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.     

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.     

A phase II study of ondansetron as antiemetic prophylaxis in patients receiving high-dose polychemotherapy and stem cell transplantation

The field of high-dose chemotherapy with stem cell transplantation has been expanded recently as a treatment for solid tumors and hematological malignancies. Severe emesis remains one of the main extramedullary side-effects of high-dose regimens during the first week of treatment. Traditional antiemetics such as chlorpromazine, diazepam, and phenothiazines are extensively used but are unable to control emesis. The new antiemetic ondansetron, a serotonin receptor (5HT₃) antagonist appears to be superior to these drugs for cisplatin-induced emesis. The study we present here is an attempt to control emesis following high-dose regimens, during bone marrow or peripheral stem cell transplantation, with ondansetron. To our knowledge no other paper has reported the efficacy of this antiemetic in such group of patients. A total of 29 patients who received highly emetogenic polychemotherapy as conditioning regimens for bone marrow transplantation were treated with ondansetron, which was given as an 8-mg i.v. short infusion prior the initiation of treatment and every 6 h thereafter for 3 days, and an 8-mg dose every 8 h for 5 additional days. All the patients had previously been treated with chemotherapy and were evaluable for response and toxicity. Complete and major protection of vomiting on day 1 was achieved by 76% of the patients, 58% on day 2 and 52% on day 3. Nausea was absent or mild in 79% of patients on day 1, 45% on day 2 and 41% on day 3. For the days 4–8 as a whole, complete and major protection against vomiting was achieved by 59%–86% of the patients, while 51%–90% of patients had no or mild nausea. The most frequent side-effects were headache (24%) and constipation (17%). On the basis of these results we conclude that ondasetron can be succesfully used as an effective antiemetic prophylaxis for patients who receive megatherapy and bone marrow rescue, and should allow the majority of these patients to receive their treatment without serious side-effects and discomfort.     

Granisetron in the control of nausea and vomiting associated with bone marrow transplantation: a review of its efficacy and tolerability

Cancer patients undergoing bone marrow transplantation (BMT) experience severe nausea and vomiting associated with high-dose chemotherapy agents; these emetic symptoms are compounded by total body irradiation used in many conditioning regimens. This paper reviews clinical experience with the 5-HT₃ receptor antagonist granisetron, both as a single agent and in combination with other anti-emetics, in patients undergoing BMT and peripheral blood stem cell transplantation (PBSCT). Clinical studies demonstrate the efficacy (47–61% with no vomiting and no worse than mild nausea) and tolerability of granisetron. Its long half-life and duration of action may be responsible for its effective 24 h control of nausea and vomiting in BMT patients.     

Oral dolasetron mesilate (MDL 73,147EF) for the control of emesis during fractionated total-body irradiation and high-dose cyclophosphamide in patients undergoing allogeneic bone marrow transplantation

 The purpose of the present study was to evaluate the efficacy and safety of oral dolasetron mesilate in the prevention of nausea and vomiting that might otherwise be induced by total-body irradiation (TBI) and high-dose cyclophosphamide. In an open non-comparative study 20 patients who received TBI for 3 days and high-dose cyclophosphamide chemotherapy for 2 days as part of their preparation for bone marrow transplantation were given oral dolasetron mesilate at dosages ranging from 50 to 200 mg 1 h before each fraction of radiotherapy and cyclophosphamide administration. Initial rescue therapy consisted of intravenous dolasetron mesilate. If nausea and vomiting remained uncontrolled, standard antiemetics were to be used. Of the 20 patients, 13 had only two emetic episodes or fewer in the 3-day TBI period. On days 1 and 2 of cyclophosphamide administration, 11 and 6 patients had fewer than two emetic episodes. From day 1 to day 3, 15 patients experienced no nausea or only mild nausea, and on the days of chemotherapy 8 and 7 patients had mild nausea or none at all. Rescue with i.v. dolasetron mesilate was needed by 3 and 6 patients during the TBI and the chemotherapy periods respectively. In 2 patients additional antiemetics were used on days 2–3 and 4–5. Mild to moderate headache was reported in 6 patients. No unexpected abnormalities were observed in haematology, biochemistry or urinalysis, and vital signs were unaffected throughout the study period. The data suggest that oral dolasetron mesilate is effective and safe for the prevention of nausea and vomiting during TBI and cyclophosphamide chemotherapy prior to bone marrow transplantation. Future controlled studies should evaluate combination antiemetic therapy with dolasetron mesilate for this indication.     

