Vomiting In Cancer Patients Research Articles

Clinical and genetic factors associated with nausea and vomiting in cancer patients receiving opioids

Background This study investigates whether demographical, disease-related and genetic factors contribute to inter-individual differences in nausea and vomiting among patients receiving opioids for cancer pain. Methods Cancer patients receiving opioids were included from 17 centres in 11 European countries. Intensities of nausea and vomiting were reported by 1579 patients on four-point categorical scales. In stratified regression models including demographical and disease-related factors as covariates, 96 single nucleotide polymorphisms (SNPs) in 16 candidate genes related to opioid- or nausea/vomiting signalling pathways ( ABCB1, OPRM1, OPRK1, ARRB2, STAT6, COMT, CHRM3, CHRM5, HRH1, DRD2, DRD3, TACR1, HTR3A, HTR3B, HTR3C, CNR1) were analysed for association with nausea and vomiting. Findings Age, body mass index, Karnofsky Performance Status, gender, use of antiemetics, type of opioid, type of cancer and eight SNPs were associated with the inter-individual differences in nausea and vomiting among cancer patients treated with opioids ( p < 0.01). The SNPs were rs1176744, rs3782025 and rs1672717 in HTR3B; rs165722, rs4680 and rs4633 in COMT; rs10802789 and rs685550 in CHRM3. Only the SNP rs1672717 in HTR3B passed the Benjamini–Hochberg criterion for a 10% false discovery rate. Interpretation Clinical characteristics and SNPs within the HTR3B, COMT and CHRM3 genes may be associated with the variability in nausea and vomiting among cancer patients receiving opioids. This knowledge may help to identify patients at particular risk for nausea and vomiting during treatment with opioids for cancer pain.

The Meta-Analysis of the Effect of Acupressure for Nausea and Vomiting in Cancer Patients Receiving Chemotherapy

Purpose: This study was to analyze the characteristics and effect size of intervention studies that used acupressure for the control of chemotherapy-induced nausea and vomiting (CINV). Methods: Nine electronic databases including Korea Education Research and Information, the National Assembly Library, KISS, Korea Med, NDSL, PubMed, EBSCO, Cochrane library, and OVID (to December, 2009) were searched. Thirteen studies of randomized controlled trials (RCTs) or controlled clinical trials (CCTs) were selected. Data were analyzed by SPSS/WIN 18.0. Results: Overall effect size of acupressure was moderate (0.684). Nausea had a moderate effect size (0.770) and nausea and vomiting had a high effect size (0.899). Acupressure using sticker needles had a high effect size (1.368) among finger acupressure, si-acupuncture, and wrist band treatment. Conclusion: This study suggests that acupressure using sticker needles on the spots of nei-guan, chok-samni and hap-kok can reduce the levels of nausea and vomiting in cancer patients receiving chemotherapy. For improving the reliability of the meta-analysis results, further randomized controlled trials with better study methodology are needed.

化学療法による悪心・嘔吐に対するオランザピンの効果

Nausea and vomiting due to chemotherapy not only reduce quality of life but also cause suspension or extension of therapy,or reductions in the dosages of agents used,and influence therapeutic effects.Their control is therefore extremely important.In Olanzapine,one of the multi-acting receptor-targeted antipsychotics,which produce an antimetic effect by acting as an antagonist against multiple receptors related to the mechanism of nausea and vomiting,could be effective in this regard.It is mentioned in the guidelines of the National Comprehensive Cancer Network.In the present study,for patients who developed nausea and vomiting in the initial course of chemotherapy,Olanzapine was administered at 2.5 mg/day from the day prior to the 2 nd course of chemotherapy for 7 days.A comparison of acute and delayed nausea and vomiting symptoms between the initial and 2 nd courses of chemotherapy showed that Olanzapine had no additional effect against acute symptoms but for delayed symptoms,there was a significant improvement in the severity and period of nausea and vomiting.In the future,it will be necessary to accumulate data for many cases in order examine the safety of Olanzapine and dosages for it.

