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Indian Journal of Medical and Paediatric Oncology
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DRUG REVIEW
Year : 2019  |  Volume : 40  |  Issue : 2  |  Page : 274-276  

Olanzapine: The game-changer “antiemetic”


Department of Medical Oncology, Cancer Institute (WIA), Chennai, Tamil Nadu, India

Date of Web Publication17-Oct-2019

Correspondence Address:
Manikandan Dhanushkodi
Department of Medical Oncology, Cancer Institute (WIA), 38 Sardar Patel Road, Chennai - 600 036, Tamil Nadu
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ijmpo.ijmpo_151_19

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  Abstract 


Chemotherapy-induced nausea and vomiting (CINV) is significantly debilitating and worsens the quality of life. Olanzapine, an atypical antipsychotic drug, also has an antiemetic potential. Studies have shown that olanzapine-based regimens have similar efficacy as compared to aprepitant in patients receiving highly emetogenic chemotherapy (HEC). National Comprehensive Cancer Network guidelines also recommends olanzapine-based regimen in HEC. Olanzapine, palonosetron, dexamethasone regimen is a cost-effective option in resource-limited settings in patients receiving HEC.

Keywords: Chemotherapy-induced nausea and vomiting, highly emetogenic chemotherapy, olanzapine


How to cite this article:
Dhanushkodi M. Olanzapine: The game-changer “antiemetic”. Indian J Med Paediatr Oncol 2019;40:274-6

How to cite this URL:
Dhanushkodi M. Olanzapine: The game-changer “antiemetic”. Indian J Med Paediatr Oncol [serial online] 2019 [cited 2019 Nov 12];40:274-6. Available from: http://www.ijmpo.org/text.asp?2019/40/2/274/269442


  Introduction Top


Chemotherapy-induced nausea and vomiting (CINV) is debilitating and worsens the quality of life. Acute CINV occurs within 24 h of chemotherapy, and delayed CINV is predominant during 24–48 h until 5 days. The prevention strategies for highly emetogenic chemotherapy (HEC) include corticosteroids, serotonin (5-HT3) receptor antagonists, and neurokinin 1 receptor antagonists. Olanzapine is an antipsychotic drug of thiobenzodiazepine class that is used in the management of schizophrenia and bipolar disorder. This drug has also shown to have high antiemetic potential.


  Mechanism Of Action Top


Olanzapine acts as an antagonist on multiple receptors including dopaminergic (D1, D2, D3, and D4), serotonergic (5-HT2A, 5-HT2C, 5-HT3, and 5-HT6), adrenergic (alpha 1), histaminic (H1), and muscarinic (M1, M2, M3, and M4) receptors.


  Discovery Top


In 1954, chlorpromazine was shown to be effective in controlling CINV in patients with advanced cancer.[1] Subsequently, in 1960, preclinical studies proved that haloperidol has antiemetic properties.[2] In 1992, Fuller and Snoddy showed that, in rats, olanzapine blocks serotonin and dopamine receptors better than clozapine and could be a potential antipsychotic drug.[3] It was termed novel “atypical” antipsychotic as it has additional anticholinergic properties that have lesser extrapyramidal symptoms.[4] In 1995, olanzapine showed efficacy in patient with schizophrenia with lower incidence of extrapyramidal symptoms.[5] In 2000, a case report highlighting the antiemetic properties of olanzapine was published.[6] This lead to the development of various clinical trials with olanzapine.


  Approval Top


It is United States Food and Drug Act approved in the management of schizophrenia and bipolar disorder. Olanzapine is approved by the Drugs Controller General of India for the treatment of schizophrenia and resistant depression. It is currently not approved for use as antiemetic.


  Highly Emetogenic Chemotherapy Top


The National Comprehensive Cancer Network (NCCN) defined HEC (>90% risk of emesis): cisplatin, carboplatin ≥AUC 4, adriamycin-cyclophosphamide (AC), cyclophosphamide >1500 mg/m 2, ifosfamide >2 g/m 2 per dose, adriamycin >60 mg/m 2, epirubicin >90 mg/m 2, and dacarbazine.


  Olanzapine Dose Top


  • Tablet olanzapine 10 mg D1, D2, D3, and D4.



  Olanzapine, Palonosetron, Dexamethasone Regimen Top


  • Tablet olanzapine 10 mg D1–D4
  • Injection palonosetron 0.25 mg D1
  • Injection dexamethasone 12 mg intravenous D1.



