Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles

We have reported previously that the anti-emetic efficacy of single agent 5HT3 antagonists is not maintained when analysed with the measurement of cumulative probabilities. Presently, the most effective anti-emetic regimen is a combination of a 5HT3 antagonist plus dexamethasone. We, therefore, assessed the sustainment of efficacy of such a combination in 125 patients, scheduled to receive cisplatin > or = 70 mg m(-2) either alone or in combination with other cytotoxic drugs. Anti-emetic therapy was initiated with 10 mg of dexamethasone and 3 mg of granisetron intravenously, before cisplatin. On days 1-6, patients received 8 mg of dexamethasone and 1 mg of granisetron twice daily by oral administration. Protection was assessed during all cycles and calculated based on cumulative probability analyses using the method of Kaplan-Meier and a model for transitional probabilities. Irrespective of the type of analysis used, the anti-emetic efficacy of granisetron/dexamethasone decreased over cycles. The initial complete acute emesis protection rate of 66% decreased to 30% according to the method of Kaplan-Meier and to 39% using the model for transitional probabilities. For delayed emesis, the initial complete protection rate of 52% decreased to 21% (Kaplan-Meier) and to 43% (transitional probabilities). In addition, we observed that protection failure in the delayed emesis period adversely influenced the acute emesis protection in the next cycle. We conclude that the anti-emetic efficacy of a 5HT3 antagonist plus dexamethasone is not maintained over multiple cycles of highly emetogenic chemotherapy, and that the acute emesis protection is adversely influenced by protection failure in the delayed emesis phase.     

Effects of granisetron and its combination with dexamethasone on cisplatin-induced delayed emesis in the ferret

1. Granisetron and its combination with dexamethasone for the treatment of delayed emesis following cisplatin (CDDP) administration were investigated using ferrets. 2. CDDP-induced emesis was significantly inhibited in both the granisetron group and the combined granisetron and dexamethasone group during the acute and delayed phase in terms of total emesis, latency to first emesis and duration of emesis. 3. Food and water consumption in the combined group of ferrets was significantly increased as compared with the CDDP control group. 4. 5-Hydroxytryptamine (5-HT) level was increased in the ileum and the 5-hydroxyindole acetic acid (5-HIAA) level was increased in the area postrema of ferrets after 3 days of CDDP administration. It is suggested that the antiemetic activity of granisetron and/or dexamethasone is not related to 5-HT levels in delayed emesis. 5. Both granisetron and its combination with dexamethasone are effective in CDDP-induced emesis, but combination treatment is more effective than granisetron alone for the duration of emesis in the delayed phase.     

A randomized cross-over study of high-dose metoclopramide plus dexamethasone versus granisetron plus dexamethasone in patients receiving chemotherapy with high-dose cisplatin

We carried out a randomized, single-blind, cross-over trial to compare the antiemetic effect, for both acute and delayed emesis, of granisetron plus dexamethasone (GRN+Dx) with that of high-dose metoclopramide plus dexamethasone (HDMP+Dx). Fifty-four patients with primary or metastatic lung cancer, given single-dose cisplatin (> 80 mg/m2) chemotherapy more than twice, were enrolled in this study. They were treated with both HDMP+Dx and GRN+Dx in two consecutive chemotherapy courses. On day 1, patients experienced a mean of 2.5 (SD = 4.3) and 0.1 (SD = 0.4) episodes of vomiting in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0008). Complete response rate on day 1 was 45 and 90% in the HDMP+Dx and the GRN+Dx groups, respectively (P = 0.0001). Patients treated with GRN+Dx had a tendency to suffer more episodes of vomiting than the HDMP+Dx group on days 2-5, but it was not statistically significant. Twenty-four patients (57%) preferred the GRN+Dx treatment and 14 patients (33%), HDMP+Dx. In the HDMP+Dx group, nine patients (21%) had an extrapyramidal reaction, and 5 patients (12%) had constipation that lasted for at least two days. In contrast, no patients had extrapyramidal reactions, and 18 patients (43%) had constipation in the GRN+Dx group (P < 0.01). GRN+Dx was more effective than HDMP+Dx only in preventing the acute emesis induced by cisplatin. An effective treatment for delayed emesis is still needed.     

