Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis

Abstract

Summary Two hundred and seventy-eight adult chemonaive patients receiving moderately emetogenic chemotherapy were randomly allocated to receive either intravenous (i.v.) granisetron 3 mg plus i.v. dexamethasone 8 mg or i.v. granisetron 3 mg plus i.v. placebo dexamethasone prior to chemotherapy. Eighty-two per cent of all patients recruited were female, and 91% of all patients consumed less than 10 units of alcohol per week, suggesting a study population with an increased risk of nausea and vomiting. In the first 24 h 85% of patients who received granisetron plus dexamethasone were complete responders compared with 75.9% of the patients receiving granisetron alone (P = 0.053). There were statistically significant improvements in complete response over 7 days (P = 0.029) and in the numbers of patients receiving rescue antiemetic (P = 0.0004). Toxicity was minimal with no significant differences between treatment groups. These results confirm the antiemetic activity of granisetron and show that it has an additive effect in combination with dexamethasone.As single agents the 5HT3 antagonists granisetron (Marty, 1992;Chevallier, 1993) ondansetron (De Mulder, 1990) and tropisetron (De Bruijn, 1992) have been shown to be at least as effective as conventional treatments in controlling the acute nausea and vomiting experienced by patients receiving highly emetogenic chemotherapeutic regimens. Furthermore, they have an improved safety profile. There is now evidence indicating that the addition of a corticosteroid to ondansetron further enhances its efficacy in the acute phase (Roila, 1991;Smyth, 1991), although to date there are no similar data for granisetron.The management of delayed emesis, however, remains less than satisfactory with existing therapies, with around 50% of patients remaining uncontrolled (Kris, 1989). The combination of metoclopramide and dexamethasone has been shown to be better than either dexamethasone or placebo (Kris, 1989;Moreno, 1992). However, the place of 5HT3 antagonists in the management of delayed emesis is as yet unclear. Indeed, oral ondansetron alone has not been demonstrated to be superior to either dexamethasone (Jones, 1991) or metoclopramide (De Mulder, 1990). The objective of this study was therefore to compare the safety and efficacy of intravenous granisetron plus dexamethasone phosphate with that of intravenous granisetron alone in the prevention of both acute and delayed emesis induced by moderately emetogenic cytotoxic chemotherapy. Patients and methods Study designThe study was a double-blind, randomised, parallel group study carried out at 18 centres in the UK. Patients gave their witnessed written or verbal informed consent to participate in the study and were informed that they were free to withdraw at any time. The Cytotoxic chemotherapy regimens Patients received at least one of the following cytotoxic drugs: carboplatin > 300 mg m2, cisplatin 20-50 mg dacarbazine 350-500 mg m-2, cyclophosphamide > 500 mg m 2 (in combination), doxorubicin>40 mg m2 (single agent), doxoru...

Role of dexamethasone dosage in combination with 5-HT3 antagonists for prophylaxis of acute chemotherapy-induced nausea and vomiting

“…Trials using either dose have been published (Campora et al, 1994;Carmichael et al, 1994). The benefit of additional corticosteroid therapy to 5-HT 3 antagonists is undisputed.…”

“…Earlier studies have mainly investigated different corticosteroid quantities in comparison with no or placebo medication. Prior work in this area suggests that especially patients with low prechemotherapy night-time cortisol excretion profit from cortisol administration (Fredrickson et al, 1992), that endogenous cortisol exerts antiemetic effects similar to that of exogenous corticosteroids (Hursti et al, 1993), and dexamethasone in high doses (20 mg) may impair the control of delayed symptoms (Peterson et al, 1996) whereas this adverse effect was not observed at doses of 8 mg (Carmichael et al, 1994).…”

Antiemetic therapy options for chemotherapy-induced nausea and vomiting in breast cancer patients

“…For acute CINV, complete response rates can be achieved among 60%-70% and 80%-90% of patients who undergo high emetogenic and moderately emetogenic chemotherapy, respectively. [16][17][18][19] However, 5-HT3 receptor antagonists are not universally accepted as standard prophylactic therapy for delayed CINV. 1,14 In a meta-analysis by Geling et al, 5-HT3 receptor antagonists (excluding palonosetron) did not significantly improve control of delayed CINV.…”

Palonosetron and dexamethasone for prevention of nausea and vomiting in patients receiving high-dose chemotherapy with auto-SCT

“…3 In addition, uncontrolled CINV can lead to severe clinical conditions, such as electrolyte imbalance, dehydration and malnutrition, and thus uncontrolled CINV not only compromises quality of life, but also influences the patient's ability to respond to treatment. 4 In the 1990s, the introduction of serotonin receptor antagonists (5-HT 3 RAs) improved the management of acute CINV associated with both moderately and highly emetogenic CT, [5][6][7][8] but no improvement was shown in the prophylaxis of delayed CINV. [9][10][11][12] The second-generation 5-HT 3 RA, namely palonosetron, and the neurokinin receptor antagonist, aprepitant, have improved not only the prevention of acute CINV, but also the prophylaxis of delayed CINV [13][14][15][16][17][18][19] after both moderately and highly emetogenic CT.…”