Vomiting In Cancer Patients Research Articles

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.

The Development of a Protocol for the Use of 5–HT3 Antagonists in Chemotherapy-Induced Nausea and Vomiting

The purpose of this study was to evaluate the effectiveness of three 5–HT3 antagonists in routine clinical practice. The ultimate aim was to develop an antiemetic protocol, selecting a single 5–HT3 antagonist. Each of the drugs was studied for a 4–month period and data was collected from patients on nausea, vomiting (both acute and delayed) and side-effects by means of a diary card. A total of 274 patients were enrolled into the study.Success rates for acute emesis seen over the study period were in excess of 90%. There were no statistically significant differences between any of the three drugs investigated with respect to both acute and delayed nausea and vomiting. Similarly, there was no difference between the three groups for the incidence of constipation, diarrhoea and headache.Granisetron demonstrated a lesser deviation from the protocol in respect of the number of intravenous doses given to patients.The study allowed an effective 5–HT3 antagonist protocol to be developed for use in the management of nausea and vomiting in cancer patients.

Potential role of the NK1 receptor antagonists in chemotherapy-induced nausea and vomiting.

Better tolerated and more effective means of controlling chemotherapy-induced nausea and vomiting have been introduced over the past decade. Despite the progress made, incompletely controlled emesis is a persistent problem for significant numbers of patients receiving chemotherapy. Efforts to improve antiemetic control further are ongoing. The most interesting new class of antiemetics under development focuses on antagonism of the neurotransmitter substance P. Substance P exerts its effects by binding to the tachykinin neurokinin NK1 receptor. A number of selective antagonists of the NK1 receptor have been synthesized and, when used in preclinical models, have demonstrated an ability to antagonize the emetic effects of a number of stimuli, including chemotherapy agents such as cisplatin. Over the past 3 years, results of the initial studies evaluating this class of agents for cisplatin-induced emesis in cancer patients have begun to appear. These agents have been well tolerated. As single agents, they appear to be no more effective than 5-HT3 receptor antagonists in preventing acute cisplatin-induced emesis. Their real value may be found in combination with existing agents and in the treatment of delayed emesis. The results of ongoing clinical trials will hopefully define the utility and appropriate place for this new class of agents in the management of chemotherapy-induced nausea and vomiting.

A stochastic model to analyse risk factors for emesis in multi-cycle chemotherapies

Abstract We propose a stochastic model to analyse risk factors for emesis in multi-cycle chemotherapies, which allows to describe the effect of a potential risk factor by a single parameter. This model is a hybrid between a random intercept model and a transition model and it is motivated by some medical background knowledge with respect to frequency and course of emesis in cancer patients. We consider maximum likelihood estimation of the parameters of the model and additionally efficient estimation of the marginal risk in the first cycle. Finite sample properties are investigated in a simulation study. The proposed model suffers from a slight overparametrization, such that ML estimates show some poor statistical properties, but estimates of the marginal risk behave quite well. An investigation of alternative, simpler regression models reveals, that in this setting these models allow to define a time-constant regression coefficient only in a somewhat arbitrary manner. Hence we conclude, that the proposed model is valuable in spite of the difficulties with respect to parameter estimation.

Δ9-Tetrahydrocannabinol and Synthetic Cannabinoids Prevent Emesis Produced by the Cannabinoid CB1 Receptor Antagonist/Inverse Agonist SR 141716A

