Management of platinum-based chemotherapy-induced acute nausea and vomiting: is there a superior serotonin receptor antagonist?

Abstract

Objective. The last decade has witnessed the great impact of 5-hydroxytryptamine-3 receptor (5-HT3) antagonists in revolutionizing the management of platinum-based chemotherapy–induced acute nausea and vomiting (CINV). However, despite the availability of a variety of 5-HT3 antagonists, little data is published to support superiority of one drug over another, leaving the choice of serotonin receptor antagonist largely empirical. The National Comprehensive Cancer Network and American Society of Clinical Oncology guidelines for management of chemotherapy-associated nausea and vomiting clearly endorse the use of serotonin receptor antagonist; however, no single agent is preferred over the rest.

Methods. Data for patients (n¼159) receiving platinum-based chemotherapy regimens were retrospectively collected. Patients getting 5-HT3 antagonists without steroids or those with known history of brain metastasis, gastroparesis, and intestinal obstruction were not eligible for the study. Patient characteristics including age, gender, primary diagnosis, history of heavy alcohol intake, chemotherapy regimen administered, number of cycles, and Eastern Cooperative Oncology Group performance status at the start of therapy were noted. Primary outcome was the complete control of platinum-induced acute nausea and vomiting. Secondary outcome measures included control of >grade 1 nausea or vomiting, comparison of two doses of dexamethasone, and antiemetic efficacy among various platinum drugs. National Cancer Institute Common Toxicity Criteria version 2.0 was used to assess toxicity.

Results. A total of 126 patients received 369 cycles of platinum-based therapy. Dolasetron (n¼157), granisetron (n¼81), and ondansetron (n¼131) achieved complete control of vomiting in 89.8, 95.5, and 92.3% (p¼0.67) of cycles, respectively. Respectively, complete nausea control was observed in 68.1, 75.3 and, 69.4% (p¼0.50). Dexamethasone 20 mg was not superior to 10 mg in complete control of nausea and vomiting (p¼0.15 and p¼0.63, respectively). However, complete nausea control was significantly better in the subgroup of patients getting cisplatin-compared with carboplatin-based regimens (78.8% vs. 67.7%, p50.05).

Conclusion. No significant difference exists in the antiemetic efficacy of the three 5-HT3 antagonists studied in controlling CINV when administered in combination with dexamethasone. Choice of antiemetic regimen should therefore be based on drug cost.

Keywords

acute emesis chemotherapy-induced acute nausea and vomiting,dolasetron granisetron ondansetron

Get full access to this article

View all access options for this article.

References

Hesketh PJ , Harvey WH , Harker WG , et al. A randomized, double-blind comparison of intravenous ondansetron alone and in combination with intravenous dexamethasone in the prevention of high-dose cisplatin-induced emesis . J Clin Oncol 1994; 12: 596—600 .

Frederick S. Chemotherapy-induced nausea and vomiting: The importance of acute antiemetic control . The Oncologist 2003; 8: 187—98 .

Hesketh PJ Comparative review of 5-HT3 receptor antagonists in the treatment of acute chemotherapy-induced nausea and vomiting . Cancer Invest 2000; 18: 163—73 .

Doherty KM Closing the gap in prophylactic antiemetic therapy: patient factors in calculating the emetogenic potential of chemotherapy . Clin J Oncol Nurs 1999; 3: 113—19 .

The Italian Multicenter Study Group. A double-blind randomized study comparing intramuscular (i.m) granisetron with i.m granisetron with dexamethasone in the prevention of delayed emesis induced by cisplatin . Anticancer Drugs 1999 ; 10: 465—70 .

Coates A. , Abraham S. , Kaye SB , Sowerbutts T. , Frewin C. , Fox RM , et al. On the receiving end — patient perception of the side effects of cancer chemotherapy . Eur J Cancer Oncol 1983; 19: 203—8 .

