DOI QR코드

DOI QR Code

Efficacy and Safety of Neurokinin-1 Receptor Antagonists for Prevention of Chemotherapy-Induced Nausea and Vomiting: Systematic Review and Meta-analysis of Randomized Controlled Trials

  • Yuan, Dong-Mei (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Li, Qian (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Zhang, Qin (Department of Gynecology, Jinling Hospital, Nanjing University School of Medicine) ;
  • Xiao, Xin-Wu (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Yao, Yan-Wen (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Zhang, Yan (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Lv, Yan-Ling (Department of Respiratory Medicine, the Second Affiliated Hospital, Southeast University) ;
  • Liu, Hong-Bin (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Lv, Tang-Feng (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine) ;
  • Song, Yong (Department of Respiratory Medicine, Jinling Hospital, Nanjing University School of Medicine)
  • Published : 2016.06.01

Abstract

Objectives: Can addition of neurokinin-1 receptor antagonists (NK1-RAs) be considered as an ideal strategy for the prevention of chemotherapy-induced nausea and vomiting (CINV)? Researchers differ on this question. Materials and Methods: Electronic databases were searched for randomized control trials (RCTs) that evaluated the effectiveness and safety of NK1-RAs in preventing CINV. The primary end point was complete response (CR) in the acute, delayed, and overall phases after chemotherapy. Subgroup analyses evaluated the types of NK1-RAs, routines of administration, types of malignancies, regimens used in combination with NK1-RAs, and age of patients included in the studies. The incidences of different types of adverse events were also extracted to estimate the safety of NK1-RAs. Results: A total of 38 RCTs involving 13,923 patients were identified. The CR rate of patients receiving NK-RAs was significantly higher than patients in the control groups during overall phase (70.8% vs 56.0%, P<0.001), acute phase (85.1% vs 79.6%, P<0.001), and delayed phase (71.4% vs 58.2%, P<0.001). There were three studies including patients of children or adolescents, the CR rate was also significantly higher in the treatment group (overall phase: OR=2.807, P<0.001; acute phase: OR=2.863, P =0.012; delayed phase: OR=2.417, P<0.001). For all the other outcomes, patients in the NK1-RAs groups showed improvements compared to the control groups (incidence of nausea: 45.2% vs 45.9%, P<0.001; occurrence of vomiting: 22.6% vs 38.9%, P<0.001; usage of rescue drugs: 23.5% vs 34.1%, P<0.001). The pooled side effects from NK1-RAs did not significantly differ from previous reports and the toxicity rates in patients less than eighteen years old also did not diff between the two groups (P=0.497). However, we found that constipation and insomnia were more common in the patients of control groups, whereas diarrhea and hiccups were more frequently detected in patients receiving NK1-RAs. Conclusions: NK1-RAs improved the CR rate of CINV. They are effective for both adults and children. The use of NK1-RAs might be associated with the appearance of diarrhea and hiccups, while decreasing the possibility of constipation and insomnia.

Keywords

Neurokinin-1 receptor antagonist;chemotherapy-induced nausea and vomiting;aprepitant;meta-analysis

Acknowledgement

Supported by : National Science Foundation of Jiangsu Province of China, National Natural Science Foundation of China

