Assessment of the emetogenic potential of intrathecal chemotherapy and response to prophylactic treatment with ondansetron

 The purpose of this study was to document the emetogenic potential of intrathecal chemotherapy (IC) in children and to evaluate the efficacy of ondansetron in reducing nausea and vomiting with this chemotherapy treatment. Patients less than 18 years of age with acute lymphoblastic leukemia were eligible to participate in a survey project measuring the emetogenic potential of various chemotherapy treatments. Patients surveyed for 1 or more IC treatments were included in this report. The IC consisted of methotrexate, hydrocortisone and cytarabine, dosed according to patient age. A nausea/vomiting survey instrument was completed by each patient and/or parent following IC treatment. The instrument rated nausea, vomiting and daily activity interference (DAI) on a 4-point scale of 0=none, 1=mild, 2=moderate and 3=severe, and collected data on the number of vomiting and/or retching episodes in addition to the child's appetite following the chemotherapy treatment. When ondansetron was employed, it was administered in an i.v. infusion at a dose of 0.15 mg/kg before and after chemotherapy or as an oral dose of 4 mg or 8 mg before chemotherapy. Courses of IC without antiemetics were analyzed to determine the emetogenic potential of IC. For patients receiving IC both with and without ondansetron, courses were compared with each patient used as their own control to determine the influence of ondansetron upon survey responses. Statistical analysis consisted of nonparametric Friedman 2-way ANOVA for ordinal variables and a paired t-test for continuous variables. The binomial test was employed to analyze for differences between ondansetron and no antiemetic in the number of patients with complete control of both nausea and vomiting or vomiting alone. A total of 63 children with a mean age of 7.6±4.2 years were each studied on one or more occasions. Thirty-seven children were surveyed for 87 IC treatments without antiemetics (group I), and 17 children from this group were surveyed for 48 IC courses with i.v. ondansetron (group IA). An additional 18 children were subsequently surveyed for 39 IC courses with i.v. ondansetron (group II). Fifteen patients (7 of whom were members of group I) were surveyed following 33 IC courses with oral ondansetron (group III). The survey scores for group I patients were: nausea severity 1.3±1.1, vomiting severity 1.2±1.1, DAI 1.2±1.0 and mean number of emetic episodes 4.7±8.4. The mean appetite score was 1.5±1.1. For patients in group IA, nausea severity (0.8±0.9), vomiting severity (0.5±0.8), DAI (0.7±0.8), and the number of emetic episodes (1.4±2.8) were all significantly lower than with prior IC treatments without ondansetron. For complete protection, children receiving i.v. ondansetron had greater complete protection rates from both nausea and vomiting or vomiting alone than did patients receiving no antiemetic. Survey responses were also lower for patients receiving oral ondansetron, but insufficient control data did not allow for statistical analysis. IC results in mild to moderate nausea and vomiting in children. The emetogenic potential of IC is significantly reduced by i.v. ondansetron.     

An open-label dose comparison study of ondansetron for the prevention of emesis associated with chemotherapy prior to bone marrow transplantation

Nausea and vomiting are significant side effects in bone marrow transplant (BMT) patients who receive high-dose preparative regimens. Higher than conventional ondansetron doses and continuous infusion might improve emetic control, because of the high doses and combinations of chemotherapy (CT) used in this setting. Our objective was to conduct a prospective, randomized study comparing two different administration methods of high-dose ondansetron during a BMT preparative regimen in breast cancer patients. Patients were eligible if they were nonpregnant women over 18 but under 65 years of age, undergoing highly emetogenic CT in preparation for autologous BMT. All patients received ondansetron as an intermittent (INT=24 mg i.v. q 12 h/day) or continuous intravenous infusion (CIV=8 mg i.v. loading dose followed by a continuous infusion of 2 mg/h per day). A total of 66 patients were enrolled in the study (n=34, INT; n=32, CIV). There was no statistical difference between treatment groups in the worst grade of emesis for the entire study period (P=0.49). Greater than 90% of all patients were graded as failures (≥5 emetic episodes or need for rescue antiemetics). Complete control (no vomiting episodes) and complete plus major control (1–2 emetic episodes) per day ranged from 8% to 85% and 11% to 91%, respectively. There was no significant difference between the treatment arms in: grade of emesis, episodes of vomiting and retching, nausea scores, and mean number of rescue medications administered. There were no differences in efficacy when high-dose ondansetron was given as CIV or INT for the control of nausea and vomiting in breast cancer patients undergoing high-dose CT for autologous BMT. Ondansetron alone was not adequate to provide sustained control of CT-induced nausea and vomiting over the entire 5-day study period. A combination of antiemetics targeting various mechanisms of CT-induced nausea and vomiting may be necessary to improve response rates.     

