Effectiveness of palonosetron versus granisetron in preventing chemotherapy-induced nausea and vomiting: a systematic review and meta-analysis.

Publisher: Springer Country of Publication: Germany NLM ID: 1256165 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1432-1041 (Electronic) Linking ISSN: 00316970 NLM ISO Abbreviation: Eur J Clin Pharmacol Subsets: MEDLINE

Original Publication: Berlin, New York, Springer.

Antiemetics/*therapeutic use ; Antineoplastic Agents/*therapeutic use ; Granisetron/*therapeutic use ; Nausea/*drug therapy ; Palonosetron/*therapeutic use ; Vomiting/*drug therapy; Antineoplastic Agents/adverse effects ; Granisetron/adverse effects ; Humans ; Nausea/chemically induced ; Palonosetron/adverse effects ; Quality of Life ; Randomized Controlled Trials as Topic ; Serotonin 5-HT3 Receptor Antagonists/therapeutic use ; Vomiting/chemically induced

Purpose: Chemotherapy-induced nausea and vomiting (CINV) commonly occurs after chemotherapy, adversely affecting patients' quality of life. Recently, studies have shown inconsistent antiemetic effects of two common 5-hydroxytryptamine 3 receptor antagonists, namely, palonosetron and granisetron. Therefore, we conducted a meta-analysis to evaluate the effectiveness of palonosetron versus granisetron in preventing CINV.
Methods: Relevant studies were obtained from PubMed, Embase, and Cochrane databases. The primary outcome was the complete response (CR) rate. Secondary outcomes were headache and constipation events.
Results: In total, 12 randomized controlled trials and five retrospective studies were reviewed. Palonosetron was consistently statistically superior to granisetron in all phases in terms of the CR rate (acute phases: odds ratio [OR] = 1.28, 95% confidence interval [CI] = 1.06-1.54; delayed phases: OR = 1.38, 95% CI = 1.13-1.69; and overall phases: OR = 1.37, 95% CI = 1.17-1.60). Moreover, a non-significant difference was found between the two groups in terms of the headache event, but the occurrence of the constipation event was lower in the granisetron group than in the palonosetron group.
Conclusion: Palonosetron showed a higher protective efficacy in all phases of CINV prevention, especially in delayed phases, and no relatively severe adverse effects were observed.
(© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Network NCC (2020) Antiemesis (Version 2.2020). https://www.nccn.org/professionals/physician_gls/pdf/antiemesis.pdf . Accessed 23 April 2020.
Osoba D, Zee B, Pater J, Warr D, Latreille J, Kaizer L (1997) Determinants of postchemotherapy nausea and vomiting in patients with cancer. Quality of life and symptom control committees of the national cancer institute of canada clinical trials group. J Clin Oncol 15 (1):116–123. https://doi.org/10.1200/JCO.1997.15.1.116.
Hasler WL (1999) Serotonin receptor physiology: relation to emesis. Dig Dis Sci 44(8 Suppl):108S-113S. (PMID: 10490049)
Jantunen IT, Kataja VV, Muhonen TT (1997) An overview of randomised studies comparing 5-HT3 receptor antagonists to conventional anti-emetics in the prophylaxis of acute chemotherapy-induced vomiting. Eur J Cancer 33(1):66–74. https://doi.org/10.1016/s0959-8049(96)00276-6. (PMID: 10.1016/s0959-8049(96)00276-69071902)
Jordan K, Hinke A, Grothey A, Voigt W, Arnold D, Wolf HH, Schmoll HJ (2007) A meta-analysis comparing the efficacy of four 5-HT3-receptor antagonists for acute chemotherapy-induced emesis. Support Care Cancer 15(9):1023–1033. https://doi.org/10.1007/s00520-006-0186-7. (PMID: 10.1007/s00520-006-0186-717205281)
Navari RM, Province PS (2006) Emerging drugs for chemotherapy-induced emesis. Expert Opin Emerg Drugs 11(1):137–151. https://doi.org/10.1517/14728214.11.1.137. (PMID: 10.1517/14728214.11.1.13716503832)