Fetting JH , Grochow LB , Folstein MF , Ettinger DS , Colvin M. The course of nausea and vomiting after high dose cyclophosphamide . Cancer Treat Rep 1982; 66: 1487—93 .

Roemling RV , Christian NP , Hrushesky WJ Lack of antiemetic effect of high dose metoclopramide . J clin Oncol 1985; 3: 1273—6 .

Cindy LD , Andrew JC , Alicia Paf , Douglas RE , Sharon OB Antiemetic effectiveness of ondansetron and granisetron in patients with breast cancer treated with cyclophosphamide . Am J Healthc Syst Pharm 2004; 61: 781—86 .

10.

Grunberg SM , Hesketh PJ Control of chemotherapy induced emesis . N Engl J Med 1993; 329: 1790—6 .

11.

Verweij J. , de Wit R. , de Mulder Phm. Optimal control of acute cisplatin-induced emesis . Oncology 1996; 53: 56—64 .

12.

De Mulder Phh , Verweij J. Prevention of acute cisplatin-induced nausea and vomiting. In: Tonato M. , ed. Antiemetics in the supportive care of cancer patients 1996; Springer-Verlag , 1996: 49—60.

13.

Smyth JF , Coleman RE , Nicolson N. , et al. Does dexamethasone enhance control of acute cisplatin induced emesis by ondansetron? Br Med J 1991; 303: 1423—6 .

14.

Roila F. , Tonato M. , Cognetti F. , et al. Prevention of cisplatin-induced emesis: a double-blind multicenter randomized crossover study comparing ondansetron and ondansetron plus dexamethasone . J Clin Oncol 1991; 9: 675—8 .

15.

Del Favero A , Roila F. , Tonato M. Reducing chemotherapy-induced nausea and vomiting. Current perspectives and future possibilities . Drug Saf 1993; 9: 410—28 .

16.

Andrews PL , Bhandari P. , Davey PT , et al. Are all 5-HT3 receptor antagonists the same? Eur J Cancer 1992; 28A: S2—S6 .

17.

Hesketh P. , Navari R. , Grote T. , et al. Double-blind, randomized comparison of the antiemetic efficacy of intravenous dolasetron mesylate and intravenous ondansetron in the prevention of acute cisplatin-induced emesis in the patients with cancer . Cancer J 1996; 14: 2242—49 .

18.

Alvarez O. , Freeman A. , Bedros A. , Call SK , Volsch J. , Kalbermatter O. , Halverson J. , Convy L. , Cook L. , Mick K. , et al. Randomized double-blind crossover ondansetron-dexamethasone versus ondansetron-placebo study for the treatment of chemotherapy-induced nausea and vomiting in pediatric patients with malignancies . J Pediatr Hematol/Oncol 1995; 17: 145—50 .

19.

Italian Group of Antiemetic Research. Ondansetron versus granisetron both combined with dexamethasone, in the prevention of cisplatin-induced emesis . Ann Oncol 1995 ; 6: 805—10 .

20.

Carmichael J. , Bessell EM , Harris AL , Hutcheon AW , Dawes PJ , Daniels S. , Bessel EM Comparison of granisetron alone and granisetron plus dexamethasone in the prophylaxis of cytotoxic-induced emesis . Br J Cancer 1994; 70: 1161—64 .

21.

Fauser A. , Pizzocaro G. , Schueller J. , Khayat D. , Wilkinson P. A double-blind, randomized, parallel study comparing intravenous dolasetron plus dexamethasone and intravenous dolasetron alone for the management of fractionated cisplatin-related nausea and vomiting . Support Care Cancer 2000; 8: 49—54 .

22.

Mantovani G. , Maccio A. , Bianchi A. , Curreli L. , Ghiani M. , Proto E. , Santona MC Comparison of granisetron, ondansetron, and tropisetron in the prophylaxis of acute nausea and vomiting induced by cisplatin for the treatment of head and neck cancer: a randomized controlled trial . Cancer 1996; 77: 941—48 .