There is substantial clinical evidence that Δ9-tetrahydrocannabinol (Δ9-THC) and its synthetic analogs (nabilone and levonantradol) can prevent emesis in cancer patients receiving chemotherapy. Limited available animal studies also support the antiemetic potential of these cannabinoids. The present study investigates the mechanism of antiemetic action of cannabinoids in an established animal model of emesis, the least shew (Cryptotis parva). Since cannabinoid agonists prevent emesis, it was hypothesized that blockade of either the cannabinoid CB1 receptor or the cannabinoid CB2 receptor would induce vomiting. Thus, the emetic potential of SR 141716A (CB1 receptor antagonist) or SR 144528 (CB2 receptor antagonist) was investigated. Both intraperitoneal (0, 1, 2.5, 5, 10 and 20 mg/kg, n = 7–15 per group) and subcutaneous (0, 10, 20 and 40 mg/kg, n = 6–9 per group) administration of SR 141716A caused emesis (ED50 = 5.52 ± 1.23 and 20.2 ± 1.02 mg/kg, respectively) in the least shrew in a dose-dependent manner. Indeed, both the frequency of emesis and the percentage of animals vomiting increased with increasing doses of SR 141716A. Significant effects were seen at the 10- and 20-mg/kg doses for the IP route, while only the 40-mg/kg dose produced significant emesis via the SC route. The CB2 antagonist failed to produce emesis via either route of administration. SR 141716A at an IP dose of 20 mg/kg was used to induce emesis for drug interaction studies. Thus, varying doses of three different classes of cannabinoid agonists [CP 55, 940 (0, 0.1, 0.5 and 1 mg/kg), WIN 55, 212-2 (0, 1, 5 and 10 mg/kg), and Δ9-THC (0, 5, 10 and 20 mg/kg)], were administered IP to different groups of shrews 10 min prior to SR 141716A injection. The frequency of emesis was recorded for 30 min following the administration of SR 141716A. The order of potency for redcing both the frequency of emesis and the percentage of shrews vomiting was CP 55, 940 > WIN 55, 212-2 > Δ9-THC which is consistent with an action on the CB1 receptor. These results suggest that the antiemetic activity of Δ9-THC and its synthetic analogs reside in their ability to stimulate the cannabinoid CB1 receptor. Furthermore, the antiemetic potency of CP 55, 940 is 45 times greater than Δ9-THC. On the other hand, blockade of CB1 receptors can induce vomiting, which implicates an important role for endogenous cannabinoids in emetic circuits.

A review of dolasetron as management of nausea and vomiting in cancer patients

Objective. To systematically review the literature about the pharmacology, pharmacokinetics, efficacy, dosing, and adverse effects of dolasetron, and to define its role in the management of chemotherapy-and radiation-induced nausea and vomiting. Data Synthesis. A MedLine search was conducted using 5-HT3-receptor antagonists, antiemetics, chemotherapy toxicity, dolasetron, emesis, nausea, and vomiting as search terms. Reference lists and bibliographies of pertinent articles were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed. Data Synthesis. Dolasetron is a serotonin type 3 (5-HT3)-receptor antagonist with potent antiemetic effects in the management of nausea and vomiting. Following administration, dolasetron is rapidly converted to hydrodolasetron, which is believed to be responsible for the drug's antiemetic activity. Results of multiple studies have demonstrated the efficacy of this agent in the prevention of chemotherapy-induced emesis, including that induced by cisplatin. As a single agent, dolasetron produces a complete response rate (RR) in 44% to 57% of patients treated with cisplatin (≥70 mg/m2) and in 59% to 80% of patients treated with moderately emetogenic chemotherapy, such as cyclophosphamide, methotrexate, and fluorouracil (CMF) therapy. When combined with dexamethasone, the RRs are increased. Dolasetron is well tolerated, with headache (24%) and diarrhea (12%) the most commonly reported adverse effects. The efficacy and safety of dolasetron are comparable to those observed with other 5-HT3-receptor antagonists. According to four recently published clinical practice guidelines for use of antiemetics, dolasetron is an appropriate first-line option for the prevention of nausea and vomiting due to moderately to highly emetogenic chemotherapy. Further clinical trials will determine the optimal dose and the role of this highly effective antiemetic agent for other purposes, such as treatment of delayed emesis and emesis resulting from radiation therapy and high-dose chemotherapy followed by bone marrow transplantation.

Economics and health-related quality of life in antiemetic therapy: recommendations for trial design

Emesis (nausea and vomiting) is one of the most important toxicities associated with chemotherapy. Although it is not life threatening, it has a major impact on a patient's health-related quality of life (HRQL) and overall response to chemotherapy. New antiemetics are expensive and well-conducted comparative health economic studies are rare. The aim of the study was to review the literature in the area of chemotherapy-induced emesis in cancer patients and to offer recommendations for the inclusion of these outcomes in the design of clinical trials for new antiemetic therapies. The economic literature was reviewed based on methodological standards for economic evaluation. Many studies did not comply with standards, specifically with regard to the choice of alternatives, chosen perspective, setting, type of emesis, measurement of costs and defining outcomes (including health-related quality of life). These issues are described for each study and recommendations for trial design are presented. The role of economic data is to support decision making in choosing between competing antiemetic therapies. It is the combination of clinical outcomes, costs and health-related quality of life, which will allow treating physicians to comprehensively assess the relative value of antiemetic therapies and to provide the most cost-effective therapy for their patients.

