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Published in: Supportive Care in Cancer 12/2012

Open Access 01-12-2012 | Original Article

Antiemetic efficacy of single-dose palonosetron and dexamethasone in patients receiving multiple cycles of multiple day-based chemotherapy

Authors: Vito Lorusso, Marianna Giampaglia, Luciana Petrucelli, Valeria Saracino, Tania Perrone, Antonio Gnoni

Published in: Supportive Care in Cancer | Issue 12/2012

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Abstract

Introduction

The goal of pharmacological prophylaxis of chemotherapy-induced nausea and vomiting (CINV) should be the elimination of both nausea and vomiting symptoms during all planned chemotherapy cycles. The aim of this study was to assess the efficacy of a single dose of palonosetron and dexamethasone to prevent CINV and to guarantee an adequate food intake (FI) in patients receiving several cycles of multiple day-based chemotherapy (MD-CT).

Methods

Patients with advanced cancer but without a compromised nutritional status (bone mass index ≥ 18.5) were treated with 0.25 mg palonosetron plus 20 mg dexamethasone before MD-CT. The MD-CT regimen was either epirubicin plus ifosfamide or paclitaxel plus cisplatin and ifosfamide. Nausea, vomiting, and FI were monitored in a 7-day diary. Complete response (CR: no vomiting and no rescue therapy) was the primary endpoint, while complete control (CC: CR and no more than mild nausea) and the evaluation of FI were secondary endpoints. The endpoints were evaluated during the overall timescale (0–168 h) of the chemotherapy regimen.

Results

Fifty patients were enrolled, 80% of whom achieved CR and 78% achieved CC. During the six chemotherapy cycles, CR and CC ranged from 76% to 88% and from 62% to 88%, respectively. Moreover, patients with CR had a significantly (p < 0.0001) higher weekly food intake compared with patients not achieving CR.