Oral ondansetron for the control of cisplatin-induced delayed emesis: a large, multicenter, double-blind, randomized comparative trial of ondansetron versus placebo

PURPOSE: To investigate the efficacy and safety of oral ondansetron in the control of cisplatin-induced delayed emesis in patients who do not require rescue antiemetic therapy for acute emesis. PATIENTS AND METHODS: Five hundred thirty-eight chemotherapy-naive patients who received cisplatin chemotherapy (> or = 70 mg/m2), and who were not rescued for acute emesis, were eligible to be randomized to receive one of the three oral regimens to control delayed emesis. Group I received placebo on days 2 to 6; group II received ondansetron 8 mg twice daily on days 2 and 3 and placebo on days 4 to 6; group III received ondansetron 8 mg twice daily on days 2 to 6. All patients received intravenous ondansetron (0.15 mg/kg every 4 hours for three doses) for the control of acute emesis on day 1. The number of emetic episodes on days 2 and 3 combined (days 2/3, when incidence and severity of delayed emesis were expected to be greatest) was considered the primary measure of efficacy. RESULTS: Patients who received odansetron had significantly fewer emetic episodes on days 2/3, 4, and 5 than those who received placebo (P < or = .002 on each day). Additionally, significantly more patients who received ondansetron had a complete plus major response (C+MR; < or = two two emetic episodes) than those who received placebo on days 2/3 (56% v 37%, P = .001), 4 (94% v 85%, P = .005), and 5 (98% v 88%, P = .006). Patients who received ondansetron had significantly less nausea on day 2/3 when day-1 nausea was used as the baseline score (P = .025). Patients who received ondansetron also had significantly less nausea on day 4 (P = .042) and the results approached significance on day 5 (P = .066). CONCLUSION: Oral ondansetron had a significant effect in the control of cisplatin-induced delayed emesis and nausea in patients who had not required rescue antiemetics during the acute emesis period. The control of delayed nausea and vomiting was most notable in the immediate 2 days following cisplatin administration, with the clinical difference narrowing between the two treatment arms on subsequent days.     

A lymphoma cell line resistant to 4-piperidinopiperidine was less sensitive to CPT-11

The purpose of the study was to assess the toxicity and efficacy of an oral, combination antiemetic regimen including granisetron (Kytril; SmithKline Beecham Pharmaceuticals, Philadelphia, PA, USA) in the setting of highly emetogenic conditioning chemotherapy for stem cell transplantation. Antiemetic prophylaxis consisted of oral granisetron 2 mg once daily, oral prochlorperazine 10 mg q 6 h and oral dexamethasone 4 mg q 6 h, beginning 1 h prior to chemotherapy on each of the 4 days of chemotherapy and continuing until 24 h after the completion of high-dose chemotherapy (HDC). Patients received either CVP (cyclophosphamide 6 g/m2, VP-16 1800 mg/m2 and carboplatin 1200 mg/m2) or CTP (thiotepa 500 mg/m2 in place of VP-16) in four daily doses given over 4 h from days -4 to -1. Previously mobilized and cryopreserved peripheral blood stem cells (PBSC) were reinfused on day +1. Evaluation of nausea, emetic episodes (EE), adverse events, and rescue medications were recorded on a daily patient diary. Thirty-six patients were entered. Fifty-three percent (95% CI = 37-75%) of patients achieved complete response for emesis (CR = 0 EE/24 h) and 75% (95% CI = 58-90%) had combined complete and major response (CR+MR = 0-3 EE/24 h) during all 5 of the treatment days. During the 5 study days, the average number of patient-days with no emesis was 3.7 (74%) and with 1-3 EE was 4.3 (86%). On days -4, -3, -2, -1 and 0, the combined CR+MR rate for emesis was 97, 92, 86, 78 and 75%, respectively. Nausea was absent or mild on all 5 study days in 57% (95% CI = 37-75%). Eight patients had severe late-onset emesis occurring on days +1 to +3 after reinfusion of stem cells. No clinically significant toxicities attributable to the antiemetic regimen were observed. An all oral antiemetic regimen of granisetron, prochlorperazine and dexamethasone appears to be safe and highly effective in patients receiving multiple, daily, high-dose chemotherapy regimens. This regimen offers the advantage of cost-savings, a low side-effect profile and ease of administration in the predominately outpatient setting of HDC with peripheral blood stem cell transplant (PBSCT).     