Stoltz R, Cyong JC, Shah A, Parisi S (2004) Pharmacokinetic and safety evaluation of palonosetron, a 5-hydroxytryptamine-3 receptor antagonist, in U.S. and Japanese healthy subjects. J Clin Pharmacol 44 (5):520–531. https://doi.org/10.1177/0091270004264641.
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(2):115–124. https://doi.org/10.1016/s1470-2045(08)70313-9. (PMID: 10.1016/s1470-2045(08)70313-919135415)
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(9):1441–1449. https://doi.org/10.1093/annonc/mdl137. (PMID: 10.1093/annonc/mdl13716766588)
Eisenberg P, Figueroa-Vadillo J, Zamora R, Charu V, Hajdenberg J, Cartmell A, Macciocchi A, Grunberg S, Palonosetron Study G (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(11):2473–2482. https://doi.org/10.1002/cncr.11817. (PMID: 10.1002/cncr.11817)
Botrel TE, Clark OA, Clark L, Paladini L, Faleiros E, Pegoretti B (2011) Efficacy of palonosetron (PAL) compared to other serotonin inhibitors (5-HT3R) in preventing chemotherapy-induced nausea and vomiting (CINV) in patients receiving moderately or highly emetogenic (MoHE) treatment: systematic review and meta-analysis. Support Care Cancer 19(6):823–832. https://doi.org/10.1007/s00520-010-0908-8. (PMID: 10.1007/s00520-010-0908-820495832)
Jin Y, Sun W, Gu D, Yang J, Xu Z, Chen J (2013) Comparative efficacy and safety of palonosetron with the first 5-HT3 receptor antagonists for the chemotherapy-induced nausea and vomiting: a meta-analysis. Eur J Cancer Care (Engl) 22(1):41–50. https://doi.org/10.1111/j.1365-2354.2012.01353.x. (PMID: 10.1111/j.1365-2354.2012.01353.x)
Popovic M, Warr DG, Deangelis C, Tsao M, Chan KK, Poon M, Yip C, Pulenzas N, Lam H, Zhang L, Chow E (2014) Efficacy and safety of palonosetron for the prophylaxis of chemotherapy-induced nausea and vomiting (CINV): a systematic review and meta-analysis of randomized controlled trials. Support Care Cancer 22(6):1685–1697. https://doi.org/10.1007/s00520-014-2175-6. (PMID: 10.1007/s00520-014-2175-624590374)
van der Vorst MJ, Neefjes EC, Konings IR, Verheul HM (2015) Prophylactic treatment for delayed chemotherapy-induced nausea and vomiting after non-AC based moderately emetogenic chemotherapy: a systematic review of randomized controlled trials. Support Care Cancer 23(8):2499–2506. https://doi.org/10.1007/s00520-015-2778-6. (PMID: 10.1007/s00520-015-2778-6260414804483187)
Hesketh PJ, Kris MG, Basch E, Bohlke K, Barbour SY, Clark-Snow RA, Danso MA, Dennis K, Dupuis LL, Dusetzina SB, Eng C, Feyer PC, Jordan K, Noonan K, Sparacio D, Somerfield MR, Lyman GH (2017) Antiemetics: American Society of Clinical Oncology Clinical Practice Guideline update. J Clin Oncol 35(28):3240–3261. https://doi.org/10.1200/JCO.2017.74.4789. (PMID: 10.1200/JCO.2017.74.478928759346)
Chow R, Warr DG, Navari RM, Tsao M, Popovic M, Chiu L, Milakovic M, Lam H, DeAngelis C (2018) Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis. Support Care Cancer 26(8):2519–2549. https://doi.org/10.1007/s00520-018-4237-7. (PMID: 10.1007/s00520-018-4237-729796708)
Gamble M, Carroll E, Wright GC, Glode AE (2020) Comparison of two different intravenous serotonin antagonists used for chemotherapy-induced nausea and vomiting prophylaxis in patients treated with moderately emetogenic risk regimens: a retrospective analysis from a large academic medical center. J Oncol Pharm Pract:1078155220938847. https://doi.org/10.1177/1078155220938847.
Matsumoto K, Takahashi M, Sato K, Osaki A, Takano T, Naito Y, Matsuura K, Aogi K, Fujiwara K, Tamura K, Baba M, Tokunaga S, Hirano G, Imoto S, Miyazaki C, Yanagihara K, Imamura CK, Chiba Y, Saeki T (2020) A double-blind, randomized, multicenter phase 3 study of palonosetron vs granisetron combined with dexamethasone and fosaprepitant to prevent chemotherapy-induced nausea and vomiting in patients with breast cancer receiving anthracycline and cyclophosphamide. Cancer Med 9(10):3319–3327. https://doi.org/10.1002/cam4.2979. (PMID: 10.1002/cam4.2979321685517221309)