Antiemetics in cancer chemotherapy: historical perspective and current state of the art

Chemotherapy-related nausea and vomiting can today be controlled with available antiemetics in a high percentage of patients but emesis remains a problem for some patients, with certain drugs and with repeated cycles of chemotherapy. The fundamental steps of clinical research in antiemetics towards the improvement of the control of nausea and vomiting with new drugs or combinations are presented. Special emphasis is given to cisplatin-induced nausea and vomiting because of the frequency and relevance of this phenomenon. The use of high-dose metoclopramide, its combination with steroids, and later the addition of lorazepam or diphenhydramine represented the evolving standard of the 1980s, with the level of complete protection from vomiting improving from 30%–40% to 60%–70% with the three-drug combination. The introduction of new agents such as the 5-hydroxytryptamine 3 (5-HT3) receptor antagonists has recently offered new possibilities because of their activity and lack of toxicity. In particular, the combination of ondansetron plus dexamethasone is today the most efficacious and least toxic antiemetic treatment for prevention of emesis in patients treated with a single high dose or low repeated doses of cisplatin. A comparison of different 5-HT3 antagonists, always in combination with steroids, is now considered necessary. For patients treated with moderately emetogenic chemotherapy the use of steroids can still be considered the standard treatment. In this setting, the role of 5-HT3 receptor antagonists, alone or in combination with steroids, has to be better defined through large, well-planned clinical trials, which should have a cost-effectiveness analysis as one of their goals.     

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.     

Ondansetron is effective in decreasing postoperative nausea and vomiting.

The efficacy of ondansetron, a selective 5-HT3 receptor antagonist, in preventing postoperative nausea and vomiting in surgical patients was studied. Fifty women were randomized in a double-blind manner to receive either two 8 mg doses of intravenous ondansetron or two doses of placebo vehicle: the first given just before general anesthesia induction and the second 8 hours later. During the first 24 postoperative hours, the number of emetic episodes was recorded and the subjects rated their nausea on a scale from 0 to 10. Ondansetron-treated subjects had fewer emetic episodes (p less than 0.001) and lower subjective nausea scores (p less than 0.001). The number of complete responders (no emetic episodes and no rescue therapy) was 1 of 24 (4%) and 15 of 26 (58%) in the placebo and ondansetron groups, respectively (p less than 0.001). Ondansetron is clearly more effective than placebo in the prophylaxis of postoperative nausea and vomiting. The adverse event profile for ondansetron was similar to that of placebo.     

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.     

Using aprepitant as secondary antiemetic prophylaxis for cancer patients with cisplatin-induced emesis

Purpose

Chemotherapy-induced emesis remains a problem despite prophylaxis with 5-hydroxytryptamine (5-HT3) antagonists and dexamethasone. The purpose of the current study was to evaluate the efficacy of adding aprepitant, a neurokinin-1(NK-1) receptor antagonist, as a secondary antiemetic prophylaxis in cases failing to achieve full protection against emesis during the first cycle of a cisplatin-based regimen.

Methods

Patients receiving chemotherapy with a dose of at least 50?mg/m² of cisplatin-based regimens were eligible. If patients failed to achieve complete protection against vomiting when antiemetics (5-HT3 antagonists and dexamethasone) were given in cycle 1, aprepitant was added in subsequent cycles. The primary endpoint was complete response (no emetic episodes and no rescue antiemetics) during days 1–6.

Results

We analyzed 257 patients consecutively. Forty-nine patients (19%) had acute and/or delayed emesis during the first cycle of chemotherapy. Forty of 49 patients received aprepitant for secondary prophylaxis of emesis in the second cycle. Complete protection from vomiting and nausea was achieved in 63% and 55% of patients, respectively. Thirty-five patients received aprepitant for the third cycle. Complete protection from vomiting and nausea was achieved in 77% and 71% of patients, respectively.

Conclusions

Primary antiemetic prophylaxis with 5-HT3 antagonists plus dexamethasone provided more than 80% complete protection against cisplatin-induced emesis. Addition of aprepitant as secondary antiemetic prophylaxis in subsequent cycles provided adequate emesis protection in patients who failed primary prophylaxis. Using aprepitant as secondary antiemetic prophylaxis for cancer patients with cisplatin-induced emesis is feasible and cost-effective.     

