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Should palonosetron be a preferred 5-HT3 receptor antagonist for chemotherapy-induced nausea and vomiting? An updated systematic review and meta-analysis

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Abstract

Purpose

Chemotherapy-induced nausea and vomiting (CINV) continues to be a common side effect of systemic anticancer therapy, decreasing quality of life and increasing resource utilization. The aim of this meta-analysis was to investigate the comparative efficacy and safety of palonosetron relative to other 5-HT3RAs.

Methods

A literature search was carried out in Ovid MEDLINE, Embase, and Cochrane Central Register of Controlled Trials. Full-text references were then screened and included in this meta-analysis if they were an RCT and had adequate data regarding one of the five primary endpoints—complete response (CR), complete control (CC), no emesis, no nausea, or no rescue medications.

Results

A total of 24 RCTs were included in this review. Palonosetron was statistically superior to other 5-HT3RAs for 10 of the 19 assessed endpoints. Only one endpoint—emesis in the overall phase—had noticeable more favorable data for palonosetron to the point that it approached the 10% risk difference (RD) threshold as specified by the MASCC/ESMO antiemetic panel; another two endpoints (CR in the overall phase and nausea in the delayed phase) approached the 10% threshold.

Conclusions

Palonosetron seems to be more efficacious and safe than other 5-HT3RAs—statistically superior in 10 of 19 endpoints. It is, however, only clinically significant in one endpoint and approached clinically significant difference in another two endpoints. Within the limits of this meta-analysis, our results indicate that palonosetron may not be as superior in efficacy and safety as reported in a previous meta-analysis, and supports the recent MASCC/ESMO, ASCO, and NCCN guidelines in not generally indicating palonosetron as the 5-HT3RA of choice.

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Authors and Affiliations

  1. Odette Cancer Centre, Sunnybrook Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, ON, M4N 3M5, Canada

    Ronald Chow, May Tsao, Marko Popovic, Leonard Chiu, Milica Milakovic, Henry Lam & Carlo DeAngelis

  2. Princess Margaret Cancer Centre, University of Toronto, Toronto, ON, Canada

    David G. Warr

  3. University of Alabama Birmingham School of Medicine, Birmingham, AL, USA

    Rudolph M. Navari

  4. Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, ON, Canada

    Carlo DeAngelis

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  1. Ronald Chow
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Appendices

Appendix 1

Table 1 Search strategy
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Appendix 2

Fig. 7
figure 7

PRISMA flow diagram

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Appendix 3

Table 2 Characteristics of included randomized controlled trials among adults
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Appendix 4

Table 3 Absolute risk difference between palonosetron versus other 5-HT3RAs intervention arms for all included efficacy chemotherapy-induced nausea and vomiting endpoints among adult studies
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Appendix 5

Fig. 8
figure 8figure 8

Efficacy of palonosetron compared with other 5-HT3RAs in the prophylaxis of chemotherapy-induced nausea and vomiting—complete response. a Acute phase, b delayed phase, and c overall phase

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Fig. 9
figure 9

Efficacy of palonosetron compared with other 5-HT3RAs in the prophylaxis of chemotherapy-induced nausea and vomiting—complete control. a Acute phase, b delayed phase, and c overall phase

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Fig. 10
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Efficacy of palonosetron compared with other 5-HT3RAs in the prophylaxis of chemotherapy-induced nausea and vomiting—no emesis. a Acute phase, b delayed phase, and c overall phase

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Appendix 8

Fig. 11
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Efficacy of palonosetron compared with other 5-HT3RAs in the prophylaxis of chemotherapy-induced nausea and vomiting—no nausea. a Acute phase, b delayed phase, and c overall phase

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Appendix 9

Fig. 12
figure 12

Efficacy of palonosetron compared with other 5-HT3RAs in the prophylaxis of chemotherapy-induced nausea and vomiting—no rescue medication. a Acute phase, b delayed phase, and c overall phase

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Appendix 10

Fig. 13
figure 13figure 13

Safety of palonosetron compared with other 5-HT3RAs in the prophylaxis of chemotherapy-induced nausea and vomiting—treatment-related adverse events. a Constipation, b headache, c dizziness, and d diarrhea

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Chow, R., Warr, D.G., Navari, R.M. et al. 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, 2519–2549 (2018). https://doi.org/10.1007/s00520-018-4237-7

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