Araz M, Karaagac M, Korkmaz L, Koral L, Inci F, Beypinar I, Uysal M, Artac M (2019) Comparison of palonosetron and granisetron in triplet antiemetic therapy in nonmetastatic breast cancer patients receiving high emetogenic chemotherapy: a multicenter, prospective, and observational study. Cancer Chemother Pharmacol 83(6):1091–1097. https://doi.org/10.1007/s00280-019-03831-4. (PMID: 10.1007/s00280-019-03831-430963213)
Higgins JP, Altman DG, Gotzsche PC, Juni P, Moher D, Oxman AD, Savovic J, Schulz KF, Weeks L, Sterne JA, Cochrane Bias Methods G, Cochrane Statistical Methods G (2011) The Cochrane Collaboration’s tool for assessing risk of bias in randomised trials. BMJ 343:d5928. https://doi.org/10.1136/bmj.d5928. (PMID: 10.1136/bmj.d592831962453196245)
Sterne JA, Hernan MA, Reeves BC, Savovic J, Berkman ND, Viswanathan M, Henry D, Altman DG, Ansari MT, Boutron I, Carpenter JR, Chan AW, Churchill R, Deeks JJ, Hrobjartsson A, Kirkham J, Juni P, Loke YK, Pigott TD, Ramsay CR, Regidor D, Rothstein HR, Sandhu L, Santaguida PL, Schunemann HJ, Shea B, Shrier I, Tugwell P, Turner L, Valentine JC, Waddington H, Waters E, Wells GA, Whiting PF, Higgins JP (2016) ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 355:i4919. https://doi.org/10.1136/bmj.i4919. (PMID: 10.1136/bmj.i4919277333545062054)
McGuinness LA, Higgins JPT (2020) Risk-of-bias VISualization (robvis): an R package and Shiny web app for visualizing risk-of-bias assessments. Res Synth Methods. https://doi.org/10.1002/jrsm.1411. (PMID: 10.1002/jrsm.141132336025)
GRADEpro GDT (2020) GRADEpro Guideline Development Tool [Software]. McMaster University. (developed by Evidence Prime, Inc.). Available from https://gradepro.org.
Common Terminology Criteria for Adverse Events (CTCAE). (2017). https://ctep.cancer.gov/protocolDevelopment/electronic_applications/docs/CTCAE_v5_Quick_Reference_8.5x11.pdf . Accessed 15 Nov 2020.
Liberati A, Altman DG, Tetzlaff J, Mulrow C, Gotzsche PC, Ioannidis JP, Clarke M, Devereaux PJ, Kleijnen J, Moher D (2009) The PRISMA statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions: explanation and elaboration. BMJ 339:b2700. https://doi.org/10.1136/bmj.b2700. (PMID: 10.1136/bmj.b2700196225522714672)
DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7(3):177–188. https://doi.org/10.1016/0197-2456(86)90046-2. (PMID: 10.1016/0197-2456(86)90046-2)
Huang J, Wang XJ, Yu D, Jin YN, Zhen LZ, Xu N, Liu W, Deng YC, Wu SX, He J (2013) The effect of palonosetron hydrochloride in the prevention of chemotherapy-induced moderate and severe nausea and vomiting. Exp Ther Med 5(5):1418–1426. https://doi.org/10.3892/etm.2013.996. (PMID: 10.3892/etm.2013.996237378923671900)
Kimura H, Yamamoto N, Shirai T, Nishida H, Hayashi K, Tanzawa Y, Takeuchi A, Igarashi K, Inatani H, Shimozaki S, Kato T, Aoki Y, Higuchi T, Tsuchiya H (2015) Efficacy of triplet regimen antiemetic therapy for chemotherapy-induced nausea and vomiting (CINV) in bone and soft tissue sarcoma patients receiving highly emetogenic chemotherapy, and an efficacy comparison of single-shot palonosetron and consecutive-day granisetron for CINV in a randomized, single-blinded crossover study. Cancer Med 4(3):333–341. https://doi.org/10.1002/cam4.373. (PMID: 10.1002/cam4.37325533447)
Murakami M, Hashimoto H, Yamaguchi K, Yamaguchi I, Senba S, Siraishi T (2014) Effectiveness of palonosetron for preventing delayed chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy in patients with gastrointestinal cancer. Support Care Cancer 22(4):905–909. https://doi.org/10.1007/s00520-013-2046-6. (PMID: 10.1007/s00520-013-2046-624240649)