Conclusions

This trial was the first to assess the efficacy of palonosetron and dexamethasone for the prevention of both nausea and vomiting in patients receiving multiple cycles of MD-CT. In this trial, the ability of patients to intake an adequate amount of food each week was correlated with nausea, thus providing clinicians with an objective parameter for the measurement of the effects of nausea. A single dose of palonosetron and dexamethasone was able to prevent CINV in most patients receiving 3 days of chemotherapy during all planned chemotherapy cycles.
Literature
1.
2.
go back to reference De Wit R, Van Den Berg H, Burghouts J et al (1998) Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles. Brit J Cancer 77(9):1487–1491PubMedCrossRef De Wit R, Van Den Berg H, Burghouts J et al (1998) Initial high anti-emetic efficacy of granisetron with dexamethasone is not maintained over repeated cycles. Brit J Cancer 77(9):1487–1491PubMedCrossRef
3.
go back to reference Sigsgaard T, Herrstedt J, Handberg J et al (2001) Ondansetron plus metopimazine compared with ondansetron plus metopimazine plus prednisolone as antiemetic prophylaxis in patients receiving multiple cycles of moderately emetogenic chemotherapy. J Clin Oncol 19(7):2091–2097PubMed Sigsgaard T, Herrstedt J, Handberg J et al (2001) Ondansetron plus metopimazine compared with ondansetron plus metopimazine plus prednisolone as antiemetic prophylaxis in patients receiving multiple cycles of moderately emetogenic chemotherapy. J Clin Oncol 19(7):2091–2097PubMed
4.
go back to reference De Wit R, Herrstedt J, Rapoport B et al (2003) Addition of the oral NK 1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 21:4105–4111PubMedCrossRef De Wit R, Herrstedt J, Rapoport B et al (2003) Addition of the oral NK 1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy. J Clin Oncol 21:4105–4111PubMedCrossRef
5.
go back to reference Celio L, Denaro A, Canova S, Gevorgyan A, Bajetta E (2008) Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting. Tumori 94:447–452PubMed Celio L, Denaro A, Canova S, Gevorgyan A, Bajetta E (2008) Clinical update on palonosetron in the management of chemotherapy-induced nausea and vomiting. Tumori 94:447–452PubMed
6.
go back to reference Navari RM (2007) Prevention of emesis from multiple-day and high-dose chemotherapy regimens. J Natl Compr Cancer Netw 5(1):51–59 Navari RM (2007) Prevention of emesis from multiple-day and high-dose chemotherapy regimens. J Natl Compr Cancer Netw 5(1):51–59
7.
go back to reference Saito M, Tsukuda M (2010) Review of palonosetron: emerging data distinguishing it as a novel 5-HT 3 receptor antagonist for chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother 11(6):1003–1014PubMedCrossRef Saito M, Tsukuda M (2010) Review of palonosetron: emerging data distinguishing it as a novel 5-HT 3 receptor antagonist for chemotherapy-induced nausea and vomiting. Expert Opin Pharmacother 11(6):1003–1014PubMedCrossRef
9.
go back to reference Roila F, Herrstedt J, Aapro M et al (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(suppl 5):v232–v243PubMedCrossRef Roila F, Herrstedt J, Aapro M et al (2010) Guideline update for MASCC and ESMO in the prevention of chemotherapy- and radiotherapy-induced nausea and vomiting: results of the Perugia consensus conference. Ann Oncol 21(suppl 5):v232–v243PubMedCrossRef
10.
go back to reference Eisenberg P, Figuero-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A et al (2003) Improved prevention of moderately emetogenic chemotherapy induced nausea and vomiting with palonosetron, a pharmacologically novel 5HT3 receptor antagonist. Results of a phase III, single dose trial versus dolasetron. Cancer 98(11):2473–2482PubMedCrossRef Eisenberg P, Figuero-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A et al (2003) Improved prevention of moderately emetogenic chemotherapy induced nausea and vomiting with palonosetron, a pharmacologically novel 5HT3 receptor antagonist. Results of a phase III, single dose trial versus dolasetron. Cancer 98(11):2473–2482PubMedCrossRef
11.
go back to reference Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C et al (2003) Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 14:1570–1577PubMedCrossRef Gralla R, Lichinitser M, Van Der Vegt S, Sleeboom H, Mezger J, Peschel C et al (2003) Palonosetron improves prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: results of a double-blind randomized phase III trial comparing single doses of palonosetron with ondansetron. Ann Oncol 14:1570–1577PubMedCrossRef
12.
go back to reference Rubenstein EB, Gralla RJ, Eisenberg P (2003) Palonosetron (PALO) compared with ondansetron (OND) or dolasetron (DOL) for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Combined results of two phase III trials. Proc Am Soc Clin Oncol 22:729–A2932 Rubenstein EB, Gralla RJ, Eisenberg P (2003) Palonosetron (PALO) compared with ondansetron (OND) or dolasetron (DOL) for prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV). Combined results of two phase III trials. Proc Am Soc Clin Oncol 22:729–A2932
13.
go back to reference Aapro MS, Grunberg SM, Manikhas GM et al (2006) A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 17(9):1441–1449PubMedCrossRef Aapro MS, Grunberg SM, Manikhas GM et al (2006) A phase III, double-blind, randomized trial of palonosetron compared with ondansetron in preventing chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy. Ann Oncol 17(9):1441–1449PubMedCrossRef
14.
go back to reference Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H et al (2009) Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 10(2):115–124PubMedCrossRef Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H et al (2009) Palonosetron plus dexamethasone versus granisetron plus dexamethasone for prevention of nausea and vomiting during chemotherapy: a double-blind, double-dummy, randomised, comparative phase III trial. Lancet Oncol 10(2):115–124PubMedCrossRef
15.
go back to reference Warr DG, Hesketh PJ, Gralla RJ et al (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23(12):2822–2830PubMedCrossRef Warr DG, Hesketh PJ, Gralla RJ et al (2005) Efficacy and tolerability of aprepitant for the prevention of chemotherapy-induced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol 23(12):2822–2830PubMedCrossRef
16.