Pharmaceutical interventions facilitate premedication and prevent opioid-induced constipation and emesis in cancer patients

Opioid analgesics possess a number of side effects, among which constipation and nausea/vomiting occur most frequently. Although pretreatment with laxatives and antiemetics for the prophylaxis of opioid-induced constipation and nausea/vomiting, respectively, is recommended, such side effects are still a matter of concern in clinical setting. We first surveyed the prevalence of premedication in 83 cancer patients who took opioid analgesics and the incidence of such side effects. Subsequently, intervention was carried out to promote premedication, and the effectiveness of the intervention was evaluated in 107 patients. Prophylactic treatment with laxatives and antiemetics were conducted in 57% and 52%, respectively. The most frequently prescribed laxatives and antiemetics were magnesium oxide in combination with pantethine, a mild stimulant laxative, and prochlorperazine, respectively. The lack of premedication increased the risk of constipation (odds ratio, 5.25; 95% confidence intervals, 1.93-14.31; p = 0.001) and vomiting (4.67, 1.04-21.04; p = 0.045). Intervention such as provision of drug information to physicians, verification of prescription orders, and instructions to patients increased the rates of prophylactic medications to 93% (p < 0.001) for laxatives and 81% (p < 0.001) for antiemetics. The incidence of side effects was lowered from 36% to 9% (p < 0.001) for constipation, from 28% to 17% for nausea (p = 0.077), and from 16% to 4% for vomiting (p = 0.0085). Intervention to promote prophylactic medication was highly effective in reducing the risk of opioid-induced constipation and nausea/vomiting.

Phase 2 trial results with the novel neurokinin‐1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy‐induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy

This randomized, double-blind, dose-ranging, placebo-controlled, phase 2 trial evaluated the neurokinin-1 receptor antagonist casopitant mesylate in combination with ondansetron/dexamethasone (ond/dex) for the prevention of chemotherapy-induced nausea and vomiting (CINV) related to moderately emetogenic chemotherapy (MEC). Chemotherapy-naive patients who were receiving MEC (N=723) were randomized to receive either oral placebo or casopitant at doses of 50 mg, 100 mg, or 150 mg daily (on Days 1-3) plus ondansetron (on Days 1-3) and dexamethasone (Day 1). Two exploratory arms evaluated single-dose casopitant (150 mg) plus ond/dex and a 3-day casopitant regimen with once-daily ondansetron and dexamethasone. Primary endpoints were rates of complete response (CR) (no vomiting, retching, rescue therapy, or premature discontinuation) and significant nausea (SN) (>or=25 mm on a visual analog scale) over the first 120 hours after Cycle 1 of MEC. Secondary endpoints included acute and delayed CR and SN rates, rates of nausea, vomiting, and safety. All casopitant doses that were tested significantly increased the proportion of patients with CR: The CR rates were 80.8% with casopitant 50 mg, 78.5% with casopitant 100 mg, and 84.2% with casopitant 150 mg compared with 69.4% in the control group (P=.0127); casopitant 150 mg was identified as the minimally effective dose. In exploratory analyses, single-dose casopitant demonstrated a 79.2% CR rate, and once-daily ondansetron plus casopitant produced an 83.5% CR rate. Vomiting rates in the first 5 days after MEC were reduced with casopitant-containing regimens (from 23% to 10%-16%). Rates of SN did not differ among treatment arms (range, 28%-29%). Casopitant appeared to be well tolerated with no notable differences in overall adverse event frequency. Casopitant plus ond/dex was more effective than ond/dex alone for the prevention of CINV.

Naturally Occurring and Related Synthetic Cannabinoids and their Potential Therapeutic Applications

Naturally occurring cannabinoids (phytocannabinoids) are biosynthetically related terpenophenolic compounds uniquely produced by the highly variable plant, Cannabis sativa L. Natural and synthetic cannabinoids have been extensively studied since the discovery that the psychotropic effects of cannabis are mainly due to Delta(9)-THC. However, cannabinoids exert pharmacological actions on other biological systems such as the cardiovascular, immune and endocrine systems. Most of these effects have been attributed to the ability of these compounds to interact with the cannabinoid CB1 and CB2 receptors. The FDA approval of Marinol, a product containing synthetic Delta(9)-THC (dronabinol), in 1985 for the control of nausea and vomiting in cancer patients receiving chemotherapy, and in 1992 as an appetite stimulant for AIDS patients, has further intensified the research interest in these compounds. This article reviews patents (2003-2007) that describe methods for isolation of cannabinoids from cannabis, chemical and chromatographic methods for their purification, synthesis, and potential therapeutic applications of these compounds.