  Why Olanzapine-Based Regimen is Better That Other Regimens? Top


Navari et al. showed that olanzapine, palonosetron, dexamethasone (OPD) regimen has similar control over nausea and vomiting as compared to aprepitant, palonosetron, dexamethasone (APD) regimen in patients receiving HEC. The second study showed that regimen olanzapine, APD (OAPD) had a superior efficacy as compared to APD regimen.[7] A prospective study also demonstrated that APD regimen was as effective as OPD for patients with breast cancer who received AC chemotherapy.[8] [Table 1] In a recent study, olanzapine proved to be effective in patients who failed aprepitant-based regimen while receiving HEC.[9] Mini OPD regimen (tablet olanzapine 5 mg D1 and D2 along with palonosetron and dexamethasone) has shown to be cost-effective in patients receiving weekly cisplatin for carcinoma cervix.[10] Addition of olanzapine to palonosetron and dexamethasone significantly reduces nausea and the need for rescue medications in patients receiving moderately emetogenic chemotherapy.[11] A meta-analysis revealed that olanzapine is more effective than other antiemetics for controlling CINV in delayed and overall phase and 5 mg is equally as effective as 10 mg dose.[12] A systematic review and meta-analysis from Japan revealed that olanzapine, when substituted instead of aprepitant in the APD regimen, can be hugely cost-effective.[13] Although the newer antiemetics (fosaprepitant,[14] netupitant,[15] and rolapitant [16]) have shown to be effective in HEC, they are less effective in controlling nausea and are more expensive.
Table 1: Phase 3 trials comparing olanzapine versus other antiemetic regimen in patients receiving highly emetogenic chemotherapy

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  Guidelines Top


  • The NCCN 2019 antiemetic guidelines recommends OPD regimen for the treatment of HEC
  • The ASCO 2018 antiemetic guidelines recommends addition of olanzapine to antiemetic regimen in patients receiving HEC
  • The Multinational Association of Supportive Care in Cancer/European Society of Medical Oncology 2016 antiemetic guidelines recommends OPD as an effective antiemetic regimen.


Toxicity

The side effect of olanzapine is sedation (severe in 5%[7]). If patients experience sedation, the dose can be reduced to 5 mg/day.


  Olanzapine, Palonosetron, Dexamethasone Failure Top


Patients who have breakthrough emesis while on olanzapine can be treated with aprepitant-based regimen.


  Cost-Effectiveness Top


Olanzapine (6 cycles, Rs. 170/-) is priced 50 times lower as compared to aprepitant (6 cycles, Rs. 9000/-). A recent study from Southeast Asia showed olanzapine-based regimen to be very cost-effective.[19]


  Conclusion Top


OPD regimen should be the preferred antiemetic schedule for all patients receiving HEC as it has similar efficacy with minimal toxicity as compared to APD regimen. The NCCN 2019 antiemetic guidelines recommends OPD regimen for HEC. Further considering the low cost of therapy, it is an attractive, cost-effective option in a resource-limited setting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Homburger F, Smithy G. Chlorpromazine in patients with nausea and vomiting due to advanced cancer. N Engl J Med 1954;251:820-2.  Back to cited text no. 1
    
2.
Janssen PA, Niemegeers CJ, Schellekens KH. Chemistry and pharmacology of compounds related to 4-(4-hydroxy-4-phenyl-piperidino)-butyrophenone. III. Duration of antiemetic action and oral effectiveness of haloperidol (R 1625) and of chlorpromazine in dogs. Arzneimittelforschung 1960;10:955.  Back to cited text no. 2
    
3.
Fuller RW, Snoddy HD. Neuroendocrine evidence for antagonism of serotonin and dopamine receptors by olanzapine (LY170053), an antipsychotic drug candidate. Res Commun Chem Pathol Pharmacol 1992;77:87-93.  Back to cited text no. 3
    
4.
Moore NA, Tye NC, Axton MS, Risius FC. The behavioral pharmacology of olanzapine, a novel “atypical” antipsychotic agent. J Pharmacol Exp Ther 1992;262:545-51.  Back to cited text no. 4
    
5.
Baldwin DS, Montgomery SA. First clinical experience with olanzapine (LY 170053): Results of an open-label safety and dose-ranging study in patients with schizophrenia. Int Clin Psychopharmacol 1995;10:239-44.  Back to cited text no. 5
    
6.
Pirl WF, Roth AJ. Remission of chemotherapy-induced emesis with concurrent olanzapine treatment: A case report. Psychooncology 2000;9:84-7.  Back to cited text no. 6
    