Aprepitant for the control of delayed nausea and vomiting associated with the use of high-dose melphalan for autologous peripheral blood stem cell transplants in patients with multiple myeloma: a phase II study

Study objective

The aim of this study is to evaluate the efficacy of aprepitant as part of the antiemetic regimen for high-dose melphalan conditioning in multiple myeloma patients.

Design

This is a prospective, single-arm study.

Setting

The study was conducted at an Academic Medical Facility.

Subjects

Twenty-six patients receiving high-dose melphalan with autologous stem cell support were included in this study.

Intervention

Eligible patients were >18 years with a diagnosis of MM undergoing high-dose melphalan followed by autologous peripheral blood stem cell transplantation (PBSCT). All patients had serum aminotransferases and total bilirubin less than 2× upper limit of normal. Treatment consisted of aprepitant 125 mg orally on day 1, followed by 80 mg orally 24 and 48 h after the initial dose; ondansetron 16 mg orally day 1; dexamethasone 12 mg orally day 1, and 8 mg orally days 2–4 with breakthrough medications as needed.

Measurements and main results

Patients were evaluated for the frequency of emetic episodes, the need for breakthrough antiemetic medication, and the mean nausea score in 24-h increments beginning 24 h after chemotherapy and continuing until 120 h. Nausea score was determined using a linear analog scale (0–10). Complete response (CR) was defined as no more than one (1) emetic episode during the evaluation period. A total of 26 patients (17 male, 9 female) were enrolled in the study. Of these, 25 (96 %) were complete responders and 24 (92 %) had no documented emetic episodes during the study period. One patient (4 %) had 1 emetic episode and one patient (4 %) had 2 emetic episodes. Some degree of nausea was reported by 23/26 patients, and the mean nausea score for the entire group over the study period was 0.7 (range 0–10).

Conclusions

Addition of aprepitant to standard antiemetics resulted in low rates of delayed nausea/vomiting associated with high-dose melphalan and PBSCT, and has now become standard practice in this patient population at our institution.     

Probable involvement of the 5-hydroxytryptamine(4) receptor in methotrexate-induced delayed emesis in dogs

Delayed emesis in cancer patients undergoing chemotherapy remains a significant problem. The pathogenesis of delayed emesis is still obscure. It was recently demonstrated that methotrexate (MTX), an anticancer drug, evoked delayed emesis in dogs in a manner similar to its actions in humans. We evaluated the antiemetic activity of FK1052, a potent antagonist for both the 5-hydroxytryptamine (HT)(3) and 5-HT(4) receptors, on delayed emesis induced by MTX in beagle dogs. Animal behavior was recorded for 3 days using a video camera. Delayed emesis lasting up to 72 h was observed in dogs treated with MTX (2.5 mg/kg i.v.), but acute emesis did not occur. The following antiemetics, at the dose that prevents cisplatin-induced acute emesis in dogs, were administered i.v. as multiple injections every 12 h during days 2 to 3. FK1052 (1 and 3.2 mg/kg) significantly reduced the emetic episodes caused by MTX, whereas ondansetron (1 mg/kg), a selective 5-HT(3) receptor antagonist, was not effective. The emetic episodes induced by MTX were also inhibited by another 5-HT(3/4) receptor antagonist, tropisetron (1 mg/kg). CP-122,721 (0. 1 mg/kg), a potent selective tachykinin NK(1) receptor antagonist, significantly reduced the emetic responses to MTX. Copper sulfate-induced emesis in dogs was also prevented by FK1052, tropisetron, and CP-122,721 but not by ondansetron. FK1052, tropisetron, and ondansetron had negligible affinity for the NK(1) receptor at 1 microM. These results suggest that the 5-HT(4) receptor may be in part involved in the production of delayed emesis induced by MTX in dogs and that FK1052 may be a useful drug against both acute and delayed emesis induced by cancer 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.     