go back to reference Khojasteh A, Khojasteh A, Thornburg BG et al (2009) Casopitant: a new warrior in the antiemetic crusade. Expert Opin Pharmacother 10(8):1367–1376PubMedCrossRef Khojasteh A, Khojasteh A, Thornburg BG et al (2009) Casopitant: a new warrior in the antiemetic crusade. Expert Opin Pharmacother 10(8):1367–1376PubMedCrossRef
17.
go back to reference Lorusso V, Spedicato A, Petrucelli L et al (2009) Single dose of palonosetron plus dexamethasone to control nausea, vomiting and to warrant an adequate food intake in patients treated with highly emetogenic chemotherapy (HEC). Preliminary results. Support Care Cancer 17(12):1469–1473PubMedCrossRef Lorusso V, Spedicato A, Petrucelli L et al (2009) Single dose of palonosetron plus dexamethasone to control nausea, vomiting and to warrant an adequate food intake in patients treated with highly emetogenic chemotherapy (HEC). Preliminary results. Support Care Cancer 17(12):1469–1473PubMedCrossRef
18.
go back to reference Cartmell AD, Ferguson S, Yanagihara R et al (2003) Protection against chemotherapy-induced nausea and vomiting (CINV) is maintained over multiple cycles of moderately or highly emetogenic chemotherapy by palonosetron (PALO), a potent 5-HT3 receptor antagonist (RA). Proc Am Soc Clin Oncol 22: 2003 (abstr 3041) Cartmell AD, Ferguson S, Yanagihara R et al (2003) Protection against chemotherapy-induced nausea and vomiting (CINV) is maintained over multiple cycles of moderately or highly emetogenic chemotherapy by palonosetron (PALO), a potent 5-HT3 receptor antagonist (RA). Proc Am Soc Clin Oncol 22: 2003 (abstr 3041)
19.
go back to reference Lindley C, McCune JS, Thomason TE, Lauder D, Sauls A, Adkins S et al (1999) Perception of chemotherapy side effects cancer versus non cancer patients. Cancer Pract 7:59–65PubMedCrossRef Lindley C, McCune JS, Thomason TE, Lauder D, Sauls A, Adkins S et al (1999) Perception of chemotherapy side effects cancer versus non cancer patients. Cancer Pract 7:59–65PubMedCrossRef
20.
go back to reference Basch E (2010) The missing voice of patients in drug-safety reporting. N Engl J Med 362:10CrossRef Basch E (2010) The missing voice of patients in drug-safety reporting. N Engl J Med 362:10CrossRef
21.
go back to reference Einhorn LH, Brames MJ, Dreicer R et al (2007) Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer. Support Care Cancer 15:1293–1300PubMedCrossRef Einhorn LH, Brames MJ, Dreicer R et al (2007) Palonosetron plus dexamethasone for prevention of chemotherapy-induced nausea and vomiting in patients receiving multiple-day cisplatin chemotherapy for germ cell cancer. Support Care Cancer 15:1293–1300PubMedCrossRef
22.
go back to reference Rozzi A, Nardoni CA, Corona M et al (2009) Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study. Support Care Cancer 19:697–701CrossRef Rozzi A, Nardoni CA, Corona M et al (2009) Palonosetron for the prevention of chemotherapy-induced nausea and vomiting in glioblastoma patients treated with temozolomide: a phase II study. Support Care Cancer 19:697–701CrossRef
23.
go back to reference Musso M, Scalone R, Bonanno V, Crescimanno A, Polizzi V, Porretto F et al (2009) Palonosetron (Aloxi) and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving multiple-day chemotherapy. Support Care Cancer 17(2):205–209PubMedCrossRef Musso M, Scalone R, Bonanno V, Crescimanno A, Polizzi V, Porretto F et al (2009) Palonosetron (Aloxi) and dexamethasone for the prevention of acute and delayed nausea and vomiting in patients receiving multiple-day chemotherapy. Support Care Cancer 17(2):205–209PubMedCrossRef
24.
go back to reference Aapro M, Fabi A, Nolè F et al (2010) Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol May 21(5):1083–1088, Epub 2010 Jan 15CrossRef Aapro M, Fabi A, Nolè F et al (2010) Double-blind, randomised, controlled study of the efficacy and tolerability of palonosetron plus dexamethasone for 1 day with or without dexamethasone on days 2 and 3 in the prevention of nausea and vomiting induced by moderately emetogenic chemotherapy. Ann Oncol May 21(5):1083–1088, Epub 2010 Jan 15CrossRef
25.
go back to reference Celio L, Frustaci S, Denaro A, et al (2010 June 25) Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial. Support Care Cancer 19:1217-1225 Celio L, Frustaci S, Denaro A, et al (2010 June 25) Palonosetron in combination with 1-day versus 3-day dexamethasone for prevention of nausea and vomiting following moderately emetogenic chemotherapy: a randomized, multicenter, phase III trial. Support Care Cancer 19:1217-1225
26.
go back to reference Vardy J, Chiew KS, Galica J et al (2006) Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer 94:1011–1015 Vardy J, Chiew KS, Galica J et al (2006) Side effects associated with the use of dexamethasone for prophylaxis of delayed emesis after moderately emetogenic chemotherapy. Br J Cancer 94:1011–1015
27.
28.
go back to reference Stoltz R, Cyong JC, Shah A et al (2004) Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol 44:520–531PubMedCrossRef Stoltz R, Cyong JC, Shah A et al (2004) Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol 44:520–531PubMedCrossRef
29.
go back to reference Wong EH, Clark R, Leung E et al (1995) The interaction of RS 25259–197, a potent and selective antagonist, with 5-HT3 receptors, in vitro. Br J Pharmacol 114(4):851–859PubMedCrossRef Wong EH, Clark R, Leung E et al (1995) The interaction of RS 25259–197, a potent and selective antagonist, with 5-HT3 receptors, in vitro. Br J Pharmacol 114(4):851–859PubMedCrossRef
30.
go back to reference Rojas C, Stathis M, Thomas AG et al (2008) Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg 107:469–478PubMedCrossRef Rojas C, Stathis M, Thomas AG et al (2008) Palonosetron exhibits unique molecular interactions with the 5-HT3 receptor. Anesth Analg 107:469–478PubMedCrossRef
31.
go back to reference Rojas C, Thomas AG, Alt J et al (2010) Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol 626(2–3):193–199PubMedCrossRef Rojas C, Thomas AG, Alt J et al (2010) Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol 626(2–3):193–199PubMedCrossRef
Metadata
Title
Antiemetic efficacy of single-dose palonosetron and dexamethasone in patients receiving multiple cycles of multiple day-based chemotherapy
Authors
Vito Lorusso
Marianna Giampaglia
Luciana Petrucelli
Valeria Saracino
Tania Perrone
Antonio Gnoni
Publication date
01-12-2012
Publisher
Springer-Verlag
Published in
Supportive Care in Cancer / Issue 12/2012
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-012-1469-9

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