Assessing the impact of chemotherapy-induced nausea and vomiting on patients' daily lives: a modified version of the Functional Living Index—Emesis (FLIE) with 5-day recall

Background The Functional Living Index—Emesis (FLIE), a patient-reported outcome measure, was originally developed to assess the impact of chemotherapy-induced nausea and vomiting (CINV) on patients' daily lives over the 3 days following chemotherapy. More recent studies of CINV include assessments covering the 5 days following chemotherapy in an effort to capture information during both the acute (within 24 h) and delayed (up to 5–7 days) phases of CINV.Goals To assess the measurement characteristics of a modified version of the FLIE with 5-day recall. Instrument reliability, validity, and missing data were assessed.Patients and methods Data were collected from 183 patients receiving cisplatin 70 mg/m² as part of a phase IIb antiemetic trial of an NK-1 receptor antagonist (MK-0869). Patients recorded the number of vomiting episodes and nausea ratings in a 5-day daily diary.Results The 5-day FLIE had: (1) excellent internal consistency within FLIE Nausea and Vomiting domains (Cronbach's alpha 0.77–0.78), (2) acceptable construct validity shown by FLIE item-total correlations stronger within domains (r=0.74–0.97) than across domains (r=0.52–0.76), and (3) acceptable convergent validity as shown by moderate to strong correlations between FLIE domain scores and independent endpoints of emetic episodes, nausea ratings, and use of rescue medications. The extent of missing data was within acceptable limits with less than 2% of patients missing data.Conclusion The 5-day FLIE had adequate measurement characteristics for studying the impact of CINV on patients' daily lives during the period covering both the acute and delayed phases.     

Emetic potential of daily oral etoposide

Background Chemotherapeutic agents are classified by their degree of emetogenicity. Highly and moderately emetogenic agents require antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. Intravenous etoposide is listed as having low emetic potential. However, oral etoposide is categorized as having moderate emetogenicity. Daily oral etoposide is used in refractory germ cell cancer patients. We prospectively evaluated the emetic potential of oral etoposide in this patient population.Materials and methods Between August 2003 and February 2006, 16 patients with refractory germ cell cancer received single-agent, daily oral etoposide 50 mg/M² for 21 consecutive days every 4 weeks. All patients had progressed after cisplatin combination chemotherapy and had received high-dose chemotherapy with carboplatin plus etoposide (intravenously) with peripheral blood stem cell transplant. No patient received prophylactic antiemetics. Patients completed a six-question Multinational Association of Supportive Care in Cancer (MASCC) antiemetic tool during each day of etoposide during the first 21-day course. Nausea intensity and duration were recorded. Number of emetic episodes and any antiemetic medications were recorded.Results All 16 patients completed the six-question MASCC form. Eleven of 16 had no nausea or vomiting and two other patients had only minimal nausea, despite absence of any prophylactic antiemetics. Only two patients required antiemetic support. Two patients experienced emesis for a single episode. One patient had nausea on days 9–20 with a MASCC rating of 3–6, and one patient had continued mild nausea (MASCC rating 1–3) for all 21 days.Conclusions Daily oral etoposide has a low probability of producing chemotherapy-induced nausea and/or vomiting and, in our opinion, does not require prophylactic antiemetics.     