Antiemetic efficacy of granisetron in pediatric cancer treatment--(2). Comparison of granisetron and granisetron plus methylprednisolone as antiemetic prophylaxis

A crossover clinical trial was carried out to compare the effectiveness and safety of granisetron alone (40 micrograms/kg) with that from a combination of granisetron plus methylprednisolone (MPL, 10 mg/kg) for control of emesis and vomiting induced by anticancer drugs in children with cancer. Complete control of emesis and vomiting were achieved in 95% (19/20 cases) of patients receiving the combination compared to 85% (17/20 cases) of patients receiving granisetron alone. There were no clinical toxicities or side effects in either treatment group. These data indicated that the combination of granisetron plus MPL was superior for control of emesis and vomiting in children receiving cytostatic anticancer drugs.     

Use of oral and intravenous ondansetron in patients treated with cisplatin

Ondansetron, a selective 5-HT3 antagonist, has been shown to be effective in preventing chemotherapy-induced nausea and vomiting. From July and August 1991, 25 patients were accrued in a phase II study to assess the efficacy of ondansetron in patients receiving cisplatin-containing chemotherapy. Patients received intravenous cisplatin 100 mg/m2, given either as a 24-hour infusion on day 1 or in divided doses as eight-hour infusions daily on days 1 to 3. Each patient received 24 mg of ondansetron per day for six days. Intravenous dexamethasone 24 mg was given daily on the days of cisplatin infusion. The emetic episodes and degree of nausea were evaluated daily. "Good" control of emesis (0-2 episodes of vomiting) and nausea (mild or no nausea) ranged from 64-100% and 88-100% respectively. Failure in emesis control occurred most frequently on days 3 and 4. Ondansetron was generally well tolerated with only minimal side-effects. One patient developed unexplained encephalopathy which resolved completely. Our results suggest that ondansetron is an effective anti-emetic agent with minimal toxicities. Randomised studies comparing ondansetron against "standard" anti-emetics should be conducted.     

Familial inv(X) (p22q22): ovarian dysgenesis in two sisters with del Xq and fertility in one male carrier

PURPOSE: To evaluate the antiemetic efficacy and safety of adding the dopamine antagonist prochlorperazine to the combination of granisetron and dexamethasone in the prevention of acute nausea and vomiting following high-dose cisplatin. PATIENTS AND METHODS: Sixty patients receiving cisplatin (> or = 75 mg/m2) (median dose = 100 mg/m2) were enrolled at three sites. Patients received prochlorperazine spansule 15 mg orally, 60 minutes prior to and 12 hours after cisplatin; dexamethasone 20 mg intravenously, 45 minutes prior to cisplatin, and 10 mg intravenously or orally, 12 hours after cisplatin; and granisetron 10 micrograms/kg intravenously, 30 minutes prior to cisplatin. Efficacy was assessed during the 24-hour period after cisplatin using complete antiemetic response (no emetic episodes and no rescue antiemetics) and patient assessment of nausea and satisfaction using 100-mm visual analog scales (nausea: 0 = none, 100 = nausea as bad as it can be; satisfaction: 0 = not at all satisfied, 100 = satisfied as can be). RESULTS: Complete response (0 emetic episodes) was noted in 84% (49/58) of patients. Forty-two patients (72%) experienced no nausea. The mean change in posttreatment nausea visual analog scales from baseline was 8.9 mm. Forty-eight patients (83%) were completely satisfied with their antiemetic treatment. The mean posttreatment patient satisfaction score was 92 mm. Treatment was well tolerated, with infrequent and minor adverse events. CONCLUSIONS: This three-drug antiemetic regimen is well tolerated and highly effective in the prevention of acute nausea and vomiting arising from high-dose cisplatin. Further studies evaluating this regimen are warranted.     