History of the Development of Antiemetic Guidelines at Mayo Clinic Rochester

History of the Development of Antiemetic Guidelines at Mayo Clinic Rochester

A review of dolasetron as management of nausea and vomiting in cancer patients

A review of dolasetron as management of nausea and vomiting in cancer patients

Intravenous Itasetron: Establishing the Effective Dose Range for the Prophylactic Control of Acute Emesis in Cancer Patients Undergoing High-Dose Cisplatin Chemotherapy

Nausea and vomiting induced by chemotherapy are a major cause of distress to patients and reduce compliance with potentially beneficial treatment. Itasetron hydrochloride is a new 5-hydroxytryptamine3 (5-HT3) antagonist with potent antiemetic properties. It is more potent than ondansetron in animal models and in early clinical studies it demonstrates a long half-life and does not undergo hepatic biotransformation before elimination. The aim of this open, uncontrolled study was to establish the effective dose range of itasetron hydrochloride given intravenously (i.v.) to patients due to receive high-dose cisplatin chemotherapy (50–120mg/m2) for the first time. Thirty-nine patients were enrolled in the trial and received a single i.v. infusion of itasetron hydrochloride at a dose of 17–280μg/kg body weight before commencing the cisplatin infusion (median dose 90–110mg/m2). Antiemetic protection was demonstrated by doses in the range of 35–280μg/kg. The 17μg/kg dose was not effective. Treatment failure (>5 emetic episodes/24 hours) was reported in only six (16%) of the 38 evaluable patients over all treatment groups. Adverse events were generally mild or moderate and of a similar type and incidence to those of current 5-HT3 antagonists. Physicians' and patients' assessments of efficacy and tolerability of itasetron hydrochloride were similar, the majority rating the treatment as ‘good’ or ‘very good’. In conclusion, itasetron hydrochloride is effective in the dose range 35–280μg/kg in preventing cisplatin-induced emesis. Taken together with results from a larger dose-finding study, a dose corresponding to 35μg/kg (equivalent to 2.5mg itasetron, calculated as free base) has been pursued in Phase III studies with the i.v. formulation.

Comparison of an orally disintegrating ondansetron tablet with the conventional ondansetron tablet for cyclophosphamide-induced emesis in cancer patients: A multicenter, double-masked study

A total of 427 cancer patients receiving cyclophosphamide chemotherapy participated in this multicenter, double-masked, double-dummy, parallel-group, randomized study comparing the antiemetic efficacy and safety of an 8-mg conventional ondansetron tablet (OT, n = 212) taken twice daily with an 8-mg orally disintegrating ondansetron tablet (ODT, n = 215) taken twice daily for 3 days. In the primary efficacy analysis, complete or major control of emesis (0 to 2 emetic episodes) between days 1 and 3 was seen in 80% of OT and 78% of ODT patients. The 90% confidence interval for the differences between treatments was −8.6% to 4.4% (de fined interval of equivalence, ±15%), showing that the formulations were equivalent. In the secondary efficacy analysis, no significant differences were observed in the rates of complete control of emesis (no episodes of emesis) over 3 days (63% and 64% of the respective groups) and on day 1 (84% and 81%, respectively) and in the complete control of nausea over 3 days (37% and 43%, respectively) and on day 1 (59% and 61% of patients, respectively). The taste of ODT was acceptable to the majority of patients (89%) who received it. OT and ODT were both well tolerated. Thus 8 mg ODT twice daily represents a palatable, well-tolerated, and effective antiemetic treatment for the control of cyclophosphamide-induced emesis and nausea and provides equivalent treatment to OT 8 mg twice daily.

Randomized, double blind, dose-response trial across four oral doses of dolasetron for the prevention of acute emesis after moderately emetogenic chemotherapy

This double blind parallel group study assessed the acute antiemetic efficacy of four oral doses of dolasetron mesylate in cancer patients receiving their first course of intravenous chemotherapy with doxorubicin and/or cyclophosphamide. Patients were randomized to receive 25, 50, 100, or 200 mg of dolasetron mesylate 30 minutes prior to chemotherapy and were monitored for nausea and emetic episodes for the next 24 hours. Three hundred and nineteen cancer patients at 32 sites completed the study. Most patients were female (81%); of this group, 69% had breast carcinoma. A highly statistically significant linear trend demonstrating improved response with higher doses was detected for complete response (no emetic episodes and no rescue medication) (P < 0.001), for complete plus major response (0-2 emetic episodes and no rescue medication) (P < 0.001), and for patient visual analog scale assessments of nausea (P = 0.001) and general satisfaction with antiemetic therapy (P = 0.001). No serious adverse events were noted. The most frequent adverse event was mild, self-limiting headache, which has been reported with other drugs in this class. Single oral doses of dolasetron mesylate were found to be effective in preventing acute emesis in cancer patients receiving moderately emetogenic chemotherapy.

