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Granisetron Extended-Release Injection: A Review in Chemotherapy-Induced Nausea and Vomiting

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Abstract

An extended-release (ER) subcutaneously injectable formulation of the first-generation 5-HT3 receptor antagonist granisetron is now available in the USA (Sustol®), where it is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide combination chemotherapy regimens in adults. Granisetron ER is administered as a single subcutaneous injection and uses an erosion-controlled drug-delivery system to allow prolonged granisetron release. Primary endpoint data from phase III studies after an initial cycle of chemotherapy indicate that, when used as part of an antiemetic regimen, granisetron ER injection is more effective than intravenous ondansetron in preventing delayed CINV following highly emetogenic chemotherapy (HEC); is noninferior to intravenous palonosetron in preventing both acute CINV following MEC or HEC and delayed CINV following MEC; and is similar, but not superior, to palonosetron in preventing delayed CINV following HEC. The benefits of granisetron ER were seen in various patient subgroups, including those receiving anthracycline plus cyclophosphamide-based HEC, and (in an extension of one of the studies) over multiple MEC or HEC cycles. Granisetron ER injection is generally well tolerated, with an adverse event profile similar to that of ondansetron or palonosetron. Thus, granisetron ER injection expands the options for preventing both acute and delayed CINV in adults with cancer receiving MEC or anthracycline plus cyclophosphamide-based HEC.

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References

  1. Navari RM, Aapro M. Antiemetic prophylaxis for chemotherapy-induced nausea and vomiting. N Engl J Med. 2016;374(14):1356–67.

    Article  CAS  PubMed  Google Scholar 

  2. Nasir SS, Schwartberg LS. Recent advances in preventing chemotherapy-induced nausea and vomiting. 2016. http://www.cancernetwork.com. Accessed 9 Nov 2016.

  3. National Comprehensive Cancer Network®. NCCN clinical practice guidelines in oncology (NCCN Guidelines®): antiemesis, version 2.2016. 2016. http://www.NCCN.org. Accessed 9 Nov 2016.

  4. Basch E, Prestrud AA, Hesketh PJ, et al. Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol. 2011;29(31):4189–98.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Hesketh PJ, Bohlke K, Lyman GH, et al. Antiemetics: American Society of Clinical Oncology focused guideline update. J Clin Oncol. 2016;34(4):381–6.

    Article  PubMed  Google Scholar 

  6. Shankar A, Roy S, Malik A, et al. Prevention of chemotherapy-induced nausea and vomiting in cancer patients. Asian Pac J Cancer Prev. 2015;16(15):6207–13.

    Article  PubMed  Google Scholar 

  7. Schwartzberg LS, Rugo HS, Aapro MS. New and emerging therapeutic options for the management of chemotherapy-induced nausea and vomiting. Clin Adv Hematol Oncol. 2015;13(3 Suppl 3):3–13.

    PubMed  Google Scholar 

  8. Duggan ST, Curran MP. Transdermal granisetron. Drugs. 2009;69(18):2597–605.

    Article  CAS  PubMed  Google Scholar 

  9. Heron Therapeutics Inc. Sustol® (granisetron) extended-release injection, for subcutaneous use: US prescribing information. 2016. http://www.fda.gov. Accessed 9 Nov 2016.

  10. Heller J, Barr J. Biochronomer technology. Expert Opin Drug Deliv. 2005;2(1):169–83.

    Article  CAS  PubMed  Google Scholar 

  11. Ottoboni T, Gelder MS, O’Boyle E. Biochronomer technology™ and the development of APF530, a sustained release formulation of granisetron. J Exp Pharmacol. 2014;6:15–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Brygger L, Herrstedt J. 5-Hydroxytryptamine3 receptor antagonists and cardiac side effects. Expert Opin Drug Saf. 2014;13(10):1407–22.

    Article  CAS  PubMed  Google Scholar 

  13. Mason JW, Moon TE, O’Boyle E, et al. A randomized, placebo-controlled, four-period crossover, definitive QT study of the effects of APF530 exposure, high-dose intravenous granisetron, and moxifloxacin on QTc prolongation. Cancer Manag Res. 2014;6:181–90.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Smith JA, Julius JM, Gaikwad A, et al. Evaluating the potential effect on fetal tissue after exposure to granisetron during pregnancy. Reprod Toxicol. 2015;53:92–8.