Effect of concurrent use of ondansetron hydrochloride and dexamethasone against nausea and vomiting in lung cancer patients receiving cisplatin

We examined the efficacy of concurrent use of ondansetron hydrochloride and dexamethasone, and the effective dose of dexamethasone against nausea and vomiting in lung cancer patients receiving chemotherapy including single high dose cisplatin. The study was carried out on total of 44 courses of chemotherapy in either initial onset or recurrence of lung cancer. The patients were given 4 mg of ondansetron injection on the day of cisplatin injection (Day 1), and 4 mg/day of ondansetron tablet for Days 2 to 4. These patients were randomly allocated into 2 groups, i.e., those who, on Day 2, concomitantly received 10 mg of dexamethasone (D10 Group, 22 courses) or 20 mg (D20 Group, 22 courses), for comparing the antiemetic effects in a different concomitant dose of dexamethasone. An efficacy rate of 70% or more was achieved in each group for acute emesis on Day 1. The efficacy rate was 80% or above for emesis on Day 2 when dexamethasone was concurrently administered, and Days 3 and 4 in both groups. No significant difference was observed between the groups. A higher complete suppression rate against nausea was seen in D20 Group even though the difference from D10 Group was not significant. Furthermore, food intake rate on Day 2 was significantly better in D20 Group. However, in the cases that were graded effective or markedly effective for acute emesis on Day 1, the efficacy rate was also high in both groups through Days 2-4. It was notable that the efficacy rate of Days 2-4 was 100% in D2 Group. The high efficacy rate was shown in male patients regardless of which dose of dexamethasone was used. However, control of emesis was unfavorable in female patients on Day 1 and was still unfavorable even though dexamethasone was combined from Day 2. We considered from the above results that 10 mg/day of concurrent dexamethasone is sufficient in suppression of delayed emesis on Day 2. However, in order to improve nausea or food intake, or to suppress emesis in patients who are highly likely to show unfavorable control for Day 2 and onward, 20 mg/day should also be effective.     

Combination effect of granisetron plus corticosteroid for prevention of cisplatin-induced emesis: a cross-over study comparing methylprednisolone and dexamethasone

Granisetron (G) is an effective antiemetic drug that is used to prevent cisplatin-induced emesis, although it is less effective for delayed emesis. To enhance the antiemetic effects of granisetron, corticosteroid analogues such as methylprednisolone (M) and dexamethasone (D) were employed in a study of patients treated with cisplatin (CDDP). We investigated the clinical response and urinary excretion of 5-hydroxyindole acetic acid (5-HIAA), the main metabolite of serotonin, in 31 patients with ovarian cancer or uterine endometrial cancer who received CAP therapy (CDDP 75 mg/m2) in a 3-day cross-over trial comparing G + M and G + D treated patients. Both regimens were and delayed emesis than G + D. We conclude that G + D is a more efficacious combination than G + D in protecting patients from CDDP-induced acute and delayed emesis.     

Oral combination antiemetics in patients with small cell lung cancer receiving cisplatin or cyclophosphamide plus doxorubicin