Vitamin B6 Points PC6 Injection During Acupuncture Can Relieve Nausea and Vomiting in Patients With Ovarian Cancer

The impact of chemotherapy-induced nausea and vomiting on the quality of life of ovarian cancer patients is well known. The purpose of this study was to compare the effectiveness of acupuncture plus vitamin B6 PC6 points injection with acupuncture or vitamin B6 alone in controlling emesis of 142 patients undergoing a highly emetogenic chemotherapy regimen between March 1, 2006, and June 30, 2008. The patients were divided into 3 groups randomly and were given different antiemesis treatments accordingly. All patients received the same concurrent antiemetic pharmacotherapy and high-dose chemotherapy. We compared the total number of emesis episodes and the proportion of emesis-free days among the 3 groups during the study period. The acupuncture plus vitamin B6 PC6 points injection group had significantly fewer emesis episodes and a greater proportion of emesis-free days than the acupuncture group or the vitamin B6 alone group. We conclude that acupuncture plus vitamin B6 PC6 point injection is a quite useful method against emesis in cancer patients undergoing chemotherapy.

Randomized Controlled Study Comparing Two Doses of Intravenous Granisetron (1 and 3 mg) for Acute Chemotherapy-induced Nausea and Vomiting in Cancer Patients: A Non-inferiority Trial

The aim of this study was to assess the non-inferiority of 1 mg to 3 mg granisetron (GRN) injection for the treatment of acute chemotherapy-induced nausea and vomiting (CINV) and to evaluate the tolerability of GRN given at 1 mg in Japanese cancer patients. Patients with cancer receiving highly emetogenic chemotherapy were enrolled in this single-blind randomized controlled study. Patients were randomly assigned to receive GRN at a single dose of 1 or 3 mg. The primary endpoint was the rate of complete protection from emetic events (no vomiting, no retching and no need for rescue medication) during the first 24 h following the initiation of chemotherapy. There were 89 patients in the 1 mg group and 90 patients in the 3 mg group. Complete protection was achieved in 70 patients (78.7%) in the 1 mg group and 73 (81.1%) patients in the 3 mg group. The one-sided test did not reveal non-inferiority of either dose of GRN to the other at a 5% significance level. Our data failed to show the non-inferiority of 1 mg of GRN to 3 mg of GRN administered as a single dose. However, the rate of complete protection from nausea and vomiting was similar in the two groups. Given the recommended dosage in the guidelines and the economic need for reduction of medical care expenses in Japan, prophylactic administration of GRN at 1 mg may be an appropriate, alternative treatment for acute CINV in cancer patients.

Preprotachykinin‐A mRNA changes in response to cisplatin‐induced emesis in the least shrew

Cisplatin (CIS) and related drugs cause vomiting in cancer patients. We used the least shrew (Cryptotis parva) emesis model to study this effect, as our previous work has shown that CIS‐treated shrews mimic the biphasic vomiting pattern seen in humans. The acute phase, due presumably to gut and/or medullary serotonin release, occurs within hours. The delayed phase, due presumably to medullary release of substance P (SP), occurs after an emesis‐free period of one (shrews) to several days (humans). We studied the role of SP in CIS‐induced emesis by injecting least shrews with 10 mg/kg CIS (i.p.) and measuring changes in mRNA levels of preprotachykinin‐A (PPTA), the precursor for SP. At different post‐CIS times, tissues from CIS or control shrews were collected and processed for quantitative PCR (QPCR). Whole brain tissue showed a modest increase in PPTA up to 3.5h, a 3 to 14‐fold increase until 33h, then a return to control levels. QPCR of gut tissue showed a rapid rise to 6h, followed by a decrease to below control levels. At 20h, it increased gradually until 33h, then fell below the basal level. Overall, brain PPTA was constantly up‐regulated for 33h, while gut PPTA was upregulated biphasically, coincident with the emetic phases. Thus, SP production in both brain and gut is coordinated with, and may play a role in the modulation of, both phases of CIS‐induced emesis. This study was supported by NIH grant #R01CA115331 to Dr. Darmani.