Ohzawa H, Miki A, Hozumi Y, Miyazaki C, Sagara Y, Tanaka Y, Shiba S, Joutoku H, Sakuragi M, Takehara M, Sakuma Y, Nishimura W, Fujii H, Yasuda Y (2015) Comparison between the antiemetic effects of palonosetron and granisetron in breast cancer patients treated with anthracycline-based regimens. Oncol Lett 9(1):119–124. https://doi.org/10.3892/ol.2014.2640. (PMID: 10.3892/ol.2014.264025435944)
Raftopoulos H, Cooper W, O’Boyle E, Gabrail N, Boccia R, Gralla RJ (2015) 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. Support Care Cancer 23(3):723–732. https://doi.org/10.1007/s00520-014-2400-3. (PMID: 10.1007/s00520-014-2400-325179689)
Roscoe JA, Heckler CE, Morrow GR, Mohile SG, Dakhil SR, Wade JL, Kuebler JP (2012) Prevention of delayed nausea: a University of Rochester Cancer Center Community Clinical Oncology Program study of patients receiving chemotherapy. J Clin Oncol 30(27):3389–3395. https://doi.org/10.1200/JCO.2011.39.8123. (PMID: 10.1200/JCO.2011.39.8123229156573438235)
Sato Y, Hayakawa Y, Tatematsu M, Muro K, Noma H, Okamoto H (2012) Antiemetic effect of palonosetron in advanced colorectal cancer patients receiving mFOLFOX6 and FOLFIRI: a retrospective survey. Gan To Kagaku Ryoho 39(8):1215–1219. (PMID: 22902445)
Sayantani Ghosh SD (2010) Comparing different antiemetic regimens for chemotherapy induced nausea and vomiting. International Journal of Collaborative Research on Internal Medicine & Public Health 2(5):142–156.
Seol YM, Kim HJ, Choi YJ, Lee EM, Kim YS, Oh SY, Koh SJ, Baek JH, Lee WS, Joo YD, Lee HG, Yun EY, Chung JS (2016) Transdermal granisetron versus palonosetron for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy: a multicenter, randomized, open-label, cross-over, active-controlled, and phase IV study. Support Care Cancer 24(2):945–952. https://doi.org/10.1007/s00520-015-2865-8. (PMID: 10.1007/s00520-015-2865-826265119)
Suzuki K, Yamanaka T, Hashimoto H, Shimada Y, Arata K, Matsui R, Goto K, Takiguchi T, Ohyanagi F, Kogure Y, Nogami N, Nakao M, Takeda K, Azuma K, Nagase S, Hayashi T, Fujiwara K, Shimada T, Seki N, Yamamoto N (2016) Randomized, double-blind, phase III trial of palonosetron versus granisetron in the triplet regimen for preventing chemotherapy-induced nausea and vomiting after highly emetogenic chemotherapy: TRIPLE study. Ann Oncol 27(8):1601–1606. https://doi.org/10.1093/annonc/mdw220. (PMID: 10.1093/annonc/mdw22027358385)
Tian W, Wang Z, Zhou J, Zhang S, Wang J, Chen Q, Huang C, Pan L, Zhang L, Huang J, Shen H, Lin T (2011) Randomized, double-blind, crossover study of palonosetron compared with granisetron for the prevention of chemotherapy-induced nausea and vomiting in a Chinese population. Med Oncol 28(1):71–78. https://doi.org/10.1007/s12032-009-9398-2. (PMID: 10.1007/s12032-009-9398-220049561)
Uchida M, Mori Y, Nakamura T, Kato K, Kamezaki K, Takenaka K, Shiratsuchi M, Kadoyama K, Miyamoto T, Akashi K (2017) Comparison between antiemetic effects of palonosetron and granisetron on chemotherapy-induced nausea and vomiting in Japanese patients treated with R-CHOP. Biol Pharm Bull 40(9):1499–1505. https://doi.org/10.1248/bpb.b17-00318. (PMID: 10.1248/bpb.b17-0031828867732)
Yu Z, Liu W, Wang L, Liang H, Huang Y, Si X, Zhang H, Liu D, Zhang H (2009) The efficacy and safety of palonosetron compared with granisetron in preventing highly emetogenic chemotherapy-induced vomiting in the Chinese cancer patients: a phase II, multicenter, randomized, double-blind, parallel, comparative clinical trial. Support Care Cancer 17(1):99–102. https://doi.org/10.1007/s00520-008-0503-4. (PMID: 10.1007/s00520-008-0503-418825421)
