Granisetron compared with prednisolone plus metopimazine as anti-emetic prophylaxis during multiple cycles of moderately emetogenic chemotherapy

Abstract

Summary This randomized, double-blind, double-dummy parallel study compared the anti-emetic efficacy and tolerability of the serotonin antagonist granisetron with prednisolone plus the dopamine D 2 antagonist metopimazine during nine cycles of moderately emetogenic chemotherapy. Chemotherapy naive women with stage I or II breast cancer scheduled to intravenous cyclophosphamide, fluorouracil and methotrexate or cyclophosphamide, epirubicin and fluorouracil every 3 weeks were included. Patients received a single intravenous dose of granisetron 3 mg or a 3-day oral treatment with prednisolone 25 mg once a day plus metopimazine 30 mg four times a day. A total of 223 women were enrolled and 218 patients (97.8%) were evaluable for efficacy. Granisetron (n = 109) was superior to prednisolone plus metopimazine (n = 109) in the prophylaxis of acute nausea and vomiting during the first cycle of chemotherapy (P < 0.001) and prednisolone plus metopimazine was superior on days 2-5 (P = 0.002). Overall, granisetron was superior on days 1-5 (P = 0.009). The median number of cycles completed with granisetron was five (95% confidence interval 4-6) compared with two (95% confidence interval 2-2) for prednisolone plus metopimazine (P = 0.0019). Constipation and rash were reported more frequently with granisetron (P < 0.001 and P = 0.043 respectively) and palpitations more frequently with prednisolone plus metopimazine (P = 0.015). In conclusion, the number of cycles completed with granisetron was significantly higher than the number completed with prednisolone plus metopimazine, but the anti-emetic efficacy of both treatments declined during multiple cycles of moderately emetogenic chemotherapy.

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

“…After 4 cycles, the cumulative emetic control was 0.51 with the combination and 0.25 with tropisetron alone. This study clearly demonstrates, as shown in previous trials with non-cisplatin-based chemotherapy [16,17] that differences in the efficacy of different antiemetic treatments might only appear if patients are followed-up during multiple cycles of chemotherapy.…”

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

“…After 4 cycles, the cumulative emetic control was 0.51 with the combination and 0.25 with tropisetron alone. This study clearly demonstrates, as shown in previous trials with non-cisplatin-based chemotherapy [16,17] that differences in the efficacy of different antiemetic treatments might only appear if patients are followed-up during multiple cycles of chemotherapy.…”

Acute emesis: moderately emetogenic chemotherapy

“…As described in the previous guidelines [2, 12], dexamethasone has been consistently equal or superior to metoclopramide and equal to 5-HT 3 -receptor antagonists such as ondansetron [21] and granisetron [19] in patients receiving cyclophosphamide-or anthracycline-based chemotherapy. Two randomized studies have indicated that dexamethasone plus prochlorperazine [31] or prednisolone plus metopimazine [28] is inferior to granisetron in patients receiving MEC. In the first study chemotherapy also included cisplatin (20-50 mg/m 2 ) and in the second study prednisolone was given in a dose equal to only 50% of the recently established optimal dose of dexamethasone [20].…”

“…In the first study 223 patients were followed through nine cycles of CMF/CEF chemotherapy (total number of cycles 898). Neither granisetron alone nor prednisolone plus metopimazine was able to maintain antiemetic efficacy [28]. These antiemetic regimens are, however, no longer recommended as a standard for prophylaxis of emesis induced by MEC.…”

Comparative activity of antiemetic drugs

“…The percentage of patients experiencing no acute emesis with metopimazine plus ondansetron was 63-78% compared with 47-50% for ondansetron monotherapy [80][81][82]. Metopimazine combined with prednisolone was significantly less effective than granisetron in the acute setting [83].…”

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

“…After 4 cycles, the cumulative emetic control was 0.51 with the combination and 0.25 with tropisetron alone. This study clearly demonstrates, as shown in previous trials with non-cisplatin-based chemotherapy [16,17] that differences in the efficacy of different antiemetic treatments might only appear if patients are followed-up during multiple cycles of chemotherapy.…”

Acute emesis: moderately emetogenic chemotherapy

“…As described in the previous guidelines [2, 12], dexamethasone has been consistently equal or superior to metoclopramide and equal to 5-HT 3 -receptor antagonists such as ondansetron [21] and granisetron [19] in patients receiving cyclophosphamide-or anthracycline-based chemotherapy. Two randomized studies have indicated that dexamethasone plus prochlorperazine [31] or prednisolone plus metopimazine [28] is inferior to granisetron in patients receiving MEC. In the first study chemotherapy also included cisplatin (20-50 mg/m 2 ) and in the second study prednisolone was given in a dose equal to only 50% of the recently established optimal dose of dexamethasone [20].…”

“…In the first study 223 patients were followed through nine cycles of CMF/CEF chemotherapy (total number of cycles 898). Neither granisetron alone nor prednisolone plus metopimazine was able to maintain antiemetic efficacy [28]. These antiemetic regimens are, however, no longer recommended as a standard for prophylaxis of emesis induced by MEC.…”

Comparative activity of antiemetic drugs

“…The percentage of patients experiencing no acute emesis with metopimazine plus ondansetron was 63-78% compared with 47-50% for ondansetron monotherapy [80][81][82]. Metopimazine combined with prednisolone was significantly less effective than granisetron in the acute setting [83].…”

Randomized, double-blind trial comparing the antiemetic effect of tropisetron plus metopimazine with tropisetron plus placebo in patients receiving multiple cycles of multiple-day cisplatin-based chemotherapy

“…After 4 cycles, the cumulative emetic control was 0.51 with the combination and 0.25 with tropisetron alone. This study clearly demonstrates, as shown in previous trials with non-cisplatin-based chemotherapy [16,17] that differences in the efficacy of different antiemetic treatments might only appear if patients are followed-up during multiple cycles of chemotherapy.…”

Acute emesis: moderately emetogenic chemotherapy

“…As described in the previous guidelines [2, 12], dexamethasone has been consistently equal or superior to metoclopramide and equal to 5-HT 3 -receptor antagonists such as ondansetron [21] and granisetron [19] in patients receiving cyclophosphamide-or anthracycline-based chemotherapy. Two randomized studies have indicated that dexamethasone plus prochlorperazine [31] or prednisolone plus metopimazine [28] is inferior to granisetron in patients receiving MEC. In the first study chemotherapy also included cisplatin (20-50 mg/m 2 ) and in the second study prednisolone was given in a dose equal to only 50% of the recently established optimal dose of dexamethasone [20].…”

“…In the first study 223 patients were followed through nine cycles of CMF/CEF chemotherapy (total number of cycles 898). Neither granisetron alone nor prednisolone plus metopimazine was able to maintain antiemetic efficacy [28]. These antiemetic regimens are, however, no longer recommended as a standard for prophylaxis of emesis induced by MEC.…”

Comparative activity of antiemetic drugs

“…The percentage of patients experiencing no acute emesis with metopimazine plus ondansetron was 63-78% compared with 47-50% for ondansetron monotherapy [80][81][82]. Metopimazine combined with prednisolone was significantly less effective than granisetron in the acute setting [83].…”