoclopramide and ondansetron alone in the control of postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy. Material and methodsA comparative, prospective, experimental, longitudinal double blind study was performed with 30 patients programmed for laparoscopic cholecystectomy. The Apfel score was applied postoperatively. Patients were divided into two groups with 15 participants. Metoclopramide 10mg and ondansetron 4mg were administered in the first Group (A), and ondansetron 4mg in the second Group (B), after induction of anesthesia. Nausea and vomiting were evaluated for 24h postoperatively using a Likert scale. ResultsOf the patients who presented nausea, the condition was mild. The patient who presented vomiting, vomited only once. Neither group required rescue drugs. Regarding the Apfel score, there was no correlation between the percentage of stratified risk and the patients who presented postoperative nausea and vomiting. ConclusionsNo statistically significant difference was observed between ondansetron plus metoclopramide and ondansetron alone in patients subjected to laparoscopic cholecystectomy.

Cancer-related fatigue: can it be due to adrenal suppression secondary to high-dose steroids used as antiemetic?

To the editor: The use of dexamethasone for cancer-related fatigue (CRF) in patients with advanced cancer is a controversial issue. Beneficial effects of dexamethasone may be counterbalanced by its serious side effects. The exact mechanism of the action of steroids on cancer-related fatigue is unknown. Recently, Yennurajalingam et al. hypothesized that dexamethasone exerts its effects on CRF mainly by interfering with the peripheral effects of proinflammatory cytokines [1]. We believe that this may not be the case for some of patients with CRF. The exact pathogenesis of CRF is unknown. A role of systemic inflammation or imbalance between hypothalamicpituitary-adrenal (HPA) axis and systemic cytokines has been proposed [2, 3]. Advanced stage cancer represents a state of chronic stress. Low levels of endogenous cortisol, which may be associated with symptoms in advanced cancer, had been demonstrated by Lundstrom et al. [4]. Major symptoms of adrenal insufficiency (i.e., fatigue, nausea, loss of appetite) may be misinterpreted as CRF. Indeed, some patients treated for CRF may have unrecognized adrenal insufficiency. High dose of dexamethasone (8–16 mg/day) is commonly used as antiemetic therapy in highly and moderately emetic regimens. Updated ASCO guidelines on antiemetics recommend a 4-day course of dexamethasone (12 mg on day 1 and 8 mg on days 2–4) for highly emetogenic chemotherapy and 1–3-day 8 mg course for moderately emetogenic chemotherapy [5]. Highdose steroids may suppress the hypothalamic pituitary and adrenal axis, even with short-term use [6]. Han et al. published their article on adrenal suppression related to the use of dexamethasone as an antiemetic therapy in patients with cancer in July 2012 [7]. Patients receiving dexamethasone as an antiemetic for at least 3 days per cycle and for more than 3 months were included in this study. Adrenal suppression was demonstrated biochemically in 45 of the 103 patients (43.7 %). Adrenal suppression was more common in patients receiving megestrol acetate concomitantly. Daily replacement therapy with 7.5–10 mg of prednisolone for 1–2 weeks in patients with suppressed HPA axis resulted in the improvement of symptoms associated with adrenal insufficiency. This dose of prednisolone is approximately equivalent to 1 mg of dexamethasone [8]. This is about one eighth of the dose recommended in the study of Yennurajalingam et al. We believe that this lower dose may allow the use of steroid for longer periods and spare some of the patients with CRF from serious side effects of higher doses of steroids. Metabolic (i.e., hyperglycemia, hypokalemia) and muscular side effects (i.e., proximal muscle weakness) of long-term use of steroids may be confused with CRF or even increase the severity of CRF. Lower dexamethasone dose will probably cause less metabolic and muscular side effects. For those patients with continuing symptoms of CRF, steroid dose may be gradually increased. In the current study, no follow up for the quality of life was made after cessation of dexamethasone [1]. As CRF is a chronic problem, symptoms may become worse after cessation of high-dose dexamethasone. Lesser dose of dexamethasone may be used more safely for longer periods of time for some patients with this chronic problem. There are still unanswered questions about CRF: What should be done for patients without biochemical evidence of HPA axis suppression? Should we search for biochemical evidence of inflammation (i.e., C-reactive protein) in this group of patients? Should we start with higher doses of dexamethasone when we have laboratory evidence of both systemic inflammation and HPA axis suppression? Should adrenal insufficiency be in the routine checklist of evaluation O. O. Eren (*) :B. Oyan Medical Oncology Section, Department of Internal Medicine, Yeditepe University Hospital, Devlet yolu, Ankara Caddesi, 102-104 Istanbul, Turkey e-mail: droneren@hotmail.com