Marijuana to Prevent Nausea and Vomiting in Cancer Patients: A Survey of Clinical Oncologists

Marijuana, if rescheduled by the Drug Enforcement Agency, would be the only Food and Drug Administration (FDA)-approved drug to be administered by smoking. American physicians need timely, factual information about probable usage patterns and potential adverse effects of medical marijuana, and a factual complete review of the literature on the subject. We mailed a survey to 1,500 American clinical oncologists. Of particular interest was whether and how often in the past 24 months these physicians recommended smoked marijuana, synthetic tetrahydrocannabinol, or 5-HT3 (serotonin) antagonists (ondansetron [Zofran], granisetron [Kytril]) for their patients. We also inquired whether and how often the oncologists would prescribe marijuana in the form of cigarettes, were it to be FDA-approved. Completed surveys were received from 1,122 (75%) of the oncologists. The percentages of oncologists who prescribed or recommended selected antiemetics more than five times between 1992 and 1994 were 98% for 5-HT, antagonists, 6% for dronabinol (Marinol), and 1% for smoked marijuana. We also found that 332 (30%) of the oncologist-respondents to this nationwide survey supported rescheduling of marijuana for medical purposes; however, two thirds (67%) of the 332 respondents who were in favor of rescheduling estimated that they would write less than one prescription per month for marijuana cigarettes. A comprehensive literature review failed to provide persuasive evidence to recommend marijuana as a needed antiemetic medicine.

A double-blind, multicentre comparison of intravenous dolasetron mesilate and metoclopramide in the prevention of nausea and vomiting in cancer patients receiving high-dose cisplatin chemotherapy

The potent serotonin receptor (5-HT3) antagonists are new highly selective agents for the prevention and control of chemotherapy-induced nausea and vomiting that have been shown to be comparable to or more effective than traditional metoclopramide regimens. This study was designed to compare the antiemetic efficacy of dolasetron and metoclopramide in chemotherapy-naive and non-naive cancer patients receiving high-dose cisplatin-containing chemotherapy. This multicentre, double-blind, randomized trial compared the efficacy and safety of single i.v. doses of dolasetron mesilate salt (1.2 or 1.8 mg/kg) and metoclopramide (7 mg/kg) in 226 patients for the prevention of acute emesis and nausea associated with the administration of high-dose (≥80 mg/m2) cisplatin. Efficacy and safety were evaluated for 24 h. Complete responses were achieved by 57%, 48%, and 35% of patients given dolasetron mesilate 1.8 mg/kg (P=0.0009 vs metoclopramide), dolasetron mesilate 1.2 mg/kg (P=0.0058 vs metoclopramide), and metoclopramide, respectively. Overall, dolasetron was significantly more effective than metoclopramide for time to first emetic episode, nausea, patient satisfaction, and investigator global assessment of efficacy. Males, chemotherapy-naive patients, and alcoholics had higher response rates. Dolasetron was well tolerated, with mild-to-moderate headache most commonly reported. Twelve percent of patients receiving metoclopramide reported extrapyramidal symptoms compared with 0% of patients receiving dolasetron. In conclusion, dolasetron mesilate was effective for the prevention of CINV with high-dose cisplatin. Single i.v. doses of dolasetron mesilate were more effective than 7 mg/kg metoclopramide in preventing nausea and vomiting induced by highly emetogenic cisplatin-containing chemotherapy. In addition, 1.8 mg/kg dolasetron mesilate consistently produced the highest response rates and appears to be the most effective dose for further clinical development.

Serotonin mechanisms in chemotherapy-induced emesis in cancer patients.

