A multicenter, phase II trial of triplet antiemetic therapy with palonosetron, aprepitant, and olanzapine for highly emetogenic chemotherapy in breast cancer (PATROL-II).

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Olanzapine*/administration & dosage ; Olanzapine*/adverse effects ; Olanzapine*/therapeutic use ; Aprepitant*/therapeutic use ; Aprepitant*/administration & dosage ; Palonosetron*/therapeutic use ; Palonosetron*/administration & dosage ; Breast Neoplasms*/drug therapy ; Antiemetics*/therapeutic use ; Antiemetics*/administration & dosage ; Vomiting*/chemically induced ; Vomiting*/prevention & control ; Vomiting*/drug therapy ; Nausea*/chemically induced ; Nausea*/drug therapy ; Nausea*/prevention & control; Humans ; Female ; Middle Aged ; Aged ; Adult ; Antineoplastic Combined Chemotherapy Protocols/adverse effects ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Treatment Outcome ; Dexamethasone/administration & dosage ; Dexamethasone/therapeutic use ; Dexamethasone/adverse effects

Dexamethasone is an antiemetic drug widely used to prevent nausea and vomiting caused by anticancer drugs. However, dexamethasone can cause several side effects even after short-term administration. Therefore, the development of dexamethasone-free antiemetic therapies has been recognized as an important challenge. The objective of this study was to investigate the efficacy and safety of palonosetron, aprepitant, and olanzapine. Patients who were chemotherapy-naïve and scheduled to receive highly emetogenic chemotherapy for breast cancer were enrolled and assessed for nausea and vomiting occurring within 120 h after the start of chemotherapy. The primary endpoint was the total control (TC) rate of overall phases. Secondary endpoints included the complete response (CR) rate, which was evaluated during the acute, delayed, and overall phases. A total of 88 patients were enrolled from eight centers in Japan, of whom 84 were included in the analysis. The proportion of patients achieving TC throughout the overall period was 17.1%. Similarly, CR and CC rates for the overall period were 43.4% and 39.5%, respectively. Frequently reported adverse events were loss of appetite and constipation, with rates of 52.4% and 50.0%, respectively. The primary endpoint was not achieved. Therefore, antiemetic therapy without dexamethasone shows an inadequate effect on nausea, and it is generally advisable to avoid omitting dexamethasone. However, in the overall period, both CR and CC were comparable to conventional three-drug combination therapy. Thus, in patients unable to use dexamethasone, replacing it with olanzapine could be an option.Trial registration number: UMIN 000038644, November 20, 2019. The date of first trial registration: 13/03/2020.
Competing Interests: Declarations Competing interests The authors declare no competing interests. Ethical approval This study was conducted in accordance with Ethical Guidelines for Medical and Health Research Involving Human Subjects published by Japan’s Ministry of Education, Culture, Sports, Science and Technology and the Ministry of Health, Labour and Welfare, Japan, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. Informed consent Written, informed consent was obtained from all participants.
(© 2024. The Author(s).)

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Keywords: Breast cancer; CINV; Dexamethasone; Olanzapine; Phase II

N7U69T4SZR (Olanzapine)
1NF15YR6UY (Aprepitant)
5D06587D6R (Palonosetron)
0 (Antiemetics)
7S5I7G3JQL (Dexamethasone)

Date Created: 20241116 Date Completed: 20241117 Latest Revision: 20241121

20241122

PMC11569132

10.1038/s41598-024-79781-6

39550497