Granisetron plus dexamethasone in moderately emetogenic chemotherapy: evaluation of activity during three consecutive courses of chemotherapy

In this study we evaluated the antiemetic activity of a combination of 3 mg granisetron in a short i.v. infusion followed by 12 mg dexamethasone i.v. in 64 patients with cancer receiving moderately emetogenic chemotherapy scheduled in a single day. No patient had previously undergone chemotherapy and three consecutive cycles were evaluated. Response to antiemetic treatment was graded as follows: complete response, no episodes of vomiting; major response, only one episode; minor response, two to four episodes; failure, more than four episodes. Nausea was graded as absent, mild, moderate or severe (patients bedridden). At the first cycle a complete protection from acute vomiting and nausea was achieved in 95% and 73% of patients respectively; the rate of complete response for delayed vomiting was 90%, while 45% of patients complained of delayed nausea. The antiemetic and antinausea efficacy remained substantially unchanged during the second and third cycles of chemotherapy. Constipation and headache were the most frequent adverse events. In conclusion this antiemetic regimen appears very effective in preventing nausea and vomiting in moderately emetogenic chemotherapy.     

Effect of postchemotherapy nausea and vomiting on health-related quality of life

The purpose was to measure the effects of postchemotherapy nausea and vomiting (PCNV) on health-related quality of life (HQL) in patients receiving either moderately or highly emetogenic chemotherapy. The study sample consisted of 832 chemotherapy-naive patients with cancer who received either moderately or highly emetogenic chemotherapy as part of multicenter trials of new antiemetics. The patients completed the self-report European Organization for Research and Cancer (EORTC) core Quality of Life Questionnaire (QLQ-C30) before chemotherapy (baseline) and 1 week (day 8) and 2–4 weeks after chemotherapy. They also completed a self-report nausea and vomiting (NV) diary for 5–7 days after chemotherapy. To determine the effects of PCNV on HQL, the change in scores between the baseline and day 8 HQL assessments was calculated for each domain and symptom in the QLQ-C30 and compared in four subgroups of patients: those with both nausea and vomiting, those with nausea but no vomiting, those with no nausea but with vomiting, and those with neither nausea nor vomiting. The group with both nausea and vomiting showed statistically significantly worse physical, cognitive and social functioning, global quality of life, fatigue, anorexia, insomnia and dyspnea as compared to the group with neither nausea nor vomiting (0.0001<P<0.05). Patients with only nausea but no vomiting tended to have less worsening in functioning and symptoms than those having both nausea and vomiting. Increased severity of vomiting (>2 episodes) was associated with worsening of only global quality of life and anorexia as compared with 1–2 episodes of vomiting (0.0001<P<0.01). By 2–4 weeks after chemotherapy all HQL scores had either returned to their baseline levels or were better than baseline. PCNV adversely affects several quality-of-life domains, but patients with only nausea experience less disruption than do those with both nausea and vomiting. Patients with 1–2 episodes of vomiting experience almost the same degree of disruption of HQL as do patients with more than 2 episodes of vomiting.     

肿瘤化疗所致恶心呕吐现状调查

目的调查化疗所致恶心呕吐（chemotherapy—inducednauseaandvomiting,CINV）的患者心理预期和发生情况,并评估CINV对患者生活质量的影响,为提高临床医生对CINV的认识和重视提供依据。方法采用问卷调查的方式,调查华中科技大学同济医学院附属同济医院使用中度致吐风险化疗（MEC）或高度致吐风险化疗（HEC）的患者,并对其进行连续两周期相同化疗方案的随访。患者分别于化疗开始前、化疗第2天和化疗第6天,记录化疗期间急性、延迟性恶心呕吐发生情况、自主止吐用药和CINV对生活功能的影响,调查结果采用描述性分析和多元线性回归分析。结果本研究共调查344例患者,最终303例患者完成问卷调查。结果显示：单日化疗MEC组急性、延迟性和总的完全缓解率分别为86．1％、76．6％和71．5％,HEC组为84．1％、71．0％和66．7％。多日化疗患者分别为93．8％、64．9％和64．9％;第2周期化疗前患者关于恶心呕吐预期值和焦虑值与患者前一周期化疗延迟性恶心发生的严重程度密切相关;约30％的患者因CINV对生活功能造成负面影响。结论在行中度和高度致吐风险化疗的患者中,CINV治疗现状仍存在较大问题,尤其是在延迟期反应和恶心症状的控制方面。在临床实践中需进一步加强对CINV的关注,并提供更加有效的治疗措施。     