    Article  CAS  PubMed  Google Scholar 

  15. Gabrail N, Yanagihara R, Spaczynski M, et al. Pharmacokinetics, safety, and efficacy of APF530 (extended-release granisetron) in patients receiving moderately or highly emetogenic chemotherapy: results of two phase II trials. Cancer Manag Res. 2015;7:83–92.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Morrison D, Anderson A, Slama M, et al. Phase 1 bioavailability study comparing 2 different subcutaneous routes of administration for APF530 [abstract no. 11-16-P]. Support Care Cancer. 2015;23(Suppl 1):S132.

    Google Scholar 

  17. Raftopoulos H, Cooper W, O’Boyle E, et al. 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. 2015;23(3):723–32.

    Article  PubMed  Google Scholar 

  18. Schnadig ID, Agajanian R, Dakhil C, et al. APF530 (granisetron injection extended-release) in a three-drug regimen for delayed CINV in highly emetogenic chemotherapy. Future Oncol. 2016;12(12):1469–81.

    Article  CAS  PubMed  Google Scholar 

  19. Schnadig I, Braun E, Mosier M, et al. Effect of APF530 on health-related quality of life (QOL) and other chemotherapy-induced nausea and vomiting (CINV) end points: phase III MAGIC trial [abstract]. J Clin Oncol. 2016;34(Suppl):e21666.

    Google Scholar 

  20. Schwartzberg LS, Gabrail NY, Hrom JS, et al. Phase III MAGIC trial of APF530 v ondansetron (Ond) with fosaprepitant (Fos) + dexamethasone (Dex) for highly emetogenic chemotherapy (HEC)-induced nausea and vomiting: analysis by age and gender [abstract no. e21700]. J Clin Oncol. 2016;34(Suppl).

  21. Schnadig I, Agajanian R, Dakhil S, et al. Phase 3 comparison of APF530 versus ondansetron, each in a guideline-recommended 3-drug regimen for prevention of chemotherapy-induced nausea and vomiting due to anthracycline + cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC) regimens: a post hoc subgroup analysis of the MAGIC trial [abstract no. P1-10-07]. In: San Antonio Breast Cancer Symposium; 2015.

  22. Raftopoulos H, Boccia R, Cooper W, et al. Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: analysis by American Society of Clinical Oncology emetogenicity criteria. Future Oncol. 2015;11(18):2541–51.

    Article  CAS  PubMed  Google Scholar 

  23. Boccia R, Cooper W, O’Boyle E. Sustained antiemetic responses with APF530 (sustained-release granisetron) during multiple cycles of emetogenic chemotherapy. J Community Support Oncol. 2015;13(2):38–46.

    Article  PubMed  Google Scholar 

  24. Boccia R, O’Boyle E, Cooper W. Randomized phase III trial of APF530 versus palonosetron in the prevention of chemotherapy-induced nausea and vomiting in a subset of patients with breast cancer receiving moderately or highly emetogenic chemotherapy. BMC Cancer. 2016;16:166.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Jordan K, Jahn F, Aapro M. Recent developments in the prevention of chemotherapy-induced nausea and vomiting (CINV): a comprehensive review. Ann Oncol. 2015;26(6):1081–90.

    Article  CAS  PubMed  Google Scholar 

  26. Eisai. Aloxi® (palonosetron HCl) injection for intravenous use: US prescribing information. 2016. http://www.fda.gov. Accessed 9 Nov 2016.

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Acknowledgements

During the peer review process, the manufacturer of granisetron ER was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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  1. Springer, Private Bag 65901, Mairangi Bay, 0754, Auckland, New Zealand

    Emma D. Deeks

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  1. Emma D. Deeks
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Correspondence to Emma D. Deeks.

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The preparation of this review was not supported by any external funding.

Conflicts of interest

Emma Deeks is a salaried employee of Adis/Springer, is responsible for the article content and declares no relevant conflicts of interest.

Additional information

The manuscript was reviewed by: V. Lorusso, Medical Oncology Unit, National Cancer Institute Giovanni Paolo II, Bari, Italy; R. M. Navari, Division of Hematology Oncology, University of Alabama Birmingham School of Medicine, Birmingham, AL, USA.

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Deeks, E.D. Granisetron Extended-Release Injection: A Review in Chemotherapy-Induced Nausea and Vomiting. Drugs 76, 1779–1786 (2016). https://doi.org/10.1007/s40265-016-0664-2

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