Efficacy of Aprepitant in Patients with Advanced or Recurrent Lung Cancer Receiving Moderately Emetogenic Chemotherapy

To evaluate the efficacy of a combination of aprepitant and conventional antiemetic therapy in patients with advanced or recurrent lung cancer receiving moderately emetogenic chemotherapy (MEC). Patients with advanced or recurrent lung cancer who were treated with MEC regimens at the Department of Respiratory Medicine, Fukuoka University Hospital, were included and classified into the following groups: control group (treatment: 5-HT3 receptor antagonists + dexamethasone) and aprepitant group (treatment: 5-HT3 receptor antagonists + dexamethasone + aprepitant). The presence or absence of chemotherapy-induced nausea and vomiting (CINV) was evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE) v4.0; patients with grade 1 or above were considered positive for CINV. Food intake per day, completion of planned chemotherapy, and progression-free survival (PFS) achieved by chemotherapy were investigated. The complete suppression rate of nausea in the aprepitant group was significantly higher than that in the control group (p = 0.0043). Throughout the study, the food intake in the aprepitant group was greater than that in the control group, with the rate being significantly higher, in particular, on day 5 (p = 0.003). The completion rate of planned chemotherapy was also higher in the aprepitant group (p = 0.042). PFS did not differ significantly, but tended to be improved in the aprepitant group. The aprepitant group showed significantly higher complete suppression of nausea, food intake on day 5, and completion of planned chemotherapy than the control group.

Active combination with aprepitant, palonosetron, and dexamethasone for preventing emesis of anthracycline-containing regimens in patients with breast cancer.

e19512 Background: Anthracycline and cyclophoshamaide containing regimens for breast cancer are classified as highly emetogenic chemotherapy. Aprepitant (A), palonosetron (P), granisetron (G) or dexamethasone(D) are recommended as antiemetic drugs. However, it is uncertain which combination would be best effective. We have retrospectively examined the efficacy of these antiemetic drugs. Methods: We reviewed the medical records of 501 patients with breast cancer treated with anthracycline and cyclophoshamaide containing regimens between August, 2009 and September, 2010. The combination of GD were G: 3 mg on day1 (i.v.), 2 mg on days 2-6 (p.o.) and D: 16.5 mg on day1 (i.v.), 8mg on days 2-4 (p.o.). The AGD were A: 125 mg on day1 (i.v.), 80 mg on days 2-3 (p.o.), G: 3 mg on day1 (i.v.), 2 mg on days 2-6 (p.o.), and D: 13.2 mg on day1 (i.v.), 4 mg on days 2-4 (p.o.). The APD were A: 125 mg on day1 (i.v.), 80 mg on days 2-3 (p.o.), P: 0.75 mg on day1 ( i.v.), and D: 13.2 mg on day1 (i.v.), 4 mg on days 2-4 (p.o.). Results: The number of patients who were treated with GD, AGD, and APD were 170, 159, and 172, respectively. Complete response (CR) rate in acute phase (0-24h) or delayed phase (24-120h) and complete control (CC) rate in acute or delayed phase in each regimens were summarized in the table. AGD or APD was significantly superior to GD in CR rate of acute or delayed phase (P&lt;0.01). Of note, CC rate of APD in acute phase was significantly superior to AGD (P&lt;0.01). AGD or APD was significantly superior to GD in CC rate in delayed phase. Conclusions: The combination with APD was the most effective antiemetic therapy in patients who were treated with anthracycline and cyclophosphamide containing regimens. [Table: see text]

P43 Efficacy of antiemetics in patients receiving XELOX – A single-centre, prospective study

