The impact of postchemotherapy nausea and vomiting on quality of life after moderately emetogenic chemotherapy

The purpose of the study was to assess the impact of postchemotherapy nausea and vomiting (PCNV) after moderately emetogenic chemotherapy on health-related quality of life (HRQOL) in patients with cancer being treated in a routine clinical practice setting. The European Organization for Research and Treatment in Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) was administered on day 2 and day 6 following moderately emetogenic chemotherapy to 119 patients with a variety of cancers. Patients kept daily diaries to record the occurrence and severity of nausea and vomiting. The QLQ-C30 questions were modified, for this study only, to assess the impact of nausea and vomiting on HRQOL in patients who experienced nausea and/or vomiting during the six days following chemotherapy. Those patients who experienced either nausea or vomiting experienced a decrease in HRQOL from prechemotherapy levels on six functioning and five symptom scales at day 2, and on four functioning and four symptom scales on day 6. Comparison of mean scores between the unmodified QLQ-C30 and the nausea and vomiting versions demonstrated that the HRQOL rating attributed to nausea and vomiting accounted for much, but not all, of the deterioration in HRQOL scores in patients who experienced these symptoms. It can be concluded that patients who experience PCNV experience a significant negative impact on their HRQOL and that this impact can be attributed in large part to their experience of nausea and vomiting. However, since not all of the deterioration is attributable to these symptoms, other reasons for some of the decrease in HRQOL must also be identified in future studies.     

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.     

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.     

Evaluation of Risk Factors Predicting Chemotherapy-Related Nausea and Vomiting: Results From a European Prospective Observational Study

ContextDemographic, personal, clinical, and behavioral factors predicting chemotherapy-induced nausea and vomiting (CINV) have been assessed in the past, but inconsistencies exist in the literature, studies have methodological shortcomings, and many risk factors have been examined in cross-sectional studies and univariate analyses.ObjectivesTo evaluate the predictive power of personal and treatment-related characteristics in the development of CINV, using a large and prospectively evaluated sample of a heterogeneous group of cancer patients receiving routine chemotherapy.MethodsThis was a multicountry, multisite prospective study over three cycles of chemotherapy. Adult patients from eight European countries about to receive highly and moderately emetogenic chemotherapy were recruited. Clinicians completed a case report form at or before the initial chemotherapy treatment, recording patient demographic and baseline clinical characteristics. Participants completed a daily patient diary for six days per chemotherapy cycle describing their CINV experience. Baseline patient data also included a history of nausea/vomiting (yes/no), patient expectation of nausea (0–100 mm visual analogue scale [VAS]), prechemotherapy anxiety (0–100 mm VAS), and prechemotherapy nausea (0–100 mm VAS) measured during the 24-hour period before chemotherapy initiation.ResultsThere were 991 evaluable patients with complete Cycle 1 data, 888 for Cycle 2 data, and 769 for Cycle 3 data. A complex picture of predictor variables was shown, with different contribution of variables to the acute, delayed, and overall phases of CINV. Key predictor variables included the use of antiemetics inconsistent with international guidelines, younger age, prechemotherapy nausea, and no CINV complete response in an earlier cycle (all at P < 0.05). Anxiety, history of nausea/vomiting, and expectations of nausea were important predictors for some phases and cycles but not consistently across the CINV pathway.ConclusionThe results of this study provide clarity for the relative contribution of a set of characteristics in the development of CINV. Following evidence-based clinical antiemetic guidelines is of paramount importance, alongside treating patients with increased risk for CINV more aggressively, which both could lead to more optimal CINV management. These data can assist clinicians in making decisions about the antiemetic management of their patients.     

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.     

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.     