Emesis is a common side effect of chemotherapeutic drugs. Cisplatin, nitrogen mustard and dacarbazine induce increases in urinary 5-hydroxyindoleacetic acid (5-HIAA) in parallel with the development of the period of emesis which is sensitive to 5-HT3 receptor antagonists ('acute emesis'). It is suggested that these cytotoxics release serotonin from enterochromaffin cells, which then acts on 5-HT3 receptors to trigger the emetic response. Cyclophosphamide, on the other hand, induces a modest emetic response, partly sensitive to 5-HT3 receptor antagonists, but not associated with increases in urinary 5-HIAA. It is suggested that cyclophosphamide-induced emesis is not mediated by the release of serotonin from enterochromaffin cells. Although after high-dose cisplatin most emesis is sensitive to 5-HT3 receptor antagonists, patients often present a milder, although more prolonged form of emesis which is mostly resistant to 5-HT3 receptor antagonists (also known as 'delayed emesis'). This form of emesis is not associated with increases in urinary 5-HIAA (not due to serotonin released from the enterochromaffin cells). Treatment with p-chlorophenylalanine (a serotonin synthesis inhibitor) inhibited cisplatin-induced emesis and cisplatin-induced increases in urinary 5-HIAA excretion. In summary, these results indicate that in human patients, serotonin plays a fundamental role in chemotherapy-induced emesis. Serotonin released from enterochromaffin cells seems to mediate emesis sensitive to 5-HT3 receptor antagonists induced by cisplatin, dacarbazine and nitrogen mustard. Emesis sensitive to 5-HT3 receptor antagonists associated with cyclophosphamide treatment, is not mediated by the release of serotonin from enterochromaffin cells by the cytotoxic. Therefore, cyclophosphamide could induce serotonin release either from enteric serotonin nerves or from the CNS. Cisplatin-induced emesis resistant to 5-HT3 receptor antagonists ('delayed emesis') is not mediated by serotonin released from enterochromaffin cells.

1227 Dose-response trial across four oral doses of dolasetron (DM) for emesis prevention after moderately emetogenic chemotherapy (CT)

This double-blind multicenter trial studied four oral doses of OM for antiemetic effectiveness in 319 predominately CT-naive cancer patients, receiving IV CT. Patients were randomized to one of four treatments: 25, 50, 100, or 200 mg of DM, 30 minutes prior to CT with doxorubicin (in combination: 25–75 mg/m2 or alone: ≥ 40 mg/m2) and/or cyclophosphamide (500–1200 mg/m2). Efficacy was compared across doses using complete response (CR: no emetic episodes [EE] and no escape medication [EM]); CR + major response (CMR: 1–2 EE and no EM); patients assessment of nausea < 5 mm = no nausea) and satisfaction with antiemetic therapy via a 100 mm visual analog scale (VAS). At 24 hours, statistically significant linear trends (P < 0.0001) were detected across the 25, 50, 100, and 200 mg doses of DM, respectively, for CR (31%, 34%, 49%, and 46%), for CMR (28%, 43%, 52%, 56%), and for CR + no nausea (20.5%, 26.5%, 37.5%, 39.7%). Lineartrends with dose were also statistically significant for patient assessment of nausea (P < 0.0006) and general satisfaction (P < 0.0009). No significant dose related trends in the incidence of headache or elevated transaminases were detected. Single oral doses of DM are effective in preventing emesis in cancer patients with excellent safety and efficacy recorded with both the 100 and 200 mg doses of dolasetron. This double-blind multicenter trial studied four oral doses of OM for antiemetic effectiveness in 319 predominately CT-naive cancer patients, receiving IV CT. Patients were randomized to one of four treatments: 25, 50, 100, or 200 mg of DM, 30 minutes prior to CT with doxorubicin (in combination: 25–75 mg/m2 or alone: ≥ 40 mg/m2) and/or cyclophosphamide (500–1200 mg/m2). Efficacy was compared across doses using complete response (CR: no emetic episodes [EE] and no escape medication [EM]); CR + major response (CMR: 1–2 EE and no EM); patients assessment of nausea < 5 mm = no nausea) and satisfaction with antiemetic therapy via a 100 mm visual analog scale (VAS). At 24 hours, statistically significant linear trends (P < 0.0001) were detected across the 25, 50, 100, and 200 mg doses of DM, respectively, for CR (31%, 34%, 49%, and 46%), for CMR (28%, 43%, 52%, 56%), and for CR + no nausea (20.5%, 26.5%, 37.5%, 39.7%). Lineartrends with dose were also statistically significant for patient assessment of nausea (P < 0.0006) and general satisfaction (P < 0.0009). No significant dose related trends in the incidence of headache or elevated transaminases were detected. Single oral doses of DM are effective in preventing emesis in cancer patients with excellent safety and efficacy recorded with both the 100 and 200 mg doses of dolasetron.