BACKGROUND: Intravenous antiemetic combinations containing a 5-HT3 receptor antagonist (like metoclopramide, ondansetron, or granisetron) with dexamethasone have become the standard therapy for the treatment of acute chemotherapy-induced vomiting. Intravenous antiemetics, however, can be more costly and take more time to prepare and deliver, and therefore are not preferred for home, outpatient, or office use. The objective of this study was to determine the antiemetic activity and safety of the oral combination antiemetic regimen of metoclopramide, dexamethasone, and diphenhydramine in patients with small cell lung cancer receiving standard outpatient chemotherapy programs. METHODS: Fifty-two patients receiving initial cisplatin (60 mg/m2) or cyclophosphamide (600-1500 mg/m2) plus doxorubicin (30-45 mg/m2) received an oral regimen of metoclopramide (3 mg/kg x 2 then 2 mg/kg x 2 or 4 doses), dexamethasone (20 mg) and diphenhydramine (50 mg x 2 or 3 doses) (oral MDD), beginning 30 minutes before chemotherapy. RESULTS: Vomiting was prevented in 15 of 21 (76%) patients (95% confidence interval [CI], 53%-92%) receiving cisplatin and 21 of 31 (71%) individuals (95% CI, 52%-86%) given cyclophosphamide plus doxorubicin. Adverse effects were mild and transient and included sedation, loose stools, akathisia, and hiccoughs. CONCLUSIONS: The oral MDD antiemetic regimen prevented acute emesis in 73% of the patients entered and was well tolerated in this population of patients with small cell lung cancer.     

ABILHAND: a Rasch-built measure of manual ability

BACKGROUND: Dexamethasone decreases chemotherapy-induced emesis when added to an antiemetic regimen. This study was undertaken to evaluate the efficacy of granisetron-dexamethasone combination for the prevention of postoperative nausea and vomiting (PONV) in female patients undergoing general anaesthesia for breast surgery. METHODS: In a randomized, double-blind manner, 135 ASA I patients, aged 40-65 years, were assigned to receive placebo (saline), granisetron 40 micrograms.kg-1 or granisetron 40 micrograms.kg-1 plus dexamethasone 8 mg i.v. (n = 45 of each) immediately before the induction of anaesthesia. A standard general anaesthetic technique and postoperative analgesia were used. The PONV and safety assessments were performed continuously during the first 3 h (0-3 h) and the next 21 h (3-24 h) after anaesthesia. RESULTS: A complete response, defined as no PONV and no administration of rescue antiemetic medication, during 0-3 h after anaesthesia was 51%, 82% and 96% in patients who had received placebo, granisetron and granisetron-dexamethasone combination, respectively; the corresponding incidence during 3-24 h after anaesthesia was 56%, 84% and 98% (P < 0.05; overall Fisher's exact probability test). No clinically important adverse events were observed in any of the groups. CONCLUSION: Prophylactic use of granisetron-dexamethasone combination is more effective than granisetron alone for the prevention of PONV after breast surgery.     

The effects of dexamethasone on antiemetics in female patients undergoing gynecologic surgery

This randomized, double-blind study compared the effects of dexamethasone plus either droperidol, metoclopramide, or granisetron with each antiemetic alone for preventing postoperative nausea and vomiting (PONV) in 270 female patients undergoing general anesthesia for major gynecological surgery. Patients were randomly assigned to receive either droperidol 1.25 mg (Group D1, n = 45), droperidol 1.25 mg plus dexamethasone 8 mg (Group D2, n = 45), metoclopramide 10 mg (Group M1, n = 45), metoclopramide 10 mg plus dexamethasone 8 mg (Group M2, n = 45), granisetron 40 micrograms/kg (Group G1, n = 45), or granisetron 40 micrograms/kg plus dexamethasone 8 mg (Group G2, n = 45) immediately before the induction of anesthesia. A standard general anesthetic technique and postoperative analgesia were used throughout the study. Complete response, defined as no PONV and no administration of rescue antiemetic medication during the first 24 h after anesthesia, was 49% in Group D1, 60% in Group D2 (P = 0.199 versus Group D1), 51% in Group M1, 62% in Group M2 (P = 0.198 versus Group M1), 80% in Group G1, and 96% in Group G2 (P = 0.025 versus Group G1). Our results suggest that dexamethasone enhances the antiemetic efficacy of granisetron but does not potentiate the other antiemetics-droperidol and metoclopramide-in female patients undergoing major gynecological surgery. Implications: We compared the efficacy of dexamethasone plus three different antiemetics-droperidol, metoclopramide, and granisetron-for the prevention of nausea and vomiting after gynecologic surgery. The granisetron-dexamethasone combination was the most effective for preventing post-operative emetic symptoms.     