Randomized double-blind study of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy

Goals Our goal was to evaluate the efficacy and tolerability of the Reliefband as an adjunct to standard antiemetics in patients receiving moderately-high to highly emetogenic chemotherapy.Patients and methods Forty-nine adult cancer patients receiving moderately-high or highly emetogenic chemotherapy were randomized to receive either the active Reliefband (n=26) or an inactive device (n=23). Patients continued to receive all scheduled and as needed antiemetic agents as prescribed. The device was worn the day of chemotherapy administration for 5 days (days 1–5). Patients maintained a daily dairy of nausea severity, vomiting and retching episodes, and antiemetic medications taken. Each patient completed a Functional Living Index Emesis (FLIE) and a tolerability survey at the conclusion of the study. A Wilcoxon rank sum test was used to compare the number of vomiting episodes, severity of nausea and FLIE scores between the two groups.Main results Patients wearing the active Relifband experienced less vomiting (Reliefband 1.9 versus inactive device 4.6 mean episodes; p=0.05), retching (1.4 versus 3.6 mean episodes; p=0.05), and nausea severity (0.91 versus 1.65 mean cm/day; p=0.01) over the 5-day period compared to patients wearing the inactive device. Vomiting was statistically significantly reduced during the delayed period (0.42 versus 1; p=0.032), whereas nausea was significantly reduced during the acute (0.71 versus 2.3; p=0.028) and delayed (1.8 versus 3.3; p=0.020) periods. FLIE scores did not differ between the two treatment groups (91 versus 80; p=0.088).Conclusions This study suggests that patients receiving moderately-high to highly emetogenic chemotherapy who experience nausea and vomiting despite scheduled antiemetics may benefit from the use of the Reliefband as an adjunct to antiemetics. Limitations of this study include differences in risk factors for emesis, chemotherapy, and antiemetic regimens. A larger, better, controlled randomized study is needed to better define optimal use of this device.Supported in part by Woodside Biomedical, Inc., Carlsbad, California USA.     

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.     

A phase II trial of olanzapine,dexamethasone, and palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a Hoosier oncology group study

Objective The purpose of this study is to determine the control of acute and delayed chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately emetogenic chemotherapy (MEC) and highly emetogenic chemotherapy (HEC) with the combined use of palonosetron and olanzapine, and dexamethasone with the dexamethasone given on day 1 only. Materials and methods Forty chemotherapy-naive patients received on the day of chemotherapy, day 1, an anti-emetic regimen consisting of dexamethasone, palonosetron, and olanzapine. Patients continued olanzapine for days 2–4 after chemotherapy administration. Patients recorded daily episodes of emesis, daily symptoms utilizing the M.D. Anderson Symptom Inventory, and the utilization of rescue therapy. Results For the first cycle of chemotherapy, the complete response (no emesis, no rescue) for the acute period (24 h post-chemotherapy) was 100%, the delayed period (days 2–5 post-chemotherapy) 75%, and the overall period (0 120 h post-chemotherapy) 75% in 8 patients receiving HEC and was 97, 75, and 72% in 32 patients receiving MEC. Patients with no nausea for the acute period was 100%, the delayed period 50%, and the overall period 50% in 8 patients receiving HEC and was 100, 78, and 78% in 32 patients receiving MEC. Discussion The complete response and control of nausea in subsequent cycles of chemotherapy were not significantly different from cycle one. Conclusion Olanzapine combined with a single dose of dexamethasone and a single dose of palonosetron was very effective in controlling acute and delayed CINV in patients receiving both HEC and MEC.     

The use of olanzapine versus metoclopramide for the treatment of breakthrough chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy

Purpose

Olanzapine has been shown to be a safe and effective agent for the prevention of chemotherapy-induced nausea and vomiting (CINV). Olanzapine may also be an effective rescue medication for patients who develop breakthrough CINV despite having received guideline-directed CINV prophylaxis.