Progress in reducing anticipatory nausea and vomiting: a study of community practice

 Chemotherapy-related nausea and vomiting (NV) in 300 consecutive patients treated in community practices prior to the availability of 5-HT₃ antiemetics (9/87 to 1/91) were compared with NV in a second sample of 300 patients treated after their commercial introduction (9/93 to 2/95). Eighty-six percent of the later patients received 5-HT₃ antiemetics, and significantly fewer (43.3%) reported one or more episodes of posttreatment vomiting during their first four cycles of chemotherapy compared with those in the previous sample (55.0%: P < .01). Identical numbers of both groups (79.3%) reported at least one episode of posttreatment nausea. A significant increase in the average duration of both posttreatment nausea (from 28.1 h to 37.2 h;P = 0.001) and posttreatment vomiting (from 10.9 h–16.5 h, P = .02) was found; no significant differences were seen in the reported severity of either symptom. The proportion of patients experiencing at least one episode of anticipatory nausea (31.0% vs 32.0%) or anticipatory vomiting (7.7% vs 6.3%) did not differ significantly (P > 0.5) between groups, nor were there significant differences in the duration or severity of anticipatory symptoms (P > 0.4 for all comparisons). The reduction in the frequency of posttreatment vomiting supports research findings of efficacy. Findings of an increase in duration of posttreatment nausea and emesis and no change in the frequency of posttreatment nausea or in anticipatory symptoms show a continuing need for progress in control of posttreatment emesis and emphasize the need for further research on the control of chemotherapy-induced nausea.     

Electroacupuncture for refractory acute emesis caused by chemotherapy

PURPOSE: To evaluate the efficacy of electroacupuncture in preventing anthracycline-based chemotherapy-related nausea and emesis refractory to combination 5HT(3)-antagonist and dexamethasone. PATIENTS AND METHODS: Cancer patients with refractory emesis after their first cycle of doxorubicin-based chemotherapy were accrued into this study. Electroacupuncture was given during the second cycle of chemotherapy. Each patient was evaluated for the number of emetic episodes and grade of nausea within the first 24 hours after chemotherapy and electroacupuncture. RESULTS: Forty-seven of a total of 317 patients screened were eligible for this study. Of these, 27 patients agreed to participate. Twenty-six (26; 96.3%) of them had significant reduction in both nausea grade and episodes of vomiting after electroacupuncture. There was complete response with no emetic episodes in 37%. Subjectively, 25 (92.6%) of the total 27 patients believed that acupuncture was an acceptable procedure and was helpful in reducing emesis. Electroacupuncture was well-tolerated with a median pain score of 3 of 10. CONCLUSION: Electroacupuncture is well-tolerated and effective as an adjunct in reducing chemotherapy-related nausea and emesis.     

Evaluation of outcomes in converting from intravenous ondansetron to oral granisetron: an observational study

OBJECTIVE: To describe a systematic evaluation of the outcomes associated with revising institutional guidelines for the prevention of acute chemotherapy-induced nausea and vomiting (CINV) to promote cost-effective use of the serotonin (5-HT3) antagonists. METHODS: The 5-HT3 antagonist of choice in the antiemetic guidelines was revised from intravenous ondansetron to oral granisetron in August 1995. Patient assessments were conducted immediately prior to (Period 1) and after (Period 2) guideline revision using validated questionnaires. The effectiveness of the two 5-HT3 antagonists were compared and reported to the prescribing oncologists. Outcomes were assessed one year after guideline revision (Period 3) using identical methods. RESULTS: No difference was found in the rate of total control (no emesis, no nausea) between patients receiving oral granisetron (60%) and intravenous ondansetron (56%) (p = 0.408, Period 1 vs. 2). Nausea severity, the number of emesis episodes, and use of rescue antiemetics were also equivalent. Prescriber compliance with using the 5-HT3 antagonist of choice and dose increased from 48% to 61% following adoption of oral granisetron. By Period 3, compliance increased to 78%, and satisfactory control of acute CINV was again documented. The costs for prevention of acute CINV decreased from $107 in Period 1 (intravenous ondansetron only) to $65 in Period 3 (oral granisetron). CONCLUSIONS: Outcomes associated with use of oral granisetron and intravenous ondansetron were equivalent in this patient population. Guideline revision and outcome documentation by the oncology pharmacists resulted in increased compliance with institution guidelines and a 40% cost savings.     