Randomized Crossover Pharmacokinetic Evaluation of Subcutaneous Versus Intravenous Granisetron in Cancer Patients Treated with Platinum-Based Chemotherapy

5-HT3-receptor antagonists are one of the mainstays of antiemetic treatment, and they are administered either i.v. or orally. Nevertheless, sometimes neither administration route is feasible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to evaluate the bioavailability of s.c. granisetron. Patients receiving platinum-based chemotherapy were randomized to receive 3 mg of granisetron either s.c. or i.v. in a crossover manner during two cycles. Blood and urine samples were collected after each cycle. Pharmacokinetic parameters observed with each administration route were compared by analysis of variance. From May to November 2005, 31 patients were included and 25 were evaluable. Subcutaneous granisetron resulted in a 27% higher area under the concentration-time curve for 0-12 hours (AUC(0-12h)) and higher levels at 12 hours, with similar values for AUC(0-24h). The maximum concentration was lower with the s.c. than with the i.v. route and was observed 30 minutes following s.c. administration. Granisetron administered s.c. achieves complete bioavailability. This is the first study that shows that s.c. granisetron might be a valid alternative to i.v. delivery. Further trials to confirm clinical equivalence are warranted. This new route of administration might be especially relevant for outpatient management of emesis in cancer patients.

Pavlovian conditioning of nausea and vomiting

Cancer patients undergoing cytotoxic drug treatment often experience side-effects, the most distressing being nausea and vomiting. Despite antiemetic drugs, 25–30% of the chemotherapy patients report these side-effects when being re-exposed to the stimuli that usually signal the chemotherapy session and its drug infusion. These symptoms are called anticipatory nausea and anticipatory vomiting. The present paper summarizes the evidence that anticipatory vomiting is acquired by Pavlovian conditioning, and, consequently, may be alleviated by conditioning techniques. To explore the mechanisms that induce and alleviate conditioned nausea and vomiting further, a conditioned nausea model was established in healthy humans using body rotation as the nausea-inducing treatment. The validity of this motion sickness model to examine conditioning mechanisms in the acquisition and alleviation of conditioned nausea was demonstrated. Cortisol and tumor-necrosis factor-α were elevated as endocrine and immunological correlates of nausea. Data in the rotation-induced motion sickness model indicated that gender is an important moderator variable to be considered in further studies. The paper concludes with a review of applications of the demonstrated conditioning principles as interventions to ameliorate distressing anticipatory nausea or anticipatory vomiting in cancer patients undergoing chemotherapy.

Randomized pharmacokinetic evaluation of subcutaneous versus intravenous administration of granisetron in cancer patients treated with platinum-based chemotherapy

8557 Background: 5-HT3 antagonists are one of the mainstays of antiemetic treatment and they can be used either intravenously or orally. Nevertheless sometimes neither intravenous (IV) nor oral administration is possible, such as in patients unable to admit oral intake managed in an outpatient setting. Our objective was to assess if pharmacokinetics of subcutaneous (SC) granisetron were comparable to IV delivery, using Area Under the Curve between 0 and 12 hours (AUC 0–12 h) as our main endpoint. Methods: Patients receiving platinum-based chemotherapy were randomized to receive granisetron 3 mg by either SC or IV administration during the first cycle and by the other route during the second one. Blood samples were drawn at 15, 30, 45, 60, 90 minutes and 2, 3, 4, 6, 8 and 12 hours after granisetron. Drug levels were determined by HPLC with fluorescence detection after liquid-liquid extraction of the samples, with a quantitation limit of 1 ng/ml. Clinical assessment of emesis in both cycles was performed. Results were analyzed using Student’s t-test and Wilcoxon test for paired samples. Assuming a 20% difference in AUC 0–12 h between both routes, 25 patients were required to obtain statistical significance (α=0.05, β=0.10). The protocol was approved by the Ethics Committee and all patients signed informed consent. Results: From May to November 2005, 30 patients were included and 25 of them were evaluable. SC granisetron resulted in a 27% increase in AUC 0–12 h (95% CI: 7–74) and higher levels at 12 hours (see table). Cmax was higher and was reached faster by IV route. Emetic symptoms were equivalent with both alternatives. Conclusion: SC administration of granisetron achieves higher AUC 0–12 h than IV administration, resulting in increased exposition to the drug. This is the first study that shows that SC granisetron is a valid alternative to IV or oral use. This new route of administration might be specially relevant for outpatient management of emesis in cancer patients. [Table: see text] No significant financial relationships to disclose.