Efficacy of granisetron in the prevention of emesis induced by conditioning chemotherapy for allogeneic bone marrow transplantation

We conducted this study to compare granisetron, 5-HT3 antagonist, with conventional antiemetics in the prophylaxis of emesis induced by conditioning chemotherapy for allogeneic bone marrow transplantation in 41 patients. The conditioning chemotherapy regimen included either cytosine arabinoside 2 g/m2 x 4 and cyclophosphamide 60 mg/kg x 2 (CA, CY), or busulfan 4 mg/kg x 4 and cyclophosphamide 60 mg/kg x 2 (BU, CY). In CA and CY regimen, the clinical effective rate with granisetron against emesis was 94.1% on the 1st day, compared with 7.6% in the control group. On day 2 and 3, the effective rate with granisetron was 58.8% and 23.5%, respectively, compared with 0% in the control group. In the BU and CY regimen, control of emesis with granisetron on day 5 and 6 was 66.7%, against 20.0% in the control group. Based on these data, we concluded granisetron is superior to conventional antiemetics in the prophylaxis of emesis induced by conditioning for allogeneic bone marrow transplantation.     

Control of emesis 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 followed 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.     

Efficacy of granisetron as anti-emetic agent for emesis induced by intra-arterial injection therapy for hepatocellular carcinoma

The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.     

Review of the preclinical pharmacology and comparative efficacy of 5-hydroxytryptamine-3 receptor antagonists for chemotherapy-induced emesis

PURPOSE: This analysis was undertaken to review published reports of the comparative efficacy and safety of 5-hydroxytryptamine-3 (5-HT3) receptor antagonists in the prophylaxis of acute chemotherapy-induced emesis. METHODS: Comparison data used are the preclinical pharmacology as well as the design and results of clinical trials. Seven comparative studies that used granisetron, ondansetron, or tropisetron in patients who received either moderately or highly emetogenic chemotherapy are reviewed. As the study designs, patient population, chemotherapy, antiemetic doses and schedule, and methods of assessment were slightly different, the results of each study are analyzed independently. Effectiveness is assessed by emetic episodes, nausea, and patient preference. RESULTS: The preclinical pharmacologic profile is different among the 5-HT3 antagonists in terms of potency, selectivity, dose response, and duration of action. The comparative clinical trials show that a single intravenous (i.v.) dose of granisetron 3 mg is as effective as multiple (8 mg x 3) or single (32 mg) i.v. doses of ondansetron for the prevention of acute nausea and emesis due to cisplatin. In the two moderately emetogenic clinical trials, granisetron 3 mg i.v. was at least as effective as ondansetron 8 mg i.v. +/- 24 mg orally and tropisetron 5 mg i.v. Patient preference was evaluated in three of the four crossover trials: granisetron was preferred in three of four, and no preference was reported in the fourth. The one trial to compare ondansetron 0.15 mg/kg x 3 versus granisetron 10 micrograms/kg x 1 or granisetron 40 micrograms/kg i.v. demonstrated equivalent control of nausea and vomiting in patients who received cisplatin-based chemotherapy. CONCLUSION: The 5-HT3 receptor antagonists compared are highly effective antiemetic agents that have now become the standard of care for preventing chemotherapy-induced emesis. Whether the described preclinical differences among these agents are also clinically significant remains to be seen. In the comparative trials analyzed, the 5-HT3 receptor antagonists demonstrated relatively equivalent clinical efficacy. Cost analysis may favor the use of one agent over another depending on the emetogenic challenge, dose of the 5-HT3 antagonists, and number of doses recommended. Patient preference may be an important factor to be considered in future antiemetic trials.     