Background: XELOX (combination therapy of capecitabine and oxaliplatin) is known to cause nausea and vomiting, despite adequate administration of antiemetics. Furthermore, specific risk factors that may increase the risk of nausea and vomiting are unknown. Methods: This was a single-centre, prospective, cohort study. Patients were recruited on the day of chemotherapy, and were followed up after 5 days to assess nausea, vomiting, and use of antiemetics. Patients were assessed for nausea and vomiting control, as well as complete response, complete protection, and complete control of antiemetics. Use of delayed and breakthrough antiemetics were assessed, and multivariable logistic regression was done to evaluate risk factors that predisposed patients to nausea and vomiting despite use of antiemetics. Findings: 156 patients were included in this analysis. The median age was 60 years (IQR 55–65) with 88 (56.4%) men and 68 (43.6%) women. The proportion of patients achieving complete response, complete protection, and complete control within 24 hours after chemotherapy was 87.8%, 80.8%, and 62.8%, respectively. These proportions continued to decline throughout the follow-up period to 76.9%, 64.7%, and 48.7%, respectively, at the end of the 5 days. Patients who had fewer than three risk factors (odds ratio [OR] 3.13, p=0.006), who received oxaliplatin less than 100mg/m2 (OR 3.23, p=0.009), and who received capecitabine less than 1500mg/m2 (OR 5.00, p=0.04) were more likely to achieve complete response to antiemetics. Interpretation: This study showed that an unacceptably high proportion of patients receiving XELOX were unable to attain adequate control of nausea. Future research should focus on the optimisation of antiemetic therapy for patients receiving XELOX. Funding: National University of Singapore, Faculty of Science start-up grant. The authors declared no conflicts of interest.

Aprepitant vs. Multimodal Prophylaxis in the Prevention of Nausea and Vomiting following Extended-Release Epidural Morphine

Extended-release epidural morphine (EREM) is an effective option for postoperative analgesia following major orthopedic surgery; however, postoperative nausea/vomiting (PONV) is a recognized limitation. The incidence of PONV following prophylactic aprepitant, a neurokinin-1 antagonist, was compared with prophylactic multimodal antiemetic therapy in patients receiving EREM for postoperative analgesia following unilateral primary total knee arthroplasty (TKA). Prospectively collected quality assurance data were examined with Institutional Review Board approval. A sequential, open-label, active matched case-control study compared PONV following EREM in patients receiving ondansetron and dexamethasone, and either metoclopramide, diphenhydramine, or prochlorperazine every 6 hours for the 48-hour study period, to patients receiving aprepitant 40 mg given as a single oral dose in the preoperative holding area. Cases were matched for procedure (TKA), age, epidural morphine dose, and known major risk factors for PONV (sex, smoking, previous PONV/motion sickness). Twelve consecutive patients (3 male; 9 female) receiving aprepitant prior to EREM were matched to 12 patients of the same sex of similar age (range 51 to 84 years.) and EREM dose (range 5 to 12.5 mg) receiving the multimodal regime. The incidence of PONV was significantly less for the aprepitant group where 3 of 12 (25%) had PONV compared with 9 of 12 (75%) in the multimodal group (P = 0.039, Fisher's Exact Test; odds ratio = 0.11; 95% CI: 0.018 to 0.706, P = 0.03). While aprepitant significantly reduced the incidence of PONV compared with a multimodal antiemetic regime, used alone it did not eliminate PONV.

Optimizing antiemetic therapy in multiple-day and multiple cycles of chemotherapy

Only a few studies have investigated the effect of antiemetic therapy in patients treated with multiple-day or multiple cycles of chemotherapy. The present review will assess the available data, highlight the current recommendations and draw attention towards the remaining problems in this field of antiemetic treatment. Evidence-based guidelines recommend a combination of a 5-HT3-receptor antagonist and dexamethasone in the prophylaxis of nausea and vomiting in multiple-day cisplatin-based chemotherapy. In patients treated with multiple cycles of chemotherapy the addition of a NK1-receptor antagonist aprepitant to standard antiemetic therapy has increased the antiemetic effect, and multiple cycle extension studies have demonstrated that this increment in effect is sustained during multiple cycles of chemotherapy. A recent study indicated that the dopamine D2-receptor antagonist metopimazine has some additive effect on delayed symptoms induced by multiple-day chemotherapy. The development of the NK1-receptor antagonist aprepitant has significantly improved the antiemetic control in patients treated with multiple cycles of chemotherapy. Far too many patients still experience considerable emetic side effects. The effect of aprepitant in multiple-day chemotherapy has yet to be defined. The effect of new antiemetic agents such as palonosetron and olanzapine also needs to be investigated in randomized trials.