Acupuncture-Point Stimulation for Chemotherapy-Induced Nausea and Vomiting [Ezzo J, Vickers A et al. J Clin Oncol 2005; 28: 7188–7199

PurposeAssess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting incancer patients. Materials and MethodsRandomized trials of acupuncture-point stimulation by needles, electricalstimulation, magnets, or acupressure were retrieved. Data were provided by investigators of the original trials and pooled using a fixed-effects model. ResultsEleven trials (N 1,247) were pooled. Overall, acupuncture-point stimulation reduced the proportion of acute vomiting (relativerisks [RR] 0.82; 95% CI, 0.69 to 0.99; P .04), but not the mean number of acute emetic episodes or acute or delayed nausea severity compared with controls. By modality, stimulation with needles reduced the proportion of acute vomiting (RR 0.74; 95% CI, 0.58 to 0.94; P. 01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR 0.76; 95% CI, 0.60 to 0.97; P.02), but manual acupuncture did not; delayed symptoms were not reported. Acupressure reduced mean acute nausea severity (standardized mean difference 0.19; 95% CI, 0.38 to 0.01; P .03) and most severe acute nausea, but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. ConclusionThis review complements data on postoperative nausea and vomiting, suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies with state-of-the-art antiemetics as well as studies for refractory symptoms are needed to determine clinical relevance. Acupressure seems to reduce chemotherapy-induced acute nausea severity, though studies didnot involve a placebo control. Noninvasive electrostimulation seems unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Acupuncture-Point Stimulation for Chemotherapy-Induced Nausea and Vomiting

Assess the effectiveness of acupuncture-point stimulation on acute and delayed chemotherapy-induced nausea and vomiting in cancer patients. Randomized trials of acupuncture-point stimulation by needles, electrical stimulation, magnets, or acupressure were retrieved. Data were provided by investigators of the original trials and pooled using a fixed-effects model. Eleven trials (N = 1,247) were pooled. Overall, acupuncture-point stimulation reduced the proportion of acute vomiting (relative risks [RR] = 0.82; 95% CI, 0.69 to 0.99; P = .04), but not the mean number of acute emetic episodes or acute or delayed nausea severity compared with controls. By modality, stimulation with needles reduced the proportion of acute vomiting (RR = 0.74; 95% CI, 0.58 to 0.94; P = .01), but not acute nausea severity. Electroacupuncture reduced the proportion of acute vomiting (RR = 0.76; 95% CI, 0.60 to 0.97; P = .02), but manual acupuncture did not; delayed symptoms were not reported. Acupressure reduced mean acute nausea severity (standardized mean difference = -0.19; 95% CI, -0.38 to -0.01; P = .03) and most severe acute nausea, but not acute vomiting or delayed symptoms. Noninvasive electrostimulation showed no benefit for any outcome. All trials used concomitant pharmacologic antiemetics, and all, except electroacupuncture trials, used state-of-the-art antiemetics. This review complements data on postoperative nausea and vomiting, suggesting a biologic effect of acupuncture-point stimulation. Electroacupuncture has demonstrated benefit for chemotherapy-induced acute vomiting, but studies with state-of-the-art antiemetics as well as studies for refractory symptoms are needed to determine clinical relevance. Acupressure seems to reduce chemotherapy-induced acute nausea severity, though studies did not involve a placebo control. Noninvasive electrostimulation seems unlikely to have a clinically relevant impact when patients are given state-of-the-art pharmacologic antiemetic therapy.

Delta-9-tetrahydrocannabinol differentially suppresses emesis versus enhanced locomotor activity produced by chemically diverse dopamine D 2/D 3 receptor agonists in the least shrew ( Cryptotis parva)