Effectiveness of a single-day three-drug regimen of dexamethasone, palonosetron, and aprepitant for the prevention of acute and delayed nausea and vomiting caused by moderately emetogenic chemotherapy

Purpose

Chemotherapy-induced nausea and vomiting includes both Acute (0–24 h) and Delayed (24–120 h) components with different physiologic mechanisms. A combination of a serotonin antagonist, a corticosteroid, and an NK-1 antagonist has proven effective against this problem. However, standard antiemetic regimens require administration over 3–4 days after chemotherapy. The present study evaluated a more convenient single-day three-drug antiemetic regimen for patients receiving moderately emetogenic chemotherapy.

Materials and methods

Chemotherapy-naïve patients with solid tumors receiving cyclophosphamide and/or doxorubicin were eligible. Patients could not have pre-existing etiologies for vomiting. Prior to chemotherapy, patients received a single dose of aprepitant 285 mg p.o., dexamethasone 20 mg p.o., and palonosetron 0.25 mg i.v. A daily patient diary recording episodes of emesis and severity of nausea was then kept for 5 days. Any further antiemetics were considered rescue medication.

Results

Forty-one eligible and evaluable patients (40 women, one man) with breast cancer were entered on study. Most were receiving adjuvant chemotherapy. Complete Response (no vomiting, no rescue medication) was seen in 51% of patients, including 76% with Complete Response for the Acute period and 66% for the Delayed period. No emesis was reported for 100% of patients in the Acute period and 95% in the Delayed period. No Nausea was seen in 32% of patients. No untoward toxicities were seen.

Conclusion

A single-day three-drug antiemetic regimen is feasible and effective for protection against both Acute and Delayed vomiting after moderately emetogenic chemotherapy. Formal comparison to a standard multi-day antiemetic regimen is warranted.     

Emesis in patients receiving acupuncture,sham acupuncture or standard care during chemo-radiation: A randomized controlled study

ObjectiveTo study nausea, vomiting and need for rescue antiemetics in patients receiving antiemetic acupuncture, sham acupuncture or standard care during concomitant chemotherapy during pelvic radiotherapy.MethodsIn total, 68 patients participated (75% women, mean age 56 years, 53% had gynecological, 43% colorectal, and 4% other cancer types). Fifty-seven of them were blinded randomized to verum (n = 28) or sham (n = 29) acupuncture, median 10 sessions. During the study period of four weeks, the patients daily registered their nausea, vomiting and consumption of antiemetics. They were compared to a reference group (n = 11) receiving standard care only, who delivered these data once (after receiving mean 27 Gy radiotherapy dose).ResultsMore patients in the sham acupuncture group (17 of 20; 85%, p = 0.019, RR 1.81, CI 1.06–3.09) consumed antiemetics, compared to the verum acupuncture group (8 of 17; 47%). In the standard care group, 7 of 11 (63%) consumed antiemetics. The verum acupuncture treated patients experienced lower intensity of nausea than the other patients (p = 0.049). There was a non-significant tendency that more patients receiving either sham acupuncture or standard care experienced nausea (21 of 31; 68%) than patients receiving verum acupuncture (9 of 17; 53%: p = 0.074, RR 1.58, CI 0.91–2.74).ConclusionPatients treated with verum acupuncture needed less antiemetics and experienced milder nausea than other patients. Our study was small and many analyses lacked statistical power to detect differences; we welcome further sham-controlled efficacy studies and studies regarding the role of non-specific treatment components for experiencing antiemetic effects of acupuncture.     

