Medline ® Abstracts for References 11,69-73
of 'Prevention and treatment of chemotherapy-induced nausea and vomiting in adults'
Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin-induced emesis. The Granisetron Study Group.
Heron JF, Goedhals L, Jordaan JP, Cunningham J, Cedar E
Ann Oncol. 1994;5(7):579.
PATIENTS AND METHODS: Three anti-emetic treatment regimens were compared in 357 patients receiving cisplatin therapy (mean dose 81 mg/m2) in this double-blind randomized study. Regimens studied were i) granisetron 1 mg bd orally for 7 days (granisetron alone); ii) gran 1 mg bd orally for 7 days plus prophylactic dexamethasone (12 mg i.v.) on the first day only (gran/dex); iii) metoclopramide (3 mg/kg i.v. loading dose; 4 mg/kg i.v. infusion) plus dex (12 mg i.v.) on the first day followed by met 10 mg orally tds for a further 6 days (met/dex).
RESULTS: At 24 hours, gran/dex was significantly superior to met/dex in terms of total anti-emetic control, defined as no nausea, no vomiting, no rescue anti-emetic therapy, not withdrawn (54.7% gran/dex vs. 37.2% met/dex; P<0.01). There was also a significant delay in time to onset of nausea (P<0.01) and vomiting (P<0.01) following gran/dex compared with met/dex. Oral granisetron alone was as effective as met/dex in control of acute emesis in all parameters examined. There were no significant differences between the three groups in the control of delayed nausea and vomiting. The most common adverse experiences in both granisetron groups were headache and constipation, both characteristic of 5-HT3 antagonists. Agitation, somnolence, diarrhoea and decreased appetite were reported more frequently by the met/dex group.
CONCLUSIONS: Oral granisetron as a single agent is as effective as high doses of i.v. met/dex in preventing cisplatin-induced emesis. Oral granisetron in combination with a corticosteroid provides superior anti-emetic control to the met/dex regimen in patients undergoing highly emetogenic chemotherapy.
Centre François Baclesse, Caen, France.
Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer.
Italian Group for Antiemetic Research
N Engl J Med. 1995;332(1):1.
BACKGROUND: Serotonin-receptor antagonists seem to be as effective as corticosteroids in preventing emesis induced by moderately emetogenic antineoplastic agents. We compared the antiemetic effect of a combination of granisetron and dexamethasone with that of granisetron or dexamethasone administered alone.
METHODS: From December 1992 to January 1994, 482 consecutive patients who were to receive moderately emetogenic chemotherapy for the first time (600 to 1000 mg of cyclophosphamide per square meter of body-surface area,>or = 50 mg of doxorubicin per square meter,>or = 75 mg of epirubicin per square meter, or>or = 300 mg of carboplatin per square meter, alone or in some combination) were enrolled in a double-blind, randomized, multi-center study evaluating the efficacy and toxicity of three antiemetic regimens. The following antiemetic regimens were used: 8 mg of dexamethasone given intravenously before chemotherapy plus 4 mg given orally immediately before chemotherapy and then every six hours for a total of four doses, 3 mg of granisetron given intravenously before chemotherapy, or a combination of granisetron and dexamethasone given in the doses used for the single-drug regimens.
RESULTS: We evaluated 408 patients (136 receiving dexamethasone, 137 receiving granisetron, and 135 receiving both drugs). In the first 24 hours after chemotherapy, complete protection from vomiting and complete protection from nausea were achieved in 70.6 and 55.1 percent, respectively, of the patients receiving dexamethasone, in 72.3 and 48.2 percent of those receiving granisetron, and in 92.6 and 71.9 percent of those receiving granisetron combined with dexamethasone (P<0.001 for all comparisons). Patients who received granisetron alone had less protection from delayed vomiting and nausea than those who received dexamethasone alone or the two drugs combined. All the regimens were equally well tolerated.
CONCLUSION: Granisetron combined with dexamethasone was the most effective regimen for the prevention of emesis induced by moderately emetogenic chemotherapy.
Medical Oncology Division, Policlinico Hospital, Perugia, Italy.
Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone.