7.
Navari RM, Qin R, Ruddy KJ, Liu H, Powell SF, Bajaj M, et al. Olanzapine for the prevention of chemotherapy-induced nausea and vomiting. N Engl J Med 2016;375:134-42.  Back to cited text no. 7
    
8.
Shivaprakash G, Udupa KS, Sarayu V, Thomas J, Gupta V, Pallavi LC, et al. Olanzapine versus aprepitant for the prophylaxis of chemotherapy-induced nausea and vomiting in breast cancer patients receiving doxorubicin-cyclophosphamide regimen: A prospective, nonrandomized, open-label study. Indian J Pharmacol 2017;49:451-7.  Back to cited text no. 8
[PUBMED]  [Full text]  
9.
Mehra N, Ganesan P, Ganesan TS, Veeriah S, Boopathy A, Radhakrishnan V, et al. Effectiveness of olanzapine in patients who fail therapy with aprepitant while receiving highly emetogenic chemotherapy. Med Oncol 2017;35:12.  Back to cited text no. 9
    
10.
Mehra N, Ganesan P, Dhanushkodi M, Ganesan TS, Radhakrishnan V, Jayachandran PK, et al. An effective anti-emetic regimen for less than $2 USD: A prospective observational study. J Clin Oncol 2018;36:e22194-4.  Back to cited text no. 10
    
11.
Jeon SY, Han HS, Bae WK, Park MR, Shim H, Lee SC, et al. A randomized, double-blind, placebo-controlled study of the safety and efficacy of olanzapine for the prevention of chemotherapy-induced nausea and vomiting in patients receiving moderately emetogenic chemotherapy: Results of the Korean South West Oncology Group (KSWOG) study. Cancer Res Treat 2019;51:90-7.  Back to cited text no. 11
    
12.
Yang T, Liu Q, Lu M, Ma L, Zhou Y, Cui Y, et al. Efficacy of olanzapine for the prophylaxis of chemotherapy-induced nausea and vomiting: A meta-analysis. Br J Clin Pharmacol 2017;83:1369-79.  Back to cited text no. 12
    
13.
Yokoe T, Hayashida T, Nagayama A, Nakashoji A, Maeda H, Seki T, et al. Effectiveness of antiemetic regimens for highly emetogenic chemotherapy-induced nausea and vomiting: A systematic review and network meta-analysis. Oncologist 2019;24:e347-57.  Back to cited text no. 13
    
14.
Ruhlmann CH, Christensen TB, Dohn LH, Paludan M, Rønnengart E, Halekoh U, et al. Efficacy and safety of fosaprepitant for the prevention of nausea and emesis during 5 weeks of chemoradiotherapy for cervical cancer (the GAND-emesis study): A multinational, randomised, placebo-controlled, double-blind, phase 3 trial. Lancet Oncol 2016;17:509-18.  Back to cited text no. 14
    
15.
Aapro M, Rugo H, Rossi G, Rizzi G, Borroni ME, Bondarenko I, et al. 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 2014;25:1328-33.  Back to cited text no. 15
    
16.
Navari RM, Rapoport BL, Powers D, Arora S, Clark-Snow R. Rolapitant for the prevention of nausea in patients receiving highly or moderately emetogenic chemotherapy. Cancer Med 2018;7:2943-2950.  Back to cited text no. 16
    
17.
Navari RM, Gray SE, Kerr AC. Olanzapine versus aprepitant for the prevention of chemotherapy-induced nausea and vomiting: A randomized phase III trial. J Support Oncol 2011;9:188-95.  Back to cited text no. 17
    
18.
Tan L, Liu J, Liu X, Chen J, Yan Z, Yang H, et al. Clinical research of olanzapine for prevention of chemotherapy-induced nausea and vomiting. J Exp Clin Cancer Res 2009;28:131.  Back to cited text no. 18
    
19.
Chanthawong S, Lim YH, Subongkot S, Chan A, Andalusia R, Bustamam RS, et al. Cost-effectiveness analysis of olanzapine-containing antiemetic therapy for managing highly emetogenic chemotherapy in Southeast Asia: A multinational study. Support Care Cancer 2019;27:1109-19.  Back to cited text no. 19
    



 
 
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  In this article
   Abstract
  Introduction
  Mechanism Of Action
  Discovery
  Approval
   Highly Emetogeni...
  Olanzapine Dose
   Olanzapine, Palo...
   Why Olanzapine-B...
  Guidelines
   Olanzapine, Palo...
  Cost-Effectiveness
  Conclusion
   References
   Article Tables

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