Treatment of cisplatin-related nausea and vomiting with a combination of ondansetron and metoclopramide: a pilot study

Forty chemotherapy-naive patients receiving high-dose cisplatin were included in a pilot study of a combination of ondansetron plus metoclopramide as antiemetic therapy. Patients received ondansetron 16 mg plus metoclopramide 0.5 mg/kg in 250 cm3 of normal saline i.v. 15 min before cisplatin administration on day 1; then ondansetron 8 mg was given orally b.i.d. and metoclopramide 0.5 mg/kg was given intramuscularly t.i.d. for 4 days. This combination was given to all patients receiving the first cycle of chemotherapy. At the second cycle of chemotherapy all patients received the same antiemetic treatment as above plus methylprednisolone 125 mg i.v. on day 1 and the intramuscularly once a day for 4 days. There were 20 females and 20 males with a mean performance status of 1 (range 0-2) and a mean age of 58 years (range 36-68). Ten patients had ovarian carcinoma, eight patients had uterine adenocarcinoma and 22 and non-small cell lung carcinoma. The mean cisplatin dose was 96 mg/m2. All patients denied significant alcohol consumption. At cycle 1, complete protection against acute emesis was achieved in 22 patients (55%), major protection in 12 cases (30%), minor protection in four patients (10%) and failure in two cases (5%). On the other hand, the efficacy of this combination on delayed vomiting was not striking. For delayed vomiting, complete protection was observed in nine patients (23%), major protection in 13 cases (33%), minor protection in 10 patients (25%) and failure in eight cases (20%). At cycle 2, patients also received methylprednisolone showing complete protection from vomiting in 19 cases (47%) and major protection on 12 cases (30%). Results achieved with ondansetron plus metoclopramide are in the range reported for ondansetron alone in the medical literature. Although this study was not prospectively carried out in a randomized fashion, the results are not suggestive of a possible positive effect of metoclopramide addition to ondansetron. On the other hand, these results stress the role that corticosteroids may play in the control of delayed emesis. Toxicity was predictable and the frequency of side-effects was in the range reported in other studies with ondansetron.     

Computer simulation of changes in nursing productivity from early tracheal extubation of coronary artery bypass graft patients

A total of 530 patients were treated in this multicenter, double-blind, double-dummy, parallel group study to compare the anti-emetic efficacy and safety of a once daily ondansetron oral regimen with a once daily i.v. dosing regimen over a 24 h period, administered to patients prior to receiving cisplatin (50 mg/m2 or greater) chemotherapy. Patients were randomized to receive a single dose of ondansetron plus dexamethasone given either orally (ondansetron 24 mg and dexamethasone 12 mg, n=262) or i.v. (ondansetron 8 mg and dexamethasone 20 mg, n=268). Complete control of emesis (i.e. no emetic episodes, no rescue and no premature withdrawal) was achieved for 85% of patients (224 of 262) in the oral group and 83% (223 of 268) in the i.v. group. No nausea was reported in 70% of patients in the oral group and 68% in the i.v. group. There were no statistically significant differences between the two groups for any of the assessments of efficacy, which included time to first emetic episode, number of emetic episodes and the worst grade of nausea occurring over the 24 h study period. Once daily ondansetron oral and i.v., in combination with dexamethasone, was well tolerated in this study. In conclusion, once daily oral ondansetron 24 mg plus dexamethasone is equally effective in the control of emesis and nausea induced by highly emetogenic chemotherapy as once daily ondansetron 8 mg i.v. plus dexamethasone.     

The effect of continuous light on refractive error and the ocular components of the rat

The anti-emetic efficiency of orally administered ondansetron and granisetron has been tested in macaques exposed to a mixed y and neutron radiation (6 Gy) with a high neutron/gamma-ray ratio. Our experiments reveal that a single delivery of ondansetron (1 or 2 mg kg(-1)) or of granisetron (0.25 mg kg(-1)) 45-90 min before irradiation or 35-45 min after irradiation was not totally effective. Conversely, the delivery of two doses with the same delay prior to and after exposure led to a complete prevention of vomiting and retching. These observations can be explained by the dual mechanism of radiation-induced emesis: an early peripheral mechanism and a later central mechanism. Two deliveries of 5-HT3 receptor antagonists seem to disrupt serotonergic transmission at the brain stem structures and to affect the peripheral release of serotonin from the gut, thus completely preventing radiation-induced vomiting. This study confirms that the 5-HT3-dependent mechanisms that mediate emesis are similar for both neutron and gamma radiation.