Roila F, Tonato M, Cognetti F, Cortesi E, Favalli G, Marangolo M, Amadori D, Bella MA, Gramazio V, Donati D
J Clin Oncol. 1991;9(4):675.
Ondansetron (OND) is a new 5-HT3 receptor antagonist that give complete protection from emesis/nausea in approximately 50% of cisplatin (CDDP)-treated patients. To evaluate if dexamethasone (DEX) added to OND increases antiemetic efficacy, we carried out a double-blind randomized crossover study to compare the antiemetic activity of OND with OND plus DEX. One hundred two chemotherapy-naive patients (44 women and 58 men) scheduled to receive CDDP chemotherapy at doses greater than or equal to 50 mg/m2 entered the study. Eighty-nine patients completed both cycles with the following results: complete protection from emesis/nausea was obtained in 57/59 patients (64.0%/66.3%) with OND and in 81/79 (91.0%/88.8%) with OND plus DEX (P = .0005/P = .0021). At the end of the study, 53% of the patients expressed a treatment preference, and of these, 74% chose OND plus DEX compared with 26% who preferred OND alone, a statistically significant difference (P less than .003). Side effects were very mild and not significantly different between the two treatments. We conclude that OND plus DEX is more efficacious than OND in protecting patients from CDDP-induced emesis and nausea.
Division of Medical Oncology, Regional Hospital, Perugia, Italy.
Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron?
Smyth JF, Coleman RE, Nicolson M, Gallmeier WM, Leonard RC, Cornbleet MA, Allan SG, Upadhyaya BK, Bruntsch U
OBJECTIVE: To determine the contribution of dexamethasone to the efficacy of the 5-hydroxytryptamine antagonist ondansetron in control of cisplatin induced nausea and vomiting.
DESIGN: Randomised double blind crossover study.
SETTING: Two cancer centres in teaching hospitals, one in the United Kingdom and the other in Germany.
SUBJECTS: 100 patients (53 men and 47 women) new to cisplatin chemotherapy, 84 of whom completed two consecutive courses of chemotherapy.
INTERVENTIONS: Patients were given intravenous dexamethasone (20 mg) or physiological saline with intravenous ondansetron 8 mg before cisplatin, then ondansetron 1 mg/h for 24 hours. Oral ondansetron 8 mg was taken three times daily on days 2-6.
MAIN OUTCOME MEASURES: Incidence of complete or major control of emesis (0-2 episodes in the 24 hours after chemotherapy).
RESULTS: Complete or major control was obtained in 49 out of 71 (69%) of patients after receiving ondansetron plus dexamethasone compared with 40 out of 71 (56%) when they were given ondansetron alone (p = 0.012). This effect was most pronounced in the first 12 hours after chemotherapy. Patients receiving the combination also had significantly less nausea. Of the 53 patients who expressed a preference, 38 (72%) preferred the combination treatment (p = 0.002) to ondansetron alone. The effect of ondansetron on delayed emesis was less pronounced.
CONCLUSIONS: Dexamethasone makes a significant contribution to the efficacy of ondansetron in the control of acute platinum induced emesis.
Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Edinburgh.
A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis.
Hesketh PJ, Harvey WH, Harker WG, Beck TM, Ryan T, Bricker LJ, Kish JA, Murphy WK, Hainsworth JD, Haley B
J Clin Oncol. 1994;12(3):596.
PURPOSE: This study compares the efficacy and safety of ondansetron alone with that of ondansetron plus dexamethasone in the prevention of emesis induced by high-dose cisplatin (>or = 100 mg/m2).
PATIENTS AND METHODS: This multicenter study used a randomized, double-blind, parallel-group design. Chemotherapy-naive patients were randomized to receive intravenous (IV) ondansetron (Zofran, Cerenex Pharmaceuticals, Research Triangle Park, NC) 0.15 mg/kg for three doses every 4 hours beginning 30 minutes before cisplatin administration either alone or in combination with dexamethasone 20 mg administered 45 minutes before cisplatin. Cisplatin (>or = 100 mg/m2) was administered as a single infusion (<or = 3 hours). Patients were monitored for emetic episodes (EEs), adverse events, and laboratory safety parameters for 24 hours after cisplatin administration.