Methods

A double-blind, randomized phase III trial was performed for the treatment of breakthrough CINV in chemotherapy-naive patients receiving highly emetogenic chemotherapy (cisplatin, ≥?70 mg/m² or doxorubicin, ≥?50 mg/m² and cyclophosphamide, ≥?600 mg/m²), comparing olanzapine to metoclopramide. Patients who developed breakthrough emesis or nausea despite prophylactic dexamethasone (12 mg IV), palonosetron (0.25 mg IV), and fosaprepitant (150 mg IV) pre-chemotherapy and dexamethasone (8 mg p.o. daily, days 2–4) post-chemotherapy were randomized to receive olanzapine, 10 mg orally daily for 3 days or metoclopramide, 10 mg orally TID for 3 days. Patients were monitored for emesis and nausea for 72 h after taking olanzapine or metoclopramide. Two hundred seventy-six patients (median age 62 years, range 38–79; 43 % women; Eastern Cooperative Oncology Group (ECOG) PS 0,1) consented to the protocol. One hundred twelve patients developed breakthrough CINV and 108 were evaluable.

Results

During the 72-h observation period, 39 out of 56 (70 %) patients receiving olanzapine had no emesis compared to 16 out of 52 (31 %) patients with no emesis for patients receiving metoclopramide (p?<?0.01). Patients without nausea (0, scale 0–10, M.D. Anderson Symptom Inventory) during the 72-h observation period were those who took olanzapine, 68 % (38 of 56), and metoclopramide, 23 % (12 of 52) (p?<?0.01). There were no grade 3 or 4 toxicities.

Conclusions

Olanzapine was significantly better than metoclopramide in the control of breakthrough emesis and nausea in patients receiving highly emetogenic chemotherapy.     

A prospective observational study of chemotherapy-related nausea and vomiting in routine practice in a UK cancer centre

Objective The aim of the study was to assess levels of chemotherapy-induced nausea and vomiting (CINV) in routine practice. Materials and methods The study was an observational prospective evaluation using patient self-reports. One hundred and two patients with cancer in a single cancer centre in UK receiving their first chemotherapy treatment participated in the study and were followed up over four cycles, providing a total of 272 assessments of nausea and vomiting. Data was collected with the use of the MASCC Antiemesis Tool (MAT), which is an eight-item short clinical scale assessing acute and delayed nausea and vomiting after chemotherapy. Results Results indicated that acute vomiting was experienced by 15.7% of the patients in cycle 1 and delayed vomiting by 14.7%, while acute nausea was present in 37.3% of the patients and delayed nausea in 47.1%, increasing over the subsequent cycles. Moderately emetogenic and highly emetogenic chemotherapy had the highest incidence of CINV, whereas patients receiving highly emetogenic chemotherapy showed significant levels of delayed nausea. Acute symptoms were more easily controlled than delayed symptoms. Discussion The data suggest that, while vomiting is well controlled, nausea remains a significant problem in practice, and optimal management of CINV is yet to be achieved. Understanding more clearly the biological basis of nausea will assist in managing this complex symptom more effectively in practice.     

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.     

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.     

A phase II trial of olanzapine for the prevention of chemotherapy-induced nausea and vomiting: A Hoosier Oncology Group study

In a previous phase I study, olanzapine was demonstrated to be a safe and effective agent for the prevention of delayed emesis in chemotherapy-naïve cancer patients receiving cyclophosphamide, doxorubicin, and/or cisplatin. Using the maximum tolerated dose of olanzapine in the phase I trial, a phase II trial was performed for the prevention of chemotherapy-induced nausea and vomiting in chemotherapy-naïve patients. The regimen was 5 mg/day of oral olanzapine on the 2 days prior to chemotherapy, 10 mg on the day of chemotherapy, day 1, (added to intravenous granisetron, 10 mcg/kg and dexamethasone 20 mg), and 10 mg/day on days 2–4 after chemotherapy (added to dexamethasone, 8 mg p.o. BID days 2 and 3, and 4 mg p.o. BID day 4). Thirty patients (median age 58.5 years, range 25–84; 23 women; ECOG PS 0, 1) consented to the protocol, and all were evaluable. Complete response (CR) (no emesis, no rescue) was 100% for the acute period (24 h postchemotherapy), 80% for the delayed period (days 2–5 postchemotherapy), and 80% for the overall period (0–120 h postchemotherapy) in ten patients receiving highly emetogenic chemotherapy (cisplatin 70 mg/m²). CR was also 100% for the acute period, 85% for the delayed period, and 85% for the overall period in 20 patients receiving moderately emetogenic chemotherapy (doxorubicin 50 mg/m²). Nausea was very well controlled in the patients receiving highly emetogenic chemotherapy, with no patient having nausea [0 on scale of 0–10, M.D. Anderson Symptom Inventory (MDASI)] in the acute or delayed periods. Nausea was also well controlled in patients receiving moderately emetogenic chemotherapy, with no nausea in 85% of patients in the acute period and 65% in the delayed and overall periods. There were no grade 3 or 4 toxicities and no significant pain, fatigue, disturbed sleep, memory changes, dyspnea, lack of appetite, drowsiness, dry mouth, mood changes, or restlessness experienced by the patients. Complete response and control of nausea in subsequent cycles of chemotherapy (25 patients, cycle 2; 25 patients, cycle 3; 21 patients, cycle 4) were equal to or greater than cycle 1. Olanzapine is safe and highly effective in controlling acute and delayed chemotherapy-induced nausea and vomiting in patients receiving highly and moderately emetogenic chemotherapy.     

