Efficacy and tolerability of tropisetron in comparison with a combination of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin-containing chemotherapy

Sorbe, Bengt; Högberg, Thomas; Himmelmann, Anna; Schmidt, M.; Räisänen, I.; Stockmeyer, M; Bruijn, K M de

doi:10.1016/0959-8049(94)90534-7

Cited by 29 publications

(17 citation statements)

References 12 publications

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“…The combination was significantly superior to tropisetron monotherapy in controlling both acute emesis (89% vs 75%) and delayed emesis (81% vs 59%). Sorbe et al [26] demonstrated in 63 patients that cisplatin-treated patients not entirely protected by tropisetron monotherapy experienced a significant increase in efficacy under the tropisetron-dexamethasone combination in the next cycle. More than 50% of the patients treated in this manner remained asymptomatic throughout the entire cycle.…”

Section: Discussionmentioning

confidence: 98%

“…Even with this highly effective therapy, however, a not inconsiderable proportion of patients continue to suffer from nausea and emesis -not only on the day of chemotherapy administration but also on subsequent days. As regards the acute treatment of emesis, a substantial number of randomized studies have demonstrated that efficacy can be increased very effectively by combining 5HT 3 antagonists with corticosteroids [10,14,26]. Hardly any data have so far been submitted on combinations with other classes of compounds, such as dopamine antagonists, and the available studies have concentrated mainly on acute emesis.…”

Section: Introductionmentioning

confidence: 97%

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Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

Drechsler

Bruntsch

Eggert

et al. 1997

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There is still controversy as to what constitutes the optimal therapy for acute and delayed chemotherapy-induced emesis and nausea. We conducted a threearmed randomized multi-centre study in 193 chemotherapy-naive patients receiving highly emetogenic chemotherapy inducing both acute and delayed symptoms (cisplatin 650 mg/m 2 , carboplatin 6300 mg/m 2 , cyclophosphamide 6750 mg/m 2 , ifosfamide 61.5 g/m 2 on day 1). Group A: 1!5 mg tropisetron i.v. on day 1c2, then 10 mg p.o. (oral dose now recommended: 5 mg); group B: tropisetron as for Acdexamethasone, 20 mg i.v., on days 1c2, then 4 mg i.v./p.o.; group C: tropisetron as for Acmetoclopramide, 20 mg i.v.c2!10 mg p.o. on day 1, then 3!10 mg p.o. Treatment was continued for at least 2 days after the end of chemotherapy. Tropisetroncdexamethasone was significantly superior to tropisetron alone both for acute (Pp0.0064) and delayed (Pp0.0053) emesis. Complete control of acute and delayed emesis (nausea) was achieved in 80% (75%) and 53% (46%) in group A, 97% (90%) and 80% (58%) in group B, and 86% (80%) and 49% (45%) in group C. Patients completely asymptomatic during the whole cycle accounted for 26% of those in group A, 49% in group B and 28% in group C. The most frequent adverse events were constipation (16.6%), headache (7.3%) and tiredness (7.3%). Once-daily tropisetroncdexamethasone over several days is well tolerated and is a simple means of achieving further significant improvement in the efficacy of tropisetron against acute and delayed symptoms.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 97%

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

Drechsler

Bruntsch

Eggert

et al. 1997

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“…One possible cause of this anomaly is the species differences between humans and shrews. Clinically, DEX and a 5-HT 3 antagonist together have demonstrated the ability to block the vast majority of acute vomiting due to CIS (Drechsler et al, 1997; Sorbe et al, 1994), but were ineffective even in combination when administered to the house musk shrew ( Suncus murinus ; Sam et al, 2003). In contrast to Suncus , however, to date the data related to emesis in the least shrew have been very similar to those collected for people (Darmani, 1998; Darmani et al, 2008; Darmani et al, 1999; Ray et al, 2008; and unpublished observations), and our previously published single-dose data regarding DEX administered alone have indeed shown reduced emetic activity (Darmani et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

The antiemetic interaction of Δ9-tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew

Wang

Ray

McClanahan

et al. 2009

Pharmacology Biochemistry and Behavior

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5-HT 3 receptor antagonists (e.g. tropisetron) combined with dexamethasone are effective for the acute phase of cisplatin (CIS)-induced emesis. This study determined the possible additive or synergistic antiemetic efficacy of Δ 9 -THC when combined with tropisetron or dexamethasone (DEX). Δ 9 -THC (0 -10 mg/kg i.p.) was injected in combination with tropisetron (0 -5 mg/kg i.p.) or dexamethasone (0 -20 mg/kg i.p.) prior to CIS (20 mg/kg i.p.) in the least shrew, and the induced emesis was recorded for 60 minutes. CIS-induced vomiting was dose-dependently and significantly attenuated by individual administration of Δ 9 -THC (59-97% reductions) and tropisetron (79-100% attenuation), but not dexamethasone (26-40%), although a trend (p < .1) towards reduced vomiting frequency following DEX was noted. Low doses of Δ 9 -THC (0.25 or 0.5 mg/kg) when combined with low doses of tropisetron (0.025, 0.1, or 0.25 mg/kg) were more efficacious in reducing emesis frequency than when given individually, but Δ 9 -THC had no antiemetic interactions with DEX. However, no tested combination provided a significantly greater effect on the number of animals vomiting than their individually-administered counterparts. The modest interaction of Δ 9 -THC with tropisetron suggests they activate overlapping antiemetic mechanisms, while the lack of interaction with dexamethasone needs further clarification.

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“…These drugs have optimized the treatment of acute chemotherapy-induced nausea and vomiting, but their effect in delayed emesis is less pronounced. Corticosteroids add to the antiemetic effect of highdose metoclopramide [16,26], and the efficacy of the selective serotonin antagonists is increased by both steroids [8,22,36,37] and dopamine antagonists [7,19,21] ( Table 1). A natural continuation of the clinical research would be an investigation of the combination of a serotonin antagonist, a steroid and a dopamine antagonist, and such studies have been initiated.…”

Section: Past Developmentmentioning

confidence: 99%

New perspectives in antiemetic treatment

Herrstedt

1996

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Though antiemetic therapy has improved markedly in the past 15 years, patients still regard nausea and vomiting as two of the most distressing adverse events during chemotherapy. A major progress was the development of the serotonin3 (5-HT3) receptor antagonists. A possible antiemetic effect, achieved by interference with the "serotonergic system", is not restricted to antagonism at 5-HT3 receptors, however, but also includes agonism at 5-HT1A and 5-HT2 receptors, and serotonin synthesis inhibitors. The number of receptors thought to be involved in the emetic reflex has been augmented by neurokinin1 receptors with substance P as the preferred ligand. Animal studies have demonstrated a broad antiemetic profile of substance P antagonists. The somatostatin analogue octreotide has an antiemetic effect in patients with gastrointestinal obstruction, but has not been investigated against chemotherapy-induced emesis. The next few years will disclose, whether the efficacy and safety profiles of one or more of these drugs will make it clinically useful in the treatment of chemotherapy-induced nausea and vomiting.

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Efficacy and tolerability of tropisetron in comparison with a combination of tropisetron and dexamethasone in the control of nausea and vomiting induced by cisplatin-containing chemotherapy

Cited by 29 publications

References 12 publications

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

Comparison of three tropisetron-containing antiemetic regimens in the prophylaxis of acute and delayed chemotherapy-induced emesis and nausea

The antiemetic interaction of Δ9-tetrahydrocannabinol when combined with tropisetron or dexamethasone in the least shrew

New perspectives in antiemetic treatment

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