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.     

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.     

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.     

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.     

Clinical evaluation of 2 mg granisetron tablet for nausea and vomiting induced by anticancer drugs including cisplatin

1. The clinical efficacy and safety of the 2 mg granisetron tablet were assessed in 32 mainly lung cancer patients who were to receive treatment with anticancer drugs including CDDP. 2. One 2 mg granisetron tablet was administered prophylactically one hour before the start of CDDP administration. 3. Based on the development of nausea and vomiting in 24 hours after the start of CDDP administration, the study medication was judged to be "remarkably effective" or "effective" in 71.0% (22/31) of cases. 4. The study medication was judged to be "safe" in 96.9% (31/32) of cases, without causing any adverse reactions. 5. The above results indicate that the 2 mg granisetron tablet is safe and useful.     

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.     

Reduction of cisplatin-induced emesis by a selective neurokinin-1-receptor antagonist. L-754,030 Antiemetic Trials Group

BACKGROUND: The localization of substance P in brain-stem regions associated with vomiting, and the results of studies in ferrets, led us to postulate that a neurokinin-1-receptor antagonist would be an antiemetic in patients receiving anticancer chemotherapy. METHODS: In a multicenter, double-blind, placebo-controlled trial involving 159 patients who had not previously received cisplatin, we evaluated the prevention of acute emesis (occurring within 24 hours) and delayed emesis (on days 2 to 5) after a single dose of cisplatin therapy (70 mg or more per square meter of body-surface area). Before receiving cisplatin, all the patients received granisetron (10 microg per kilogram of body weight intravenously) and dexamethasone (20 mg orally). The patients were randomly assigned to one of three treatments in addition to granisetron and dexamethasone: 400 mg of an oral trisubstituted morpholine acetal (also known as L-754,030) before cisplatin and 300 mg on days 2 to 5 (group 1), 400 mg of L-754,030 before cisplatin and placebo on days 2 to 5 (group 2), or placebo before cisplatin and placebo on days 2 to 5 (group 3). Additional medication was available at any time to treat occurrences of vomiting or nausea. RESULTS: In the acute-emesis phase, 93 percent of the patients in groups 1 and 2 combined and 67 percent of those in group 3 had no vomiting (P<0.001). In the delayed-emesis phase, 82 percent of the patients in group 1, 78 percent of those in group 2, and 33 percent of those in group 3 had no vomiting (P<0.001 for the comparison between group 1 or 2 and group 3). The median nausea score in the delayed-emesis phase was significantly lower in group 1 than in group 3 (P=0.003). No serious adverse events were attributed to L-754,030. CONCLUSIONS: The neurokinin-1-receptor antagonist L-754,030 prevents delayed emesis after treatment with cisplatin. Moreover, combining L-754,030 with granisetron plus dexamethasone improves the prevention of acute emesis.     

Modern aspects of antiemetic therapy

We summarized the current knowledge about chemotherapy and radiotherapy-induced nausea and vomiting. Nausea and vomiting are among the most frequent side effects in the treatment of malignancies, and they are very unpleasant for the patient. We reviewed basic aetiological and physiological mechanisms (except that of delayed emesis, which is not enough explored), particularly the role of serotonin in acute chemotherapy and radiotherapy-induced nausea and vomiting. An oncologist cannot make many changes in the treatment of malignancies and patient-related prognostic factors, but he (she) can make changes in the treatment of nausea and vomiting in order to improve the quality of life of patients with malignancies. We also listed some of the most widely used antiemetic drugs with their most important pharmacological properties. Important progress in the control of nausea and vomiting was obtained by the use of selective antagonists of 5-HT3-receptors such as ondansetron, granisetron, tropisetron and dolasetron. Usually ondasetron and granisetron were used. Their clinical activity is similar but better results were obtained with the combination of 5-HT3-antagonists and corticosteroids (complete response was approximately 90%) than by their individual use (complete response was approximately 50%). The problem of delayed emesis has not yet been solved, and best results were obtained with the combination of metoclopramide and corticosteroids. For the control of nausea and vomiting caused by radiotherapy, orally given ondansetron is effective.     

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.     

Generating a normalized geometric liver model using warping

This review discusses the development and use of 5-hydroxytryptamine3 (5-HT3) antagonists, especially granisetron, for the treatment of chemotherapy-induced emesis. Following recent evidence suggesting that high-dose chemotherapy is more effective in increasing tumor response rate and median survival time, more effective antiemetic control is essential. Granisetron, a new 5-HT3, is approximately 400 times more potent than metoclopramide and, unlike metoclopramide, does not produce extrapyramidal side effects. Granisetron has been shown to be effective as a single prophylactic dose, over 5 days and in patients receiving repeated cycles of chemotherapy. Patients with nausea and vomiting within the first 24 h after chemotherapy are more likely to experience delayed symptoms; however, episodes of breakthrough nausea and vomiting can be controlled by intervention with one, and in some cases more, doses of granisetron. The development of granisetron represents an important advance in the control of chemotherapy induced 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.     