The principal psychoactive component of marijuana, delta-9-tetrahydrocannabinol (Δ 9-THC), suppresses nausea and vomiting in cancer patients caused by chemotherapeutics such as cisplatin. Cisplatin induces vomiting via a number of emetic stimuli, including dopamine. Currently, there is controversy as to whether Δ 9-THC can prevent emesis produced by dopaminergic agonists such as apomorphine. The present investigation utilizes the least shrew to evaluate the antiemetic potential and the cannabinoid receptor by which Δ 9-THC may prevent emesis produced by four dopamine receptor agonists with differing selectivity for D 2 and D 3 receptors, i.e., a nonselective dopamine receptor agonist (apomorphine), a D 2-preferring receptor agonist (quinpirole), and two D 3-preferring receptor agonists (quinelorane and 7-OH DPAT). In addition, relative to its antiemetic doses, the motor suppressive doses of Δ 9-THC in dopamine D 2/D 3-receptor-agonist-treated shrews were also evaluated. Thus, different groups of shrews were injected with either vehicle (V) or varying doses of Δ 9-THC [0.5, 1, 2.5, 5, or 10 mg/kg, intraperitoneal (i.p.)] 10 min prior to administration of a 2 mg/kg dose of one of the four cited D 2/D 3 agonists. Immediately after the last injection, the frequency of vomiting for each shrew was recorded for the next 30 min. To investigate which cannabinoid receptor is involved in the antiemetic action of Δ 9-THC, various doses of the CB 1 receptor antagonist SR 141716A [0, 5, 10, and 20 mg/kg, subcutaneous (s.c.)] were administered to shrews 10 min prior to an injection of a fully effective antiemetic dose of Δ 9-THC (5 mg/kg, i.p.). Ten minutes later, each treated shrew was administered with a 2 mg/kg dose of apomorphine. The emesis frequency was recorded for the next 30 min. For locomotor studies, different groups of shrews received either vehicle or various doses of Δ 9-THC (0, 5, 10, 20, or 30 mg/kg) 10 min prior to an injection of vehicle or a 2 mg/kg dose of one of the four D 2/D 3 receptor agonists. The triad of motor behaviors (spontaneous locomotor activity, total duration of movement, and rearing frequency) were recorded for the next 30 min by a computerized video tracking system. Δ 9-THC dose-dependently attenuated the frequency of emesis as well as fully protecting shrews from vomiting produced by each one of the four cited dopamine D 2/D 3 receptor agonists with ID 50s ranging from 1 to 4 mg/kg. SR 141716A reversed the antiemetic activity of Δ 9-THC against apomorphine-induced emesis. Δ 9-THC also differentially suppressed the triad of motor activities in dopamine D 2/D 3-receptor-agonist-treated shrews with ID 50s ranging from 7 to 21 mg/kg. The results suggest that Δ 9-THC prevents emesis via cannabinoid CB 1 receptors in a potent and dose-dependent manner in D 2/D 3-receptor-agonist-treated shrews at doses well below those which cause significant motor depression.

Acupressure for nausea and vomiting in cancer patients receiving chemotherapy.

Practitioners working with patients undergoing chemotherapy regularly encourage them to use acupressure in the form of Sea Bands for the relief of treatment-related nausea and vomiting. This mini-review sets out to uncover and examine the evidence base for this recommendation. A mini systematic review was carried out to identify randomized controlled trials comparing the use of acupressure plus usual care with usual care alone. The population was adult patients receiving cancer chemotherapy. The outcome was nausea or vomiting duration or intensity. Searches on Medline, Embase, AMED, the Cochrane Library, Cancerlit and Cinahl identified two randomized controlled trials involving 482 patients with compared acupressure to no intervention control. The results suggest that acupressure may decrease nausea among patients undergoing chemotherapy but further work is required before conclusively advising patients on the efficacy of acupressure in preventing and treating chemotherapy-induced nausea.

Open-label, Randomized Comparison of the Efficacy of Intravenous Dolasetron Mesylate and Ondansetron in the Prevention of Acute and Delayed Cisplatin-induced Emesis in Cancer Patients

The aim of this study is to compare the antiemetic efficacy and tolerability of intravenous dolasetron mesylate and ondansetron in the prevention of acute and delayed emesis. From April 2002 through October 2002, a total of 112 patients receiving cisplatin- based combination chemotherapy were randomized to receive a single i.v. dose of dolasetron 100 mg or ondansetron 8 mg, 30 minutes before the initiation of chemotherapy. In the ondansetron group, two additional doses of ondansetron 8 mg were given at intervals of 2 to 4 hours. To prevent delayed emesis, dolasetron 200 mg p.o. daily or ondansetron 8 mg p.o. bid was administered from the 2(nd) days to a maximum of 5 days. The primary end point was the proportion of patients that experienced no emetic episodes and required no rescue medication (complete response, CR) during the 24 hours (acute period) and during Day 2 to Day 5+/-2 days (delayed period), after chemotherapy. The secondary end points included the incidence and severity of emesis. 105 patients were evaluable for efficacy. CR rates during the acute period were 36.0% for a single dose of dolasetron 100 mg, and 43.6% for three doses of ondansetron 8 mg. CR rates during the delayed period were 8.0% and 10.9%, respectively. There was no significant difference in the efficacy between the two groups. Adverse effects were mostly mild to moderate and not related to study medication. A single i.v. dose of dolasetron 100 mg is as effective as three i.v. doses of ondansetron 8 mg in preventing acute and delayed emesis after cisplatin-based chemotherapy, with a comparable safety profile.