RESULTS: A total of 275 patients were enrolled. Of these, 245 were assessable for efficacy. Patients who received ondansetron plus dexamethasone had a higher complete antiemetic response rate (61% v 46%, P = .02) and less nausea (posttreatment visual analog scale mean 18.2 v 32.8, P<.001) than did those who received ondansetron alone. The time to the first EE was longer for patients in the group that received ondansetron plus dexamethasone (P = .005). Headache (12%), diarrhea (2%), and abdominal colic (1%) were the most common antiemetic-related adverse events reported. The incidence of adverse events was similar between the treatment groups.
CONCLUSION: IV ondansetron in combination with dexamethasone is safe and more effective than ondansetron alone in the prevention of emesis induced by high-dose cisplatin.
Boston University Medical Center, MA.
Ondansetron plus dexamethasone is superior to ondansetron alone in the prevention of emesis in chemotherapy-naive and previously treated patients. Swiss Group for Clinical Cancer Research (SAKK).
Joss RA, Bacchi M, Buser K, Kirchner V, Neuenschwander H, Orth B, Aapro MS, Thürlimann B
Ann Oncol. 1994;5(3):253.
BACKGROUND: This prospective, randomized, double-blind study assessed whether the addition of dexamethasone to ondansetron leads to improved control of chemotherapy--induced emesis, both in patients undergoing their first course of highly emetogenic chemotherapy and in chemotherapy-pretreated patients refractory to standard anti-emetics.
PATIENTS AND METHODS: Patients were randomized to receive either 20 mg dexamethasone as an intravenous infusion or placebo plus ondansetron 8 mg 15 minutes prior to and 4 and 8 hours after the administration of chemotherapy. According to the randomisation code patients received from day 2 to day 5 either ondansetron 8 mg p.o. + placebo p.o., three times daily, or ondansetron 8 mg p.o. + dexamethasone 4 mg p.o., three times daily. Patients undergoing multiple-day treatment received intravenous study treatment on the days of chemotherapy and thereafter oral treatment as outlined above.
RESULTS: A total of 215 patients were entered into the study. Of these, 207 were evaluable (111 previously-untreated and 96 previously-treated patients). In the chemotherapy-naive patients the combination of ondansetron plus dexamethasone was significantly superior to ondansetron plus placebo in protecting the patients completely from emesis (retching and vomiting) (81% versus 64%, p = 0.04). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated patients than in those receiving ondansetron plus placebo (0.8 versus 2.1, p = 0.03). In this group of patients there was significantly superior protection from emesis on the second day (p-value = 0.04), and a trend towards a better protection on the third and fourth days. On each day the active combination offered better protection from nausea with an approximately 20% difference in favor of ondansetron plus dexamethasone. In the group of established vomiters the combination of ondansetron plus dexamethansone was superior to ondansetron plus placebo in protecting the patients from acute emesis, with 70% versus 48% of the patients being completely protected (p = 0.03). The mean number of vomiting episodes was significantly lower in the ondansetron-plus-dexamethasone-treated-patients than in those receiving ondansetron plus placebo (0.9 versus 2.1, p = 0.02). In the ondansetron-plus-dexamethasone arm 55% of the patients had complete protection from nausea, retching and vomiting compared to 35% in the ondansetron-plus-placebo-treated group (p = 0.05). Overall 22% of the patients (20% in the ondansetron-plus-placebo and 25% in the ondansetron-plus-dexamethasone arm) experienced at least one, usually mild, adverse event. More patients in the ondansetron-plus-dexamethasone arm complained of epigastric pain or burning (8/101 versus 4/112, p-value = 0.16). The difference in patients reporting constipation (6/101 versus 0/112) was highly significant at a p-value of 0.008.
CONCLUSIONS: The combination of dexamethasone plus ondansetron is more effective in protecting chemotherapy-naive patients undergoing their first course of highly emetogenic chemotherapy with cisplatin and chemotherapy-pretreated patients refractory to standard antiemetics from chemotherapy-induced nausea and vomiting compared to ondansetron plus placebo.
Department of Medicine, Kantonsspital, Luzern, Switzerland.