Antiemetics in children receiving cancer chemotherapy

Nausea and vomiting are debilitating side effects that often accompany the administration of chemotherapy and may lead to adverse physiological and psychological effects. Chemotherapy agents usually stimulate the chemoreceptor trigger zone, which then sends signals to the vomiting center in the medullary lateral reticular formation. The neurochemistry of vomiting involves serotonin and serotonin S3 receptors. Nausea and vomiting are difficult to treat once they have occurred, and prior poor antiemetic control may lead to future anticipatory nausea and vomiting. Thus, good antiemetic regimens must be prophylactic, scheduled, and individualized. Specific regimens must be adjusted to account for the emetogenic potential of the chemotherapy drug(s) being administered and the individual patient's preferences. The major classes of antiemetics include serotonin S3 receptor antagonists, phenothiazines and metoclopramide. Steroids are ineffective antiemetics alone but good potentiators of other antiemetics. We usually recommend a serotonin S3 receptor antagonist alone for less emetogenic regimens or in conjunction with dexamethasone for more emetogenic regimens. For breakthough vomiting, we usually add lorazepam and/or scopolamine.Presented as an invited lecture at the 6th International Symposium: Supportive Care in Cancer, New Orleans, La., USA, 2–5 March 1994     

The Effects of Peppermint Oil on Nausea,Vomiting and Retching in Cancer Patients Undergoing Chemotherapy: An Open Label Quasi–Randomized Controlled Pilot Study

ObjectivesThe current study evaluated the effects of peppermint oil on the frequency of nausea, vomiting, retching, and the severity of nausea in cancer patients undergoing chemotherapy.DesignA quasi-randomized controlled study.SettingPatients were recruited from the ambulatory chemotherapy unit of a public hospital located (Batman, Turkey) between September 2017 and September 2018.InterventionsThe participants in the intervention group applied one drop the aromatic mixture on the spot between their upper lip and their nose, three times a day for the five days following chemotherapy administration, in addition to the routine antiemetic treatment. Participants in the control group underwent only the routine antiemetic treatment. Main outcome measures VAS-the severity of nausea and the Index of Nausea, Vomiting, and Retching.ResultsThe VAS nausea score was significantly lower after peppermint oil applying in the patients receiving Folfirinox (treatment effect (mean dif.): 4.00±2.28; P<0.001), Paclitaxel-Trastuzumab (treatment effect (mean dif.): 1.70±0.90; P=0.014), Carboplatin-Paclitaxel (treatment effect (mean dif.): 3.71±1.41; P<0.001), and Cyclophosphamide-Adriamycin (treatment effect (mean dif.): 1.41±0.73; P=0.005) excluding cisplatin scedule (treatment effect (mean dif.): 0.56±2,18; P=0.642). We detected a statistical significant difference in the change in frequency of nausea, vomiting, retching in the other all schedules excluding cisplatin schedule (P<0.05).ConclusionsThe peppermint oil was significantly reduced the frequency of nausea, vomiting, retching and the severity of nausea in cancer patients undergoing chemotherapy. Therefore, usage of peppermint oil together with antiemetics after chemotherapy with moderate and low emetic risk may be recommended to cope with CINV.     

Acupuncture against chemotherapy-induced nausea and vomiting in pediatric oncology

GOALS: In this multicenter crossover study, our aim was to evaluate the efficacy and acceptance of acupuncture as a supportive antiemetic approach during highly emetogenic chemotherapy in pediatric oncology. PATIENTS AND METHODS: Eleven children receiving several courses of highly emetogenic chemotherapy for treatment of solid tumors were included. Randomization allocated patients to start chemotherapy either with antiemetic medication plus acupuncture or antiemetic medication alone. During all study courses, patients continued to receive their programmed and additional antiemetic medication as needed. Acupuncture was given at day 1 of chemotherapy and at subsequent days on patient's demand. The amount of baseline and additional antiemetic medication during chemotherapy was documented. Patients maintained a daily diary of vomiting episodes and completed an evaluated nausea score at the end of every course. Their body weight was taken before and after a chemotherapy course. MAIN RESULTS: Twenty-two courses with or without acupuncture were compared. The benefits of acupuncture in adolescents with respect to the reduction of additional antiemetic medication were observed. Acupuncture enabled patients to experience higher levels of alertness during chemotherapy and reduced nausea and vomiting. Except for needle pain, no side effects were noted. Patient's acceptance of acupuncture was high. CONCLUSION: Our data indicate that acupuncture might reduce antiemetic medication and episodes of vomiting in pediatric oncology.     