A comparative study of haloperidol or dexamethasone plus ondansetron as prophylactic antiemetic therapy in patients at high risk of postoperative nausea and vomiting

A comparative study of haloperidol or dexamethasone plus ondansetron as prophylactic antiemetic therapy in patients at high risk of postoperative nausea and vomiting

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

To compare the antiemetic efficacy and tolerability of tropisetron plus metopimazine with tropisetron plus placebo during 4 cycles of multiple-day, cisplatin-based chemotherapy. 82 chemotherapy-naive patients with germ cell cancer scheduled to 4 cycles of multiple-day cisplatin-based chemotherapy (20 or 40 mg/m(2)/day for 5 days) given every 3 weeks were included. A double-blind parallel trial design was used and patients randomized to tropisetron plus metopimazine or tropisetron plus placebo. Tropisetron was administered as a single 5 mg intravenous dose on days 1-5 and a single 5 mg oral dose on day 6, and metopimazine as 30 mg orally t.i.d. on day 1, and q.i.d on days 2-6. Patients were evaluable for efficacy during a total of 195 cycles. Small, but certain advantages were obtained with the combination. In cycle 1, complete protection from emetic episodes on day 1, days 1-5, days 6-9 and days 1-9 was achieved in 85.7%, 42.9%, 86.2% and 40.5% with tropisetron plus metopimazine and in 90.0%, 22.5%, 64.3% and 17.5% with tropisetron plus placebo, respectively. This difference achieved statistical significance in the overall period, days 1-9 (P = 0.029). During the entire period (days 1-9), significantly less nausea was seen in patients receiving tropisetron plus metopimazine (P = 0.027), whereas other nausea parameters did not reach statistical significance. The cumulative emetic protection rate after 4 cycles was 0.51 with tropisetron plus metopimazine and 0.25 with tropisetron plus placebo (P = 0.037). Side effects were generally few and mild with both treatments and no significant differences were seen. Tropisetron plus metopimazine is superior to tropisetron during 4 cycles of multiple-day cisplatin-based chemotherapy, but both treatments are ineffective in a number of patients. The effect of the combination seems comparable to that of ondansetron plus dexamethasone. Newer drugs such as the neurokinin(1) receptor antagonist, aprepitant, should be investigated to optimize antiemetic therapy in patients receiving multiple-day chemotherapy.

A comparative study of dexamethasone plus midazolam, ondansetron, or saline as prophylactic antiemetic therapy in patients at high risk of postoperative nausea and vomiting

A comparative study of dexamethasone plus midazolam, ondansetron, or saline as prophylactic antiemetic therapy in patients at high risk of postoperative nausea and vomiting

Prophylaxis versus treatment: Is there a better way to manage radiotherapy-induced nausea and vomiting?

Nausea and vomiting are two of the most distressing side effects of radiotherapy and cytotoxic drugs, which currently are often combined to treat moderately advanced and advanced solid tumors. Inadequate control of these symptoms may result in significant patient suffering and decrease in the patient's quality of life, which has been shown to decrease patients' compliance to treatment, with potential impact on disease outcome. It is, therefore, important that radiation oncologists recognize the need for adequate prophylactic treatment of radiation-induced nausea and vomiting (RINV) to avoid the detrimental effects on patients' quality of life, and optimize chances for cure. The 5-hydroxytryptamine type 3 (5-HT(3))-receptor antagonists have been proved to provide effective antiemetic therapy in patients undergoing highly emetogenic radiotherapy. Nevertheless, several large surveys have shown that optimal treatments are not always used. Hence, a risk exists that waiting for RINV symptoms rather than prescribing prophylactic antiemetic treatment may lead to increased patient suffering, poorer disease control, and less cost-effective therapy options. Prophylactic management with an effective 5-HT(3)-receptor antagonist should offer a better treatment option for patients at high to moderate risk of RINV. Adequate control of RINV should contribute to patient compliance to treatment, improved therapy outcomes, and decreased burdens on nursing and health care resources.

Pharmacokinetics, Tolerability and Efficacy of Bolus-Dose vs Continuous-Infusion Granisetron in the Prevention of Vomiting in Patients Undergoing Haematopoietic Stem-Cell Transplantation

Objective: We compared bolus-infusion with continuous-infusion administration of granisetron antiemetic therapy in patients undergoing haematopoietic stem-cell transplantation.