A randomized trial of tropisetron in the prophylaxis of nausea and vomiting induced by chemotherapy

Thirty patients receiving cisplation or non-cisplatin (containing cyclophosphamide and adriamycin) chemotherapy were enrolled in a randomized, crossover study comparing the efficacy of single dose of Navoban (tropisetron, 5 mg) and Kytril (granisetron, 3 mg). The effective control of acute vomiting induced by cisplatin was achieved in 95.2% (20/21) of patients receiving Navoban and 90.5% (19/21) in those receiving Kytril. Complele control rate was 71.4% (15/21) in Navoban arm, and 81.0% (17/21) in Kytril arm. Total control of delayed vomiting (day 2-5) was 71.4%-90.4% in Navoban arm, while it was 66.7%-4% in Kytril arm. The effective control of vomiting induced by non-cisplatin drugs was achieved in 9/9 in both arms. It is concluded that both agents are effective in the control of vomiting induced by chemotherapy. They have identical adverse effects and are well tolerated by the patients.     

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.     

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.     

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.     

Prophylactic oral antiemetics for preventing postoperative nausea and vomiting: granisetron versus domperidone

In this prospective, randomized, double-blinded study, we evaluated the efficacy of the oral antiemetics, granisetron and domperidone, for the prevention of postoperative nausea and vomiting (PONV) in 100 women undergoing major gynecologic surgery. Patients received either granisetron 2 mg or domperidone 20 mg (n = 50 in each group) orally 1 h before surgery. Standardized anesthetic techniques and postoperative analgesia regimens were used. Complete response (defined as no PONV and no administration of rescue antiemetic medication) for 0-3 h after anesthesia was 88% with granisetron and 52% with domperidone; the corresponding incidence for 3-24 h after anesthesia was 86% and 48% (P < 0.05). No clinically important adverse events due to the drugs were observed in any of the groups. In conclusion, the efficacy of preoperative oral granisetron is superior to that of domperidone for the prevention of PONV after major gynecologic surgery. IMPLICATIONS: We compared the efficacy of granisetron and domperidone administered orally for the prevention of postoperative nausea and vomiting in women undergoing gynecologic surgery. Preoperative oral granisetron was more effective than domperidone.     

Patients' self-reported functional status after granisetron or ondansetron therapy to prevent chemotherapy-induced nausea and vomiting at six cancer centers

Patient functional status after administration of either granisetron or ondansetron to prevent acute chemotherapy-induced nausea and vomiting (CINV) was studied. Pharmacists and nurses from six cancer centers distributed Functional Living Index-Emesis (FLIE) questionnaires to 115 outpatients receiving either granisetron or ondansetron for prevention of CINV. The emetogenic potential of each patient's chemotherapy regimen was high, moderately high, or moderate. Immediately before and 72 hours after chemotherapy, each patient rated his or her reaction to each of 18 items on the questionnaire on a 7-point scale. Possible scores ranged from 18 to 126, with higher scores indicating higher levels of functioning. The occurrence of nausea in the granisetron group was 40.0% compared with 43.2% in the ondansetron group; the occurrence of vomiting was 18.8% in the granisetron group and 11.1% in the ondansetron group. Patients who received highly emetogenic chemotherapy had significantly lower scores on the FLIE after chemotherapy than before. Patients with both nausea and vomiting reported a much higher negative impact on functional status after chemotherapy than those with nausea only. The mean prechemotherapy and postchemotherapy FLIE scores were 124.2 and 110.4 for granisetron and 124.9 and 111.9 for ondansetron. Granisetron and ondansetron did not differ significantly in their effect on functional status reported by patients before and 72 hours after receiving cancer 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.     

Efficacy and safety of two methods of administration of granisetron injection for nausea and vomiting induced by chemotherapy for tumors in hematopoietic organs--a randomized crossover comparison between intravenous drip infusion and intravenous bolus injection]

We investigated the efficacy and safety of two methods of granisetron injection to treat nausea and vomiting induced by chemotherapy for tumors in hematopoietic organs. The methods of administration were intravenous drip infusion over 30 minutes, which is the conventional method, and intravenous bolus injection. In this study, 89.5% of patients in both groups (17/19 for each) were free from vomiting. No serious adverse events were observed in either administration group. Abnormal laboratory test values suspected to be related to granisetron were observed in 3 cases in the bolus injection group and in 2 cases in the drip infusion group. but did not pose any clinical problem. These results demonstrated the safety of both methods of administration. In conclusion, it is considered that granisetron intravenous bolus injection can be considered as the method of choice for the prevention of nausea and vomiting induced by chemotherapy for tumors in hematopoietic organs.