References

  1. Roila F, Ruggeri B, Ballatori E, et al (2015). Aprepitant versus metoclopramide, both combined with dexamethasone, for the prevention of cisplatin-induced delayed emesis: a randomized, double-blind study. Ann Oncol, 26, 1248-53. https://doi.org/10.1093/annonc/mdv132
  2. Hesketh PJ (2008). Chemotherapy-induced nausea and vomiting. N Engl J Med, 358, 2482-94. https://doi.org/10.1056/NEJMra0706547
  3. Aapro M, Carides A, Rapoport BL, et al (2015). Aprepitant and fosaprepitant: a 10-year review of efficacy and safety. Oncologist, 20, 450-8. https://doi.org/10.1634/theoncologist.2014-0229
  4. Aapro M, Rugo H, Rossi G, et al (2014). A randomized phase III study evaluating the efficacy and safety of NEPA, a fixed-dose combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following moderately emetogenic chemotherapy. Ann Oncol, 25, 1328-33. https://doi.org/10.1093/annonc/mdu101
  5. Aapro MS, Molassiotis A, Olver I (2005). Anticipatory nausea and vomiting. Support Care Cancer, 13, 117-21. https://doi.org/10.1007/s00520-004-0745-8
  6. Aksu G, Dolasik I, Ensaroglu F, et al (2013). Evaluation of the efficacy of aprepitant on the prevention of chemotherapyinduced nausea and vomiting and quality of life with functional living index emesis. Balkan Med J, 30, 64-7. https://doi.org/10.5152/balkanmedj.2012.087
  7. Albany C, Brames MJ, Fausel C, et al (2012). Randomized, double-blind, placebo-controlled, phase III cross-over study evaluating the oral neurokinin-1 antagonist aprepitant in combination with a 5HT3 receptor antagonist and dexamethasone in patients with germ cell tumors receiving 5-day cisplatin combination chemotherapy regimens: a hoosier oncology group study. J Clin Oncol, 30, 3998-4003. https://doi.org/10.1200/JCO.2011.39.5558
  8. Altman DG, Bland JM (1997). Statistics notes. Units of analysis. Bmj, 314, 1874. https://doi.org/10.1136/bmj.314.7098.1874
  9. Arpornwirat W, Albert I, Hansen VL, et al (2009). Phase 2 trial results with the novel neurokinin-1 receptor antagonist casopitant in combination with ondansetron and dexamethasone for the prevention of chemotherapy-induced nausea and vomiting in cancer patients receiving moderately emetogenic chemotherapy. Cancer, 115, 5807-16. https://doi.org/10.1002/cncr.24630
  10. Badar T, Cortes J, Borthakur G, et al (2015). Phase II, open label, randomized comparative trial of ondansetron alone versus the combination of ondansetron and aprepitant for the prevention of nausea and vomiting in patients with hematologic malignancies receiving regimens containing high-dose cytarabine. Biomed Res Int, 2015, 497597.
  11. Bakhshi S, Batra A, Biswas B, et al (2015). Aprepitant as an add-on therapy in children receiving highly emetogenic chemotherapy: a randomized, double-blind, placebocontrolled trial. Support Care Cancer, 23, 3229-37. https://doi.org/10.1007/s00520-015-2714-9
  12. Basch E, Prestrud AA, Hesketh PJ, et al (2011). Antiemetics: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol, 29, 4189-98. https://doi.org/10.1200/JCO.2010.34.4614
  13. Bloechl-Daum B, Deuson RR, Mavros P, et al (2006). Delayed nausea and vomiting continue to reduce patients’ quality of life after highly and moderately emetogenic chemotherapy despite antiemetic treatment. J Clin Oncol, 24, 4472-8. https://doi.org/10.1200/JCO.2006.05.6382
  14. Campos D, Pereira JR, Reinhardt RR, et al (2001). Prevention of cisplatin-induced emesis by the oral neurokinin-1 antagonist, MK-869, in combination with granisetron and dexamethasone or with dexamethasone alone. J Clin Oncol, 19, 1759-67. https://doi.org/10.1200/JCO.2001.19.6.1759
  15. Chawla SP, Grunberg SM, Gralla RJ, et al (2003). Establishing the dose of the oral NK1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting. Cancer, 97, 2290-300. https://doi.org/10.1002/cncr.11320
  16. Cocquyt V, Van Belle S, Reinhardt RR, et al (2001). Comparison of L-758,298, a prodrug for the selective neurokinin-1 antagonist, L-754,030, with ondansetron for the prevention of cisplatin-induced emesis. Eur J Cancer, 37, 835-42. https://doi.org/10.1016/S0959-8049(00)00416-0