Antiemetic efficacy of combination therapy with granisetron plus prednisolone plus the dopamine D2 antagonist metopimazine during multiple cycles of moderately emetogenic chemotherapy in patients refractory to previous antiemetic therapy

 Effective antiemetic treatment of patients who have previously experienced chemotherapy-induced nausea and vomiting is difficult. The aim of this study was to evaluate the antiemetic efficacy of a single intravenous dose of granisetron plus a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day in patients refractory to previous antiemetic treatment with granisetron or with prednisolone plus metopimazine. The study population was made up of 25 consecutive women with stage I or II breast cancer, who were treated with multiple cycles of adjuvant cyclophosphamide, fluorouracil plus methotrexate or cyclophosphamide, epirubicin plus fluorouracil given i.v. every 3 weeks. Patients received the three-drug combination of antiemetics during a total of 113 cycles of chemotherapy. No emetic episodes were reported in 88.9% cycles on day 1, in 94.7% cycles on days 2 through 5 and in 85.8% cycles on days 1 through 5 after chemotherapy. No nausea was reported in 43.4% cycles on day 1, in 49.6% cycles on days 2 through 5 and in 34.5% cycles on days 1 through 5. Nineteen patients (76.0%) completed the scheduled nine cycles of chemotherapy, 1 being withdrawn because of ≥5 emetic episodes and 5, because they were not satisfied with the antiemetic treatment. The treatment was well tolerated. In conclusion, granisetron plus prednisolone plus metopimazine is a highly effective antiemetic treatment in patients receiving moderately emetogenic chemotherapy refractory to antiemetic therapy with granisetron or prednisolone plus metopimazine. Published online: 25 February 2000     

Effect of acupressure on chemotherapy-induced nausea and vomiting in gynecologic cancer patients in Turkey

PurposeThe aim of the current study was to assess the effect of acupressure applied to the pericardium 6 (P6 or Neiguan) acupuncture point with a wristband (Sea-Band™) on nausea–vomiting in addition to the standard antiemetic medications used to prevent nausea–vomiting due to chemotherapy in gynecologic cancer patients.MethodIn this prospective research we used pre- and posttests. The study consisted of 34 patients with gynecologic cancer.ResultsWe found a significant decrease in the patients' mean scores of nausea and the use of antiemetic medications following acupressure applied to the patients with a wristband, when compared with their mean scores of nausea and the use of antiemetic medications prior to the application (p < 0.05), and we also observed a decline in their mean scores of vomiting and retching episodes; however, this decline was not found to be statistically significant (p > 0.05).ConclusionsThe findings from this study suggest that the acupressure applied to P6 acupuncture point with wristbands may be effective in reducing chemotherapy-related nausea and may decrease the antiemetic use after chemotherapy. Further research with more subjects is needed.     

Skipping day 2 antiemetic medications may improve chemotherapy induced delayed nausea and vomiting control: results of two pilot phase II trials

Background 5HT-3 antagonists and corticosteroids control less than 50% of delayed chemotherapy induced nausea and vomiting (CINV) episodes. Materials and methods Two pilot phase II studies were conducted at our institution in which all patients received ondansetron 16 mg and dexamethasone 20 mg before highly and moderately emetogenic chemotherapy on day 1. Patients on study 1 received metoclopramide 10 mg PO q8 h, granisetron 0.5 mg PO QD and dexamethasone 8 mg QD on days 2 and 3, whereas only metoclopramide was continued on the same schedule on day 4. On study 2, patients received the same medications, but no drugs were given on day 2, and the same treatment schedule was given to them but from days 3 to 5 instead. Patients were interviewed on days 1 and 6. Results Twenty-one patients participated on each study. There were no significant clinical differences between these two studied populations. Complete CINV control occurred from days 2 to 5 in 23.1% (95% CI: 8 to 47%) on study 1 vs 61.9% (95% CI: 38 to 81%) of the patients on study 2. By logistic regression, complete CINV control was correlated significantly with antiemetic treatment group (p=0.011) even when we considered only patients who achieved complete CINV control during the first 24 h (p=0.031). Conclusions Skipping day 2 antiemetic medications does not seem to worsen delayed CINV control and may even improve it, perhaps by avoiding tachyphylaxis to these medications. A randomized controlled study is in progress to confirm these results.     

