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Supportive Care in Cancer
Published in: Supportive Care in Cancer 3/2015

Open Access 01-03-2015 | Original Article

Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial

Authors: Harry Raftopoulos, William Cooper, Erin O’Boyle, Nashat Gabrail, Ralph Boccia, Richard J. Gralla

Published in: Supportive Care in Cancer | Issue 3/2015

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Abstract

Purpose

Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0–24 h) and delayed (24–120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC).

Methods

Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority to palonosetron for preventing delayed CINV following HEC. The primary efficacy end point was complete response (CR [using CI difference for APF530 − palonosetron]). A lower confidence bound greater than −15 % indicated noninferiority.

Results

In the modified intent-to-treat population (MEC = 634; HEC = 707), both APF530 doses were noninferior to palonosetron in preventing acute CINV after MEC (CRs 74.8 % [−9.8, 9.3] and 76.9 % [−7.5, 11.4], respectively, vs. 75.0 % palonosetron) and after HEC (CRs 77.7 % [−11.5, 5.5] and 81.3 % [-7.7, 8.7], respectively, vs. 80.7 % palonosetron). APF530 500 mg was noninferior to palonosetron in preventing delayed CINV after MEC (CR 58.5 % [−9.5, 12.1] vs. 57.2 % palonosetron) but not superior in preventing delayed CINV after HEC. Adverse events were generally mild and unrelated to treatment, the most common (excluding injection-site reactions) being constipation.

Conclusions

A single subcutaneous APF530 injection offers a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC.
Literature
1.
2.
Basch E, Prestrud AA, Hesketh PJ, Kris MG, Feyer PC, Somerfield MR, Chesney M, Clark-Snow RA, Flaherty AM, Freundlich B, Morrow G, Rao KV, Schwartz RN, Lyman GH (2011) Antiemetics: American society of clinical oncology clinical practice guideline update. J Clin Oncol 29:4189–4198PubMedCrossRef
3.
Roila F, Herrstedt J, Aapro M, Gralla RJ, Einhorn LH, Ballatori E, Bria E, Clark-Snow RA, Espersen BT, Feyer P, Grunberg SM, Hesketh PJ, Jordan K, Kris MG, Maranzano E, Molassiotis A, Morrow G, Olver I, Rapoport BL, Rittenberg C, Saito M, Tonato M, Warr D (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
4.
Hesketh PJ, Kris MG, Grunberg SM, Beck T, Hainsworth JD, Harker G, Aapro MS, Gandara D, Lindley CM (1997) Proposal for classifying the acute emetogenicity of cancer chemotherapy. J Clin Oncol 15:103–109PubMed
5.
Grunberg SM, Deuson RR, Mavros P, Geling O, Hansen M, Cruciani G, Daniele B, De Pourville G, Rubenstein EB, Daugaard G (2004) Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer 100:2261–2268
6.
Roila F, Warr D, Clark-Snow RA, Tonato M, Gralla RJ, Einhorn LH, Herrstedt J (2005) Delayed emesis: moderately emetogenic chemotherapy. Support Care Cancer 13:104–108PubMedCrossRef
7.
Geling O, Eichler HG (2005) Should 5-hydroxytryptamine-3 receptor antagonists be administered beyond 24 hours after chemotherapy to prevent delayed emesis? Systematic re-evaluation of clinical evidence and drug cost implications. J Clin Oncol 23:1289–1294PubMedCrossRef
8.
Aapro MS, Grunberg SM, Manikhas GM, Olivares G, Suarez T, Tjulandin SA, Bertoli LF, Yunus F, Morrica B, Lordick F, Macciocchi A (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 17:1441–1449PubMedCrossRef
9.
Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S (2003) Improved prevention of moderately emetogenic chemotherapy-induced nausea and vomiting with palonosetron, a pharmacologically novel 5-HT3 receptor antagonist: results of a phase III, single-dose trial versus dolasetron. Cancer 98:2473–2482PubMedCrossRef
10.
Gralla R, Lichinitser M, Van DV, Sleeboom H, Mezger J, Peschel C, Tonini G, Labianca R, Macciocchi A, Aapro M (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
11.
Saito M, Aogi K, Sekine I, Yoshizawa H, Yanagita Y, Sakai H, Inoue K, Kitagawa C, Ogura T, Mitsuhashi S (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 10:115–124PubMedCrossRef
12.
Roila F, Warr D, Aapro M, Clark-Snow RA, Einhorn L, Gralla RJ, Herrstedt J, Saito M, Tonato M (2011) Delayed emesis: moderately emetogenic chemotherapy (single-day chemotherapy regimens only). Support Care Cancer 19(Suppl 1):S57–S62PubMedCrossRef
13.
Rojas C, Thomas AG, Alt J, Stathis M, Zhang J, Rubenstein EB, Sebastiani S, Cantoreggi S, Slusher BS (2010) Palonosetron triggers 5-HT(3) receptor internalization and causes prolonged inhibition of receptor function. Eur J Pharmacol 626:193–199PubMedCrossRef
14.
Rojas C, Raje M, Tsukamoto T, Slusher BS (2013) Molecular mechanisms of 5-HT(3) and NK(1) receptor antagonists in prevention of emesis. Eur J Pharmacol 722:26–37
15.
16.
Hesketh PJ (1999) Defining the emetogenicity of cancer chemotherapy regimens: relevance to clinical practice. Oncologist 4:191–196PubMed
17.
Hochberg J (1988) A sharper Bonferroni procedure for multiple tests of significance. Biometrika 75:800–802CrossRef
18.
(2011) Kytril (granisetron hydrochloride) injection. Prescribing information. South San Francisco, CA: Genentech, Inc
19.
(2010) Kytril (granisetron hydrochloride) tablets oral solution. Prescribing information. Roche Pharmaceuticals, Nutley, NJ
20.
Rojas C, Li Y, Zhang J, Stathis M, Alt J, Thomas AG, Cantoreggi S, Sebastiani S, Pietra C, Slusher BS (2010) The antiemetic 5-HT3 receptor antagonist palonosetron inhibits substance P-mediated responses in vitro and in vivo. J Pharmacol Exp Ther 335:362–368PubMedCentralPubMedCrossRef
21.
Boccia R, Grunberg S, Franco-Gonzales E, Rubenstein E, Voisin D (2013) Efficacy of oral palonosetron compared to intravenous palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately emetogenic chemotherapy: a phase 3 trial. Support Care Cancer 21:1453–1460PubMedCentralPubMedCrossRef
Metadata
Title
Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial
Authors
Harry Raftopoulos
William Cooper
Erin O’Boyle
Nashat Gabrail
Ralph Boccia
Richard J. Gralla
Publication date
01-03-2015
Publisher
Springer Berlin Heidelberg
Published in
Supportive Care in Cancer / Issue 3/2015
Print ISSN: 0941-4355
Electronic ISSN: 1433-7339
DOI
https://doi.org/10.1007/s00520-014-2400-3

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