Dexamethasone improves the efficacy of granisetron in the first 24 h following high-dose cisplatin chemotherapy

The object of the study was to determine whether dexamethasone improved the efficacy of the serotonin receptor (5-HT3) antagonist granisetron in controlling acute (within 24 h) emesis in cancer patients receiving high-dose cisplatin chemotherapy and to ascertain whether continuation of granisetron after 24 h reduces the occurrence of delayed emesis. This randomised, double-blind, multicentre, three-arm study was conducted at 21 medical centres. A group of 292 nausea- and emesis-free patients with cancer, who had never had chemotherapy and were scheduled to receive at least 50 mg/m2 cisplatin, were given 3 mg granisetron i.v. in a 15-min infusion with or without 10 mg dexamethasone i.v. completed 5 min prior to high-dose cisplatin and 1 mg granisetron p.o. at +6 h and +12 h. Primary study end-points were control of emesis and nausea. Patients completed a self-report diary every 6 h for the first 24 h. At the end of the 24-h period, the patients who received dexamethasone had a significantly higher complete protection rate from emesis (64% compared to 39%) than those who received no steroid. Similarly, the dexamethasone-treated group had a significantly higher complete plus partial (0-2 emetic episodes) protection rate (84% compared to 64%). This study shows that dexamethasone markedly enhances the antiemetic efficacy of granisetron for acute-onset emesis in high-dose cisplatin chemotherapy.

On-demand tropisetron successfully treated emesis in cancer patients

On-demand tropisetron successfully treated emesis in cancer patients

The anti-emetic efficacy and tolerability of tropisetron in patients conditioned with high-dose chemotherapy (with and without total body irradiation) prior to bone marrow transplantation

Nausea and vomiting are among the most distressing side-effects of chemoradiotherapy. Conditioning protocols for patients undergoing bone marrow transplantation consist of highly emetogenic high-dose chemotherapy with or without total body irradiation. Marked improvement in controlling emesis and nausea was achieved by the introduction of a new class of antiemetic drugs, the 5HT3 serotonin-receptor antagonists. Tropisetron is a highly potent, selective antagonist of 5HT3 receptors. Previous studies have used a single 5-mg dose i.v. of tropisetron to control nausea and vomiting in cancer patients. The present study was undertaken to evaluate the efficacy and safety of a single daily dose of tropisetron in controlling emesis in patients receiving high-dose chemotherapy (with or without total body irradiation) prior to bone marrow transplantation. The anti-emetic efficacy was investigated in a non-homogeneous cohort in a prospective and open study. Of 11 patients evaluated, 9 (81%) showed complete or major control, 1 (9%) minor control and 1 (9%) failed to respond. The most common adverse events reported during the study included diarrhea (46%) and headache (18%), no patients being withdrawn because of side-effects. Our data suggest that a single 5-mg i.v. dose of tropisetron is safe and effective in preventing chemotherapy-induced emesis in patients receiving bone marrow transplantation conditioning. A larger randomized study is warranted to confirm our preliminary results.

Cardiovascular conditioning and anticipatory nausea and vomiting in cancer patients.

Explanations of individual differences in susceptibility to learning of anticipatory nausea and/or vomiting (AN/V) in cancer patients have focused mainly on the patients who develop AN/V. On the basis of conditioning theory, however, one would expect that all patients who experience post-treatment nausea and/or vomiting (PN/V) should develop AN/V. Consistent with findings demonstrating that conditioned responses are more easily established in autonomic-reactive individuals, we have previously reported that patients who do not develop AN/V (noAN/V) are less autonomic reactive than the AN/V patients. Thus, we hypothesized that the noAN/V patients might not show classical conditioning to the same degree and extent as the AN/V patients and that conditioning may be the mediating mechanism in AN/V. This study presents data from 36 patients. Among the 28 patients who experienced PN/V, 16 developed AN/V. We found no systematic group differences in severity of PN/V or antiemetic treatment. Before chemotherapy, all patients were tested in a signaled reaction-time paradigm. We used two different tones (CSs), one of which was always followed by a noise (UCS) as a button-press signal. The patients who later developed AN/V demonstrated significantly shorter reaction times, and also showed enhanced cardiovascular reactivity to the tone followed by the UCS (CS+) in comparison with the nonsignal tone (CS-). The noAN/V patients did not show differential cardiovascular responses to the CS+ and CS-.