Pooled analysis of phase III clinical studies of palonosetron versus ondansetron, dolasetron, and granisetron in the prevention of chemotherapy-induced nausea and vomiting (CINV)

Purpose

Preventing chemotherapy-induced nausea and vomiting (CINV) is integral to treatment success in patients with cancer. This analysis was undertaken to assess the relative efficacy and safety of palonosetron versus older 5HT₃ RAs in preventing CINV associated with moderately or highly emetogenic chemotherapy.

Methods

Patient-level data from four randomized, double-blind, phase III trials comparing palonosetron 0.25 or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg were analyzed. Endpoints included complete response (CR: no emesis and no rescue antiemetics) in the acute (0–24 h), delayed (>24–120 h), and overall (0–120 h) postchemotherapy periods (primary), complete control (CC: no emesis, no rescue antiemetics, and no more than mild nausea), number of emetic episodes, and nausea severity.

Results

CR rates were significantly higher for palonosetron (n?=?1,787) versus older 5HT₃ RAs (n?=?1,175) in the delayed (57 vs 45 %, P?<?0.0001) and overall periods (51 vs 40 %, P?<?0.0001); odds ratios (95 % CI) in the acute, delayed, and overall periods were 1.15 (0.98–1.34), 1.62 (1.40–1.88), and 1.56 (1.34–1.81), respectively. Significant differences in CC rates and nausea severity were observed for the delayed and overall periods and in emetic episodes for all three periods. The incidence of treatment-related adverse events was similar with palonosetron (0.25 mg, 20.0 %; 0.75 mg, 26.5 %) and older 5HT₃ RAs (27.5 %).

Conclusions

Palonosetron is more effective than older 5HT₃ RAs for controlling CINV in the delayed and overall postchemotherapy periods.     

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.     

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.     

Control of emsis by intravenous granisetron in breast cancer patients treated with 5-FU,epirubicin and cyclophosphamide

Granisetron, a potent and selective 5-hydroxytryptamine receptor (5-HT₃) antagonist was reported to be an effective antiemetic agent both in animal studies and in patients given highly emetogenic chemotherapy. A sample of 43 patients with breast cancer was accrued from September to November 1992 in a phase II study to assess the efficacy of granisetron in patients receiving FEC (5-FU, epirubicin, cyclophosphamide). Each patient received 3 mg intravenous granisetron as a single dose just prior to chemotherapy. Oral metoclopromide was prescribed to each patient as a rescue anti-emetic. The emetic episodes and degree of nausea were evaluated on a daily basis. Good control of emesis (0–2 episodes of vomiting) and nausea (mild or no nausea) was in the range 77%–98% and 77%–93% respectively. There was a complete response (no emetic episodes throughout the 6-day period) in 16 patients (37.2%). Onset of emesis tends to occur on day 1 and tend to subside after day 3; 85% of patients had onset of emesis in the first 2 days after chemotherapy. Control of emesis and nausea tends to improve after day 3, which could be the result of the reduced emetogenicity of the combination FEC with time. Altogether, 77% had good control of acute emesis; control of delayed emesis was better with 84% achieving a major response on day 2 after chemotherapy, which improved to more than 90% after day 4. Granisetron was generally tolerated with headache being the most common side-effect folloed by constipation and flushing. This study suggests that granisetron is an effective and well-tolerated anti-emetic agent, which deserves randomised trials to elucidate its efficacy further.     

Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings—a meta-analysis

Purpose

This meta-analysis was performed to evaluate the efficacy of neurokinin-1 receptor antagonists (NK1RAs) for the prevention of chemotherapy-induced nausea and vomiting (CINV) across different categories of chemotherapeutic emetogenicity.

Methods

A systematic review of MEDLINE (via PubMed) and OVID databases, plus major oncology conferences, identified randomized, controlled trials evaluating NK1RAs in combination with a 5-HT₃ RA plus a glucocorticoid for management of CINV. Efficacy end points were no emesis, no nausea, and complete response (CR) rates. Data were analyzed using a random effects model.

Results

Twenty-three trials (N = 11,814) were identified. Based on absolute differences (AD) for no emesis (21 %), no nausea (8 %), CR (16 %), and odd ratios (OR) of 2.62, 1.43, and 2.16, respectively, NK1RA regimens provided better CINV protection versus control groups (all p < 0.00001) in patients receiving cisplatin-based highly emetogenic chemotherapy (HEC). In patients receiving anthracycline/cyclophosphamide (AC)-based HEC, respective ADs and ORs were 14, 4, and 11 % and 1.97 (p < 0.0001), 1.17 (p = 0.04), and 1.62 (p < 0.00001). In patients receiving moderately emetogenic chemotherapy (3 trials), no statistically significant benefit of NK1RAs was found; however, positive trends were detected for CR and no emesis. NK1RAs were effective for CINV prevention in a small number of studies using high-dose chemotherapy as conditioning prior to stem cell transplant and cisplatin-based multiple-day chemotherapy (MDC).

Conclusions

This meta-analysis demonstrated the efficacy of NK1RA in preventing vomiting in patients receiving HEC (including AC), with smaller effects on prevention of nausea. Efficacy is also seen with high-dose chemotherapy and cisplatin-based MDC.

     

The anti-emetic efficacy of tropisetron plus dexamethasone in patients treated with high-dose chemotherapy and stem cell transplantation

Among the most distressing symptoms experienced by patients who have undergone high-dose chemotherapy and stem cell transplantation are nausea and vomiting. The chemotherapy regimens used in high-dose conditioning protocols are highly emetogenic. The 5HT₃ receptor antagonists are very effective in the prevention and abolition of nausea and vomiting resulting from chemotherapeutic drugs. One of them, tropisetron, is a selective antagonist of serotonin 5HT₃ receptors with proven efficacy against emesis. Dexamethasone is also known as an effective agent against nausea and vomiting. The addition of dexamethasone to a 5HT₃ receptor antagonist is synergistic, as has been shown in many trials with highly emetogenic drugs. The aim of the present trial was to study the efficacy and safety profile of the combination of tropisetron and dexamethasone in controlling nausea and vomiting in patients receiving megatherapy prior to stem cell transplantation. We studied 31 patients. All of them were evaluable for response and toxicity. The majority of patients achieved complete or major protection against acute vomiting (71–83%), and 67–84% of the patients had no or mild nausea. The combination was tolerated well, and only a minority of patients reported side effects. Among them the most common were headache (in three patients) and constipation. No patient withdrew from the study because of toxicity. It has become evident from our data that the administration of 5 mg tropisetron daily in combination with 20 mg dexamethasone for 8 days can prevent the acute emesis otherwise experienced by patients receiving high-dose chemotherapy as conditioning in stem cell transplantation programmes.