  17. de Wit R, Herrstedt J, Rapoport B, et al (2004). The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials. Eur J Cancer, 40, 403-10.
  18. DerSimonian R, Laird N (1986). Meta-analysis in clinical trials. Control Clin Trials, 7, 177-88. https://doi.org/10.1016/0197-2456(86)90046-2
  19. Di Maio M, Bria E, Banna GL, et al (2013). Prevention of chemotherapy-induced nausea and vomiting and the role of neurokinin 1 inhibitors: from guidelines to clinical practice in solid tumors. Anticancer Drugs, 24, 99-111. https://doi.org/10.1097/CAD.0b013e328359d7ba
  20. dos Santos LV, Souza FH, Brunetto AT, et al (2012). Neurokinin-1 receptor antagonists for chemotherapy-induced nausea and vomiting: a systematic review. J Natl Cancer Inst, 104, 1280-92. https://doi.org/10.1093/jnci/djs335
  21. Duval S, Tweedie R (2000). Trim and fill: A simple funnel-plotbased method of testing and adjusting for publication bias in meta-analysis. Biometrics, 56, 455-63. https://doi.org/10.1111/j.0006-341X.2000.00455.x
  22. Gore L, Chawla S, Petrilli A, et al (2009). Aprepitant in adolescent patients for prevention of chemotherapy-induced nausea and vomiting: a randomized, double-blind, placebocontrolled study of efficacy and tolerability. Pediatr Blood Cancer, 52, 242-7. https://doi.org/10.1002/pbc.21811
  23. Grunberg SM (2007). Antiemetic activity of corticosteroids in patients receiving cancer chemotherapy: dosing, efficacy, and tolerability analysis. Ann Oncol, 18, 233-40.
  24. Grunberg SM, Deuson RR, Mavros P, et al (2004). Incidence of chemotherapy-induced nausea and emesis after modern antiemetics. Cancer, 100, 2261-8. https://doi.org/10.1002/cncr.20230
  25. Grunberg SM, Rolski J, Strausz J, et al (2009). Efficacy and safety of casopitant mesylate, a neurokinin 1 (NK1)-receptor antagonist, in prevention of chemotherapy-induced nausea and vomiting in patients receiving cisplatin-based highly emetogenic chemotherapy: a randomised, double-blind, placebo-controlled trial. Lancet Oncol, 10, 549-58. https://doi.org/10.1016/S1470-2045(09)70109-3
  26. Herrington JD, Jaskiewicz AD, Song J (2008). Randomized, placebo-controlled, pilot study evaluating aprepitant single dose plus palonosetron and dexamethasone for the prevention of acute and delayed chemotherapy-induced nausea and vomiting. Cancer, 112, 2080-7. https://doi.org/10.1002/cncr.23364
  27. Herrstedt J, Apornwirat W, Shaharyar A, et al (2009). Phase III trial of casopitant, a novel neurokinin-1 receptor antagonist, for the prevention of nausea and vomiting in patients receiving moderately emetogenic chemotherapy. J Clin Oncol, 27, 5363-9. https://doi.org/10.1200/JCO.2009.21.8511
  28. Herrstedt J, Roila F (2009). Chemotherapy-induced nausea and vomiting: ESMO clinical recommendations for prophylaxis. Ann Oncol, 4, 156-8.
  29. Hesketh PJ, Gralla RJ, Webb RT, et al (1999). Randomized phase II study of the neurokinin 1 receptor antagonist CJ-11,974 in the control of cisplatin-induced emesis. J Clin Oncol, 17, 338-43. https://doi.org/10.1200/JCO.1999.17.1.338
  30. Hesketh PJ, Grunberg SM, Gralla RJ, et al (2003). The oral neurokinin-1 antagonist aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a multinational, randomized, double-blind, placebo-controlled trial in patients receiving high-dose cisplatin--the Aprepitant Protocol 052 Study Group. J Clin Oncol, 21, 4112-9. https://doi.org/10.1200/JCO.2003.01.095
  31. Hesketh PJ, Rossi G, Rizzi G, et al (2014). Efficacy and safety of NEPA, an oral combination of netupitant and palonosetron, for prevention of chemotherapy-induced nausea and vomiting following highly emetogenic chemotherapy: a randomized dose-ranging pivotal study. Ann Oncol, 25, 1340-6. https://doi.org/10.1093/annonc/mdu110
  32. Higgins JP, Thompson SG (2002). Quantifying heterogeneity in a meta-analysis. Stat Med, 21, 1539-58. https://doi.org/10.1002/sim.1186
  33. Hu Z, Cheng Y, Zhang H, et al (2014). Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized, double-blind, placebo-controlled phase III trial. Support Care Cancer, 22, 979-87. https://doi.org/10.1007/s00520-013-2043-9