Granisetron: is there a dose-response effect on nausea and vomiting?

Nausea and vomiting are two of the most debilitating side effects of cytotoxic chemotherapy. Prevention of nausea and vomiting is, thus, very important to ensure that cancer patients continue to receive optimal cytotoxic therapy while seeking to maintain their quality of life. Significant advances in antiemetic therapy have been achieved since the introduction of the 5-HT(3) receptor antagonists, and these agents are currently regarded as first-line antiemetic agents. The aim of this article is to examine the hypothesis that there is a dose-response effect of granisetron for preventing chemotherapy-induced nausea and vomiting in cancer patients. A literature review of relevant publications was undertaken to provide a comprehensive review of issues related to the control of chemotherapy-induced emesis with escalating doses of granisetron. There is evidence to suggest that there is a significant trend towards an improved efficacy of granisetron-in both the control of emesis and secondary end-points such as nausea and anorexia-with increasing doses, up to 40 micro g/kg, in adults. At this dose, the likelihood of treatment success may be enhanced for most patients regardless of their individual emetogenic risk. Additionally, incremental doses of granisetron (up to 9 mg) have been shown to be effective and well tolerated in patients with refractory emesis. Those patients experiencing inadequate control of nausea and vomiting following granisetron may also benefit from retreatment with supplementary doses of granisetron, and over subsequent chemotherapy cycles, these patients should receive granisetron 40 micro g/kg to ensure emesis protection.

A Retrospective Chart Review of the Use of Olanzapine for the Prevention of Delayed Emesis in Cancer Patients

Chemotherapy-induced delayed emesis (DE) affects approximately 50–70% of patients receiving moderately and highly emetogenic chemotherapy. DE most commonly occurs within the first 24–48 hours of chemotherapy administration and can persist for 2–5 days. Olanzapine, which has been used anecdotally for chronic nausea in advanced cancer patients, might be a useful treatment for the prevention of delayed emesis in chemotherapy patients. We conducted a chart review to explore this hypothesis and to plan potential studies. Using pharmacy records or an electronic medical record, we identified all patients who had received olanzapine in the oncology clinic (n = 98). We reviewed these records and selected all patients (n = 28) who had received olanzapine for the prevention of delayed emesis for structured review. There were 17 women (60.7%) and 11 men (39.3%). Eleven patients (39.3%) had at least one instance of nausea recorded while undergoing olanzapine treatment and seven (25%) had an episode of vomiting recorded. During 95 total cycles of chemotherapy with olanzapine (mean = 3.4 cycles per patient), there were 21 incidents of nausea (22.1%) and 10 instances of vomiting (10.5%). Side effects were rarely noted. These data suggest that olanzapine was well tolerated and may reduce the incidence of delayed emesis in patients receiving moderate to highly emetogenic chemotherapy. A series of prospective trials are underway.

Factors of Anticipatory Nausea and Vomiting in Cancer Patients

Methods. The conceptual framework was derived from Roy’ s Adaptation Model. The subjects for this study were 66 adult patients with various types of cancers, who were scheduled for a third cycle of chemotherapy or above. Results. 47% of the patients experienced anticipatory nausea and vomiting. Conclusion. The study identified two factors, psychological symptoms (p=.002) and severity of post-chemotherapy nausea and vomiting(p=.004), which are directly related to anticipatory nausea and vomiting. These two factors accounted for 39.5% of the anticipatory nausea and vomiting. Identified environmental cues were awareness of hospital setting, sensory stimuli, and experience of chemotherapy which induced nausea and vomiting. Strategies for relieving anticipatory nausea and vomiting taken by cancer patients were religion, reminiscence, distracting imagery, positive thinking, relaxation and physical exercise.