Patient-controlled antiemesis for cancer chemotherapy-induced nausea and vomiting

Nausea and emesis during cancer chemotherapy are very common, but can often be controlled with repetitive boli of antiemetic drugs. However, some patients, especially those with anticipatory symptoms, experience nausea and emesis despite antiemetic prophylaxis. An increased participation of these patients in the prophylaxis and treatment of these highly subjective symptoms may lead to better palliation. A patient controlled infusion pump was assessed in nine patients receiving cisplatin, in whom high-dose metoclopramide (5 mg/kg) had failed (>3 emetic episodes) during previous treatment cycles. Improved palliation was achieved in every case with on-demand boli in combination with a continuous infusion of metoclopramide or droperidol. Eight of the nine patients preferred the patient-controlled system to the conventional fixed-dose bolus regimens. The infusion pump functioned safely and reliably. Antiemetic treatment with the patient-controlled device was superior to previous conventional methods in this group of diffcult-to-treat patients.     

Oral cisapride for the control of delayed vomiting following high-dose cisplatin

Although combination antiemetics prevent vomiting during the initial 24 h after high-dose (≥100 mg/m²) cisplatin, many patients experience delayed emesis 24–120 h afterwards despite receiving prophylactic dexamethasone and metoclopramide during this time. Cisapride is a prokinetic agent, which stimulates propulsive motility throughout the gastrointestinal tract without causing extrapyramidal effects. In this phase II trial, we tested the ability of cisapride to prevent delayed emesis following cisplatin. Twenty patients receiving initial cisplatin ≥100 mg/m² were entered. All patients received intravenous dexamethasone with either metoclopramide or ondansetron to prevent acute emesis 0–24 h after receiving cisplatin. Patients who had experienced two or fewer acute vomiting episodes then received cisapride 20 mg orally four times daily for 4 days (24–120 h after cisplatin). Cisapride prevented delayed emesis in 2 patients (10%) during the entire 4-day period (95% confidence interval, 1–32%). Abdominal cramping and pain occurred in 35%. At the dose and schedule tested, oral cisapride prevented delayed emesis in only 10% of patients receiving cisplatin ≥100 mg/m² and caused abdominal cramping in 35%. Since in prior trials among similar patients, placebo prevented delayed emesis in 11%, further study of cisapride and dose escalation for this indication are not recommended.     

A double-blind,placebo-controlled trial of i.v. dolasetron mesilate in the prevention of radiotherapy-induced nausea and vomiting in cancer patients

The aim of this work was to measure the safety and efficacy of single i.v. doses of dolasetron mesilate for the control of emesis caused by single high-dose (at least 6 Gy) radiotherapy to the upper abdomen. The double-blind, placebo-controlled, multicenter study stratified patients on the basis of being naive or nonnaive to radiotherapy. Patients with or without a history of previous chemotherapy were enrolled. Patients were randomized to receive placebo or 0.3, 0.6, or 1.2 mg/kg dolasetron mesilate 30 min before radiotherapy, then monitored for 24 h. Antiemetic efficacy was assessed from the time to the first emetic episode or rescue, from whether there was a complete response (0 emetic episodes/no rescue medication) or a complete-plus-major response (0-2 emetic episodes/no rescue medication), from the severity of nausea (rated by patients and the investigator), and from the investigator's assessment of efficacy. Fifty patients completed the study (owing to changing medical practice, enrollment objectives were not met; consequently, no significant linear dose trend was expected). Pooled dolasetron was superior to the placebo in its effect on the time to first emesis or rescue in radiotherapy-nonnaive patients (P=0.015). Dolasetron was statistically superior to the placebo in the overall population on the basis of a complete plus major response:54%, 100%, 93%, and 83% for the placebo and 0.3-, 0.6-, and 1.2-mg/kg doses respectively (P=0.002). The low response in the highest dose group may be due to an imbalance in the number of chemotherapynonnaive patients in that group. Dolasetron was superior to the placebo on the basis of nausea assessed by the investigator (P=0.024) and administration of rescue medication (P=0.006). Complete response at the 0.3-mg/ kg dose was superior to results with the placebo (P=0.050). Treatment-related adverse events were rare, mild to moderate in intensity, and evenly distributed across the four groups. Overall, dolasetron mesilate was effective and well-tolerated in the control of single, high-dose radiotherapy-induced emesis.     

Comparison of an orally disintegrating ondansetron tablet with the conventional ondansetron tablet for cyclophosphamide-induced emesis in cancer patients: a multicenter, double-masked study. Ondansetron Orally Disintegrating Tablet Emesis Study Group.

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% (defined 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.