  34. Ito Y, Karayama M, Inui N, et al (2014). Aprepitant in patients with advanced non-small-cell lung cancer receiving carboplatin-based chemotherapy. Lung Cancer, 84, 259-64. https://doi.org/10.1016/j.lungcan.2014.03.017
  35. Jordan K, Gralla R, Jahn F, et al (2014). International antiemetic guidelines on chemotherapy induced nausea and vomiting (CINV): content and implementation in daily routine practice. Eur J Pharmacol, 722, 197-202. https://doi.org/10.1016/j.ejphar.2013.09.073
  36. Kang HJ, Loftus S, Taylor A, et al (2015). Aprepitant for the prevention of chemotherapy-induced nausea and vomiting in children: a randomised, double-blind, phase 3 trial. Lancet Oncol, 16, 385-94. https://doi.org/10.1016/S1470-2045(15)70061-6
  37. Kitayama H, Tsuji Y, Sugiyama J, et al (2015). Efficacy of palonosetron and 1-day dexamethasone in moderately emetogenic chemotherapy compared with fosaprepitant, granisetron, and dexamethasone: a prospective randomized crossover study. Int J Clin Oncol, 20, 1051-6. https://doi.org/10.1007/s10147-015-0823-6
  38. Lasseter KC, Gambale J, Jin B, et al (2007). Tolerability of fosaprepitant and bioequivalency to aprepitant in healthy subjects. J Clin Pharmacol, 47, 834-40. https://doi.org/10.1177/0091270007301800
  39. Liaw CC, Wang CH, Chang HK, et al (2001). Gender discrepancy observed between chemotherapy-induced emesis and hiccups. Support Care Cancer, 9, 435-41. https://doi.org/10.1007/s005200000231
  40. Martin AR, Pearson JD, Cai B, et al (2003a). Assessing the impact of chemotherapy-induced nausea and vomiting on patients' daily lives: a modified version of the Functional Living Index-Emesis (FLIE) with 5-day recall. Support Care Cancer, 11, 522-7. https://doi.org/10.1007/s00520-003-0482-4
  41. Martin CG, Rubenstein EB, Elting LS, et al (2003b). Measuring chemotherapy-induced nausea and emesis. Cancer, 98, 645-55. https://doi.org/10.1002/cncr.11540
  42. Munoz M, Covenas R (2013). Safety of neurokinin-1 receptor antagonists. Expert Opin Drug Saf, 12, 673-85. https://doi.org/10.1517/14740338.2013.804059
  43. Nasu R, Nannya Y, Kurokawa M (2015). A randomized controlled study evaluating the efficacy of aprepitant for highly/moderately emetogenic chemotherapies in hematological malignancies. Int J Hematol, 101, 376-85. https://doi.org/10.1007/s12185-015-1735-y
  44. Navari RM (2007). Fosaprepitant (MK-0517): a neurokinin-1 receptor antagonist for the prevention of chemotherapyinduced nausea and vomiting. Expert Opin Investig Drugs, 16, 1977-85. https://doi.org/10.1517/13543784.16.12.1977
  45. Navari RM, Gray SE, Kerr AC (2011). Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: a randomized phase III trial. J Support Oncol, 9, 188-95. https://doi.org/10.1016/j.suponc.2011.05.002
  46. Navari RM, Reinhardt RR, Gralla RJ, et al (1999). Reduction of cisplatin-induced emesis by a selective neurokinin-1- receptor antagonist. L-754,030 Antiemetic Trials Group. N Engl J Med, 340, 190-5. https://doi.org/10.1056/NEJM199901213400304
  47. Poli-Bigelli S, Rodrigues-Pereira J, Carides AD, et al (2003). Addition of the neurokinin 1 receptor antagonist aprepitant to standard antiemetic therapy improves control of chemotherapy-induced nausea and vomiting. Results from a randomized, double-blind, placebo-controlled trial in Latin America. Cancer, 97, 3090-8. https://doi.org/10.1002/cncr.11433
  48. Rapoport BL, Jordan K, Boice JA, et al (2010). Aprepitant for the prevention of chemotherapy-induced nausea and vomiting associated with a broad range of moderately emetogenic chemotherapies and tumor types: a randomized, double-blind study. Support Care Cancer, 18, 423-31. https://doi.org/10.1007/s00520-009-0680-9
  49. Roila F, Rolski J, Ramlau R, et al (2009). Randomized, double-blind, dose-ranging trial of the oral neurokinin-1 receptor antagonist casopitant mesylate for the prevention of cisplatin-induced nausea and vomiting. Ann Oncol, 20, 1867-73. https://doi.org/10.1093/annonc/mdp194
  50. Roila F, Ruggeri B, Ballatori E, et al (2014). Aprepitant versus dexamethasone for preventing chemotherapy-induced delayed emesis in patients with breast cancer: a randomized double-blind study. J Clin Oncol, 32, 101-6.