Ioannidis JP, Hesketh PJ, Lau J (2000) Contribution of dexamethasone to control of chemotherapy-induced nausea and vomiting: a meta-analysis of randomized evidence. J Clin Oncol 18(19):3409–3422. https://doi.org/10.1200/JCO.2000.18.19.3409. (PMID: 10.1200/JCO.2000.18.19.340911013282)
The Italian Multicenter Study Group (1999) A double-blind randomized study comparing intramuscular (i.m.) granisetron with i.m. granisetron plus dexamethasone in the prevention of delayed emesis induced by cisplatin. Anti-Cancer Drugs 10(5):465–470.
Heron JF, Goedhals L, Jordaan JP, Cunningham J, Cedar E (1994) Oral granisetron alone and in combination with dexamethasone: a double-blind randomized comparison against high-dose metoclopramide plus dexamethasone in prevention of cisplatin-induced emesis. The Granisetron Study Group Ann Oncol 5(7):579–574. https://doi.org/10.1093/oxfordjournals.annonc.a058927. (PMID: 10.1093/oxfordjournals.annonc.a058927)
Italian Group for Antiemetic R (1995) Dexamethasone, granisetron, or both for the prevention of nausea and vomiting during chemotherapy for cancer. N Engl J Med 332(1):1–5. https://doi.org/10.1056/NEJM199501053320101. (PMID: 10.1056/NEJM199501053320101)
Okada Y, Oba K, Furukawa N, Kosaka Y, Okita K, Yuki S, Komatsu Y, Celio L, Aapro M (2019) One-day versus three-day dexamethasone in combination with palonosetron for the prevention of chemotherapy-induced nausea and vomiting: a systematic review and individual patient data-based meta-analysis. Oncologist 24(12):1593–1600. https://doi.org/10.1634/theoncologist.2019-0133. (PMID: 10.1634/theoncologist.2019-0133312173436975929)
Massaro AM, Lenz KL (2005) Aprepitant: a novel antiemetic for chemotherapy-induced nausea and vomiting. Ann Pharmacother 39(1):77–85. https://doi.org/10.1345/aph.1E242. (PMID: 10.1345/aph.1E24215562136)
Jordan K, Warr DG, Hinke A, Sun L, Hesketh PJ (2016) Defining the efficacy of neurokinin-1 receptor antagonists in controlling chemotherapy-induced nausea and vomiting in different emetogenic settings-a meta-analysis. Support Care Cancer 24(5):1941–1954. https://doi.org/10.1007/s00520-015-2990-4. (PMID: 10.1007/s00520-015-2990-426476625)
Broder MS, Faria C, Powers A, Sunderji J, Cherepanov D (2014) The impact of 5-HT3RA use on cost and utilization in patients with chemotherapy-induced nausea and vomiting: systematic review of the literature. Am Health Drug Benefits 7(3):171–182. (PMID: 249914004070626)
Kashiwa M, Matsushita R (2019) Cost-utility analysis of palonosetron in the antiemetic regimen for cisplatin-containing highly emetogenic chemotherapy in Japan. BMC Health Serv Res 19(1):438. https://doi.org/10.1186/s12913-019-4281-0. (PMID: 10.1186/s12913-019-4281-0312622926604132)
Shimizu H, Suzuki K, Uchikura T, Tsuji D, Yamanaka T, Hashimoto H, Goto K, Matsui R, Seki N, Shimada T, Ikeda S, Ikegami N, Hama T, Yamamoto N, Sasaki T (2018) Economic analysis of palonosetron versus granisetron in the standard triplet regimen for preventing chemotherapy-induced nausea and vomiting in patients receiving highly emetogenic chemotherapy in Japan (TRIPLE phase III trial). J Pharm Health Care Sci 4:31. https://doi.org/10.1186/s40780-018-0128-9. (PMID: 10.1186/s40780-018-0128-9305557106287343)
Schünemann H, Brożek J, Guyatt G, Oxman A, editors (2013) GRADE handbook for grading quality of evidence and strength of recommendations. Updated October 2013. The GRADE Working Group. Available from guidelinedevelopment.org/handbook.

Keywords: Chemotherapy; Granisetron; Meta-analysis; Nausea; Palonosetron; Vomiting

0 (Antiemetics)
0 (Antineoplastic Agents)
0 (Serotonin 5-HT3 Receptor Antagonists)
5D06587D6R (Palonosetron)
WZG3J2MCOL (Granisetron)

Date Created: 20210516 Date Completed: 20220202 Latest Revision: 20220202

20231215

10.1007/s00228-021-03157-2

33993343