Emesis induced by low or minimal emetic risk chemotherapy

For patients treated with low or minimally emetogenic chemotherapy there is little evidence from clinical trials supporting the choice of a given antiemetic therapy or of any treatment at all. The panel recognized the necessity of considering the introduction into clinical practice of new agents in these categories, particularly oral cytotoxic agents and targeted biological agents and also the possibility of over-treatment with antiemetics. There was consensus among panel members regarding the recommended treatment for patients receiving chemotherapy agents with low and minimal emetic risk. Patients without a history of nausea and vomiting for whom minimally emetic risk chemotherapy is prescribed should not routinely receive antiemetic prophylaxis. A single agent such as a low-dose corticosteroid is suggested for patients receiving agents of low emetic risk. If nausea and vomiting occurs during subsequent cycles of chemotherapy, prophylaxis with a single agent such as a substituted benzamide, a corticosteroid, or a phenothiazine should be administered. Only patients with persistent nausea and vomiting despite treatment with these recommended agents should receive a 5-HT3 receptor antagonist in the following cycles.     

Computerized system for outcomes-based antiemetic therapy in children

OBJECTIVE: To introduce a computerized data collection system used for an outcomes-based approach to antiemetic therapy in children, and to present data collected with this system in support of a new antiemetic dosing regimen. METHODS: A validated nausea/vomiting survey was used to collect data on nausea severity (NSEV), vomiting severity (VSEV), daily activity interference (DAI), and the number of vomiting episodes. NSEV, VSEV, and DAI were rated as 0 = none to 3 = severe. All children and/or their parents were surveyed following the completion of each highly emetogenic chemotherapy regimen. This survey was computerized and transferred to a handheld data entry unit. Time and motion studies were performed to compare the time required to collect nausea/vomiting data and transfer the data to a computerized database with the hand-held system versus traditional paper (manual) surveys. The hand-held technology was used to collect survey data for children receiving a new antiemetic regimen (daily ondansetron and dexamethasone [OD]), which was then compared with data obtained with a previously employed regimen (thrice-daily ondansetron and daily methylprednisolone [OM]). Statistical analysis and a cost-effectiveness analysis (CEA) were performed to compare the two antiemetic regimens. RESULTS: The mean time required for total data entry with the manual system was 5.2 minutes per survey versus 2.4 minutes with the hand-held technology (p = 0.0026). A total of 376 nausea/vomiting surveys in 78 children receiving the OM antiemetic regimen were compared with 153 surveys in 38 children treated with the OD regimen. The mean survey scores were as follows: NSEV (1.2 vs. 0.8), VSEV (1.0 vs. 0.7), DAI (1.0 vs. 0.7), and number of vomiting episodes (4.3 vs. 2.1) for OM and OD, respectively; all were significantly lower with the OD regimen (p < 0.05). The percentage of patients with complete control of nausea and vomiting (19.2% vs. 39.2%) and good control (55.6% vs. 65.4%) were significantly greater with the OD regimen (p < 0.05). The CEA revealed that the OD resulted in a reduction of approximately $31 per patient for good protection and a $258 reduction for complete protection from nausea and vomiting. CONCLUSIONS: A computerized outcomes-based system aided by handheld technology allowed for more prompt and efficient collection of nausea/vomiting data. The OD antiemetic regimen was shown to be a more cost-effective alternative for children receiving severely emetogenic chemotherapy.     

Superiority of methylprednisolone sodium succinate over low dose metoclopramide hydrochloride in the prevention of nausea and vomiting produced by cancer chemotherapy