  51. Saito H, Yoshizawa H, Yoshimori K, et al (2013). Efficacy and safety of single-dose fosaprepitant in the prevention of chemotherapy-induced nausea and vomiting in patients receiving high-dose cisplatin: a multicentre, randomised, double-blind, placebo-controlled phase 3 trial. Ann Oncol, 24, 1067-73. https://doi.org/10.1093/annonc/mds541
  52. Saito M, Aogi K, Sekine I, 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, 115-24. https://doi.org/10.1016/S1470-2045(08)70313-9
  53. Schmitt T, Goldschmidt H, Neben K, et al (2014). Aprepitant, granisetron, and dexamethasone for prevention of chemotherapy-induced nausea and vomiting after highdose melphalan in autologous transplantation for multiple myeloma: results of a randomized, placebo-controlled phase III trial. J Clin Oncol, 32, 3413-20. https://doi.org/10.1200/JCO.2013.55.0095
  54. Schmoll HJ, Aapro MS, Poli-Bigelli S, et al (2006). Comparison of an aprepitant regimen with a multiple-day ondansetron regimen, both with dexamethasone, for antiemetic efficacy in high-dose cisplatin treatment. Ann Oncol, 17, 1000-6. https://doi.org/10.1093/annonc/mdl019
  55. Shillingburg A, Biondo L (2014). Aprepitant and fosaprepitant use in children and adolescents at an academic medical center. J Pediatr Pharmacol Ther, 19, 127-31.
  56. Stiff PJ, Fox-Geiman MP, Kiley K, et al (2013). Prevention of nausea and vomiting associated with stem cell transplant: results of a prospective, randomized trial of aprepitant used with highly emetogenic preparative regimens. Biol Blood Marrow Transplant, 19, 49-55. https://doi.org/10.1016/j.bbmt.2012.07.019
  57. Takahashi T, Hoshi E, Takagi M, et al (2010). Multicenter, phase II, placebo-controlled, double-blind, randomized study of aprepitant in Japanese patients receiving high-dose cisplatin. Cancer Sci, 101, 2455-61. https://doi.org/10.1111/j.1349-7006.2010.01689.x
  58. Tanioka M, Kitao A, Matsumoto K, et al (2013). A randomised, placebo-controlled, double-blind study of aprepitant in nondrinking women younger than 70 years receiving moderately emetogenic chemotherapy. Br J Cancer, 109, 859-65. https://doi.org/10.1038/bjc.2013.400
  59. Tattersall FD, Rycroft W, Francis B, et al (1996). Tachykinin NK1 receptor antagonists act centrally to inhibit emesis induced by the chemotherapeutic agent cisplatin in ferrets. Neuropharmacol, 35, 1121-9. https://doi.org/10.1016/S0028-3908(96)00020-2
  60. Van Belle S, Lichinitser MR, Navari RM, et al (2002). Prevention of cisplatin-induced acute and delayed emesis by the selective neurokinin-1 antagonists, L-758,298 and MK-869. Cancer, 94, 3032-41. https://doi.org/10.1002/cncr.10516
  61. Wadler S, Benson AB, 3rd, Engelking C, et al (1998). Recommended guidelines for the treatment of chemotherapyinduced diarrhea. J Clin Oncol, 16, 3169-78. https://doi.org/10.1200/JCO.1998.16.9.3169
  62. Warr DG, Grunberg SM, Gralla RJ, et al (2005a). The oral NK(1) antagonist aprepitant for the prevention of acute and delayed chemotherapy-induced nausea and vomiting: Pooled data from 2 randomised, double-blind, placebo controlled trials. Eur J Cancer, 41, 1278-85. https://doi.org/10.1016/j.ejca.2005.01.024
  63. Warr DG, Hesketh PJ, Gralla RJ, et al (2005b). Efficacy and tolerability of aprepitant for the prevention of chemotherapyinduced nausea and vomiting in patients with breast cancer after moderately emetogenic chemotherapy. J Clin Oncol, 23, 2822-30. https://doi.org/10.1200/JCO.2005.09.050
  64. Yeo W, Mo FK, Suen JJ, et al (2009). A randomized study of aprepitant, ondansetron and dexamethasone for chemotherapy-induced nausea and vomiting in Chinese breast cancer patients receiving moderately emetogenic chemotherapy. Breast Cancer Res Treat, 113, 529-35. https://doi.org/10.1007/s10549-008-9957-9

Cited by

  1. HTX-019: polysorbate 80- and synthetic surfactant-free neurokinin 1 receptor antagonist for chemotherapy-induced nausea and vomiting prophylaxis pp.1744-8301, 2018, https://doi.org/10.2217/fon-2018-0577
  2. Effect of Antiemetic Agents on Hiccups during Chemotherapy in Patients with Lung Cancer vol.09, pp.04, 2018, https://doi.org/10.4236/pp.2018.94010