Methylprednisolone sodium succinate and metoclopramide were compared for their efficacy, tolerance, and safety in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy in patients with cancer. Previously untreated patients about to receive at least 2 cycles of identical chemotherapy were entered into a study using a randomized, double-blind, crossover design. Patients were given either 250 mg of methylprednisolone or 10 mg of metoclopramide intravenously before the first cycle of chemotherapy and were then crossed over to receive the alternate medication before the second cycle of chemotherapy. Prochlorperazine was prescribed in both cycles for postchemotherapy nausea and vomiting. After each treatment cycle patients recorded the degree of nausea, drowsiness and anxiety, the number of episodes of vomiting experienced, and the amount of prochlorperazine taken. After the second treatment cycle patients recorded their preference for either the first or the second antiemetic medication with respect to nausea, vomiting, and overall effectiveness. Of 157 patients entered into the study, 115 were fully appraisable. Methylprednisolone was superior to metoclopramide in preventing nausea and vomiting and in decreasing anxiety and the amount of prochlorperazine used. A majority of the patients expressing a preference preferred methylprednisolone to metoclopramide for control of nausea (p = 0.003), control of vomiting (p = 0.0006), and overall effectiveness (p = 0.00004). There were few side-effects. We conclude that methylprednisolone may have some utility as an antiemetic in patients receiving moderately emetogenic chemotherapy, and who are treated as outpatients.     

Oral ondansetron is highly active as rescue antiemetic treatment for moderately emetogenic chemotherapy: results of a randomized phase II study

Aims  In the present phase II randomized study, two different schedules of ondansetron were investigated as rescue antiemetic treatment for delayed emesis related to moderately emetogenic chemotherapy (MEC). Materials and methods  Patients scheduled to receive a first course of MEC were randomized to ondansetron 8 mg intramuscularly (arm A) or ondansetron 16 mg orally (arm B) as rescue antiemetic treatment for delayed emesis. Efficacy and safety evaluation was performed from days 2 to 6 through the administration of a diary plus a questionnaire in which the emetic episodes and the use of the assigned rescue treatment were recorded. All patients received standard prophylaxis for delayed emesis with oral dexamethasone 8 mg daily for 4 days starting on day 2. Results  Eighty-nine patients were enrolled into the study, of whom 44 were randomized to arm A and 45 to arm B. Twenty-two patients in each arm developed grade 1–2 delayed nausea/vomiting, all of which recurred to the rescue study treatment. Oral ondansetron resulted superior to intramuscular ondansetron in terms of complete response for nausea (77.3% vs 40.9%, respectively, p = 0.01) and vomiting (81.8% vs 31.8%, respectively, p = 0.001). Both schedules resulted to be very well tolerated, and no differences in toxicity were observed between the two arms of treatment. Furthermore, personal satisfaction about the use of the assigned rescue study medication was significantly higher in arm B. Conclusions  Due to its high efficacy and excellent tolerability, oral ondansetron is an important option in the management of MEC-related delayed emesis refractory to standard antiemetic prophylaxis.     

Midazolam for acute emesis refractory to dexamethasone and granisetron after highly emetogenic chemotherapy: a phase II study

Goals of the work To assess whether the addition of midazolam to dexamethasone and granisetron could ameliorate the refractory acute nausea and/or vomiting caused by a highly emetogenic platinum-based chemotherapy.Patients and methods Enrolled in the study were 30 consecutive adult patients with refractory acute emesis. Nausea and vomiting were assessed by physicians and graded according to the NCI common toxicity criteria. Nausea was further self-assessed by patients using a visual analogue scale. Statistical analysis was performed by nonparametric tests.Results With the introduction of midazolam, 73% of patients had a reduction of at least one grade in nausea and vomiting intensity in comparison with the previous cycle of chemotherapy. From the second cycle, six patients (23%) had complete control of acute vomiting, a benefit that usually persisted in the subsequent cycles. Five more patients achieved complete control of acute vomiting during the third course; this effect persisted in the subsequent courses as well. The average relative reduction in acute nausea and vomiting grade from the first to the second course was 48% (95% CI 34–62%) and 48% (95% CI 31–65%), respectively. A significant difference in acute nausea and vomiting over all the six courses of chemotherapy administered was recorded (Friedman ANOVA, P <0.0001). Comparing each course with any subsequent course, a significant reduction in acute nausea and vomiting was observed between the first and second course, the first and third course, and the first and fourth course.Conclusions Our results suggest that midazolam may be a useful adjunct to standard antiemetic drugs for patients receiving highly emetogenic cisplatin-based chemotherapy. A randomized trial is warranted to confirm these results.