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The emerging emetogenicity of trifluridine/tipiracil (TAS‑102) from patient self-reporting: a multicenter, prospective, observational study

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Abstract

Background

Trifluridine/tipiracil (TAS-102) is an oral anticancer drug with adequate efficacy in unresectable colorectal cancer, but frequently also induces chemotherapy-induced nausea and vomiting (CINV). To investigate the occurrence of CINV and antiemetic therapy in patients with colorectal cancer treated with TAS-102 (JASCC-CINV 2001).

Methods

We conducted a multicenter, prospective, observational study in patients with colorectal cancer who received TAS-102 without dose reduction for the first time. Primary endpoint was the incidence of vomiting during the overall period. Secondary endpoints were the incidence of nausea, significant nausea, anorexia, other adverse events (constipation, diarrhea, insomnia, fatigue, dysgeusia) and patient satisfaction. Patient diaries were used for primary and secondary endpoints. All adverse events were subjectively assessed using PRO-CTCAE ver 1.0. and CTCAE ver 5.0.

Results

Data from 100 of the 119 enrolled patients were analyzed. The incidence of vomiting, nausea, and significant nausea was 13%, 67%, and 36%, respectively. The incidence of vomiting in patients with and without prophylactic antiemetic therapy were 20.8% and 10.5%, respectively. Prophylactic antiemetics were given to 24% of patients, of whom 70% received D2 antagonists. Multivariate Cox proportional hazards analysis showed that experience of CINV in previous treatment tended to be associated with vomiting (hazard ratio [HR]: 7.13, 95% confidence interval [CI]: 0.87–58.5, P = 0.07), whereas prophylactic antiemetic administration was not (HR: 1.61, 95 CI: 0.50–5.21, P = 0.43). With regard to patient satisfaction, the proportion of patients who were "very satisfied," "satisfied," "slightly satisfied" or "somewhat satisfied" was 81.8%.

Conclusions

The low incidence of vomiting and high patient satisfaction suggest that TAS-102 does not require the use of uniform prophylactic antiemetic treatments. However, patients with the experience of CINV in previous treatment might require prophylactic antiemetic treatment.

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Data availability

No datasets were generated or analysed during the current study.

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Acknowledgements

We thank all the patients and their families for participating in this study. We thank Dr. Takuma Ishihara (Gifu University Hospital) for his support in statistical analysis. We thank the Independent Alliance Data Center, and Ms. Mami Matsumaru (Gifu University Hospital). We would like to express our sincere gratitude to our advisors, Prof. Kazuo Tamura (Fukuoka University School of Medicine), Prof. Toshiaki Saeki (Saitama Medical University International Medical Center), Prof. Keisuke Aiba (The Jikei University School of Medicine), Prof. Mitsue Saito (Juntendo University School of Medicine), Dr. Kenji Okita (Sapporo Medical University School of Medicine) and, Pres. Kazuhiro Yoshida (Gifu University) for their invaluable guidance and support throughout this research project.

Funding

This study did not receive funding from any funding source.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Gifu University Hospital, Gifu, Japan

    Hironori Fujii, Daichi Watanabe, Akio Suzuki & Hirotoshi Iihara

  2. Department of Pharmacy, Miyagi Cancer Center, Miyagi, Japan

    Masami Tsuchiya, Katsuhisa Hayashi & Takashi Uchida

  3. Innovative and Clinical Research Promotion Center, Gifu University Hospital, Gifu, Japan

    Daichi Watanabe

  4. Department of Pharmacy, National Cancer Center Hospital, Tokyo, Japan

    Ryo Otsuka, Miki Chin, Hironobu Hashimoto & Akiko Kubo

  5. Department of Pharmacy, Teine Keijinkai Hospital, Hokkaido, Japan

    Daisuke Hirate & Naomi Matsunami

  6. Department of Pharmacy, Osaka City University Hospital, Osaka, Japan

    Katsuyuki Takahashi & Masaya Takahashi

  7. Department of Pharmacy, Ogaki Municipal Hospital, Gifu, Japan

    Makiko Go

  8. Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan

    Toshihiro Kudo, Akiko Hasegawa & Junichi Nishimura

  9. Department of Pharmacy, Aichi Cancer Center Hospital, Aichi, Japan

    Kazuhiro Shimomura

  10. Department of Pharmacotherapeutics and Informatics, Fujita Health University, Aichi, Japan

    Yosuke Ando

  11. First Department of Medicine, Hamamatsu University School of Medicine, Shizuoka, Japan

    Shinya Tani & Naoki Inui

  12. Department of Gastroenterological Surgery, Pediatric Surgery, Gifu University Graduate School of Medicine, Gifu, Japan

    Takao Takahashi & Nobuhisa Matsuhashi

  13. Department of Surgery, Seino Kosei Hospital, Gifu Seino Medical Center, Gifu, Japan

    Takao Takahashi

  14. Laboratory of Advanced Medical Pharmacy, Gifu Pharmaceutical University, Gifu, Japan

    Akio Suzuki

  15. Patient Safety Division, Gifu University Hospital, Gifu, Japan

    Hirotoshi Iihara

  16. Laboratory of Community Pharmaceutical Practice and Science, Gifu Pharmaceutical University, Gifu, Japan

    Hirotoshi Iihara

Authors
  1. Hironori Fujii
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  2. Masami Tsuchiya
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  6. Katsuyuki Takahashi
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  7. Makiko Go
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  8. Toshihiro Kudo
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  9. Kazuhiro Shimomura
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  11. Shinya Tani
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  13. Katsuhisa Hayashi
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  14. Miki Chin
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  19. Hironobu Hashimoto
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Contributions

H.I. and D.W. had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis. Concept and design: H.I., N.I., J.N., H.H., H.F., and D.W. Acquisition, analysis, or interpretation of data: H.I., N.I., J.N., H.F., M.T., D.W., R.O., D.H., K.T., M.G., T.K., K.S., Y.A., S.T., T.T., K.H., M.C., N.M., M.T., A.H., T.U., H.H., A.K., N.M., and A.S. Drafting of the manuscript: H.F., H.I., and D.W. Critical revision of the manuscript for important intellectual content: H.I., H.F., N.I., J.N., N.H. Statistical analysis: D.W. All authors reviewed the manuscript.

Corresponding author

Correspondence to Hirotoshi Iihara.

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Competing interests

H Fujii has received honoraria for lectures from Ono Pharm, Chugai Pharm, and Taiho Pharm. M Tsuchiya has received honoraria for lectures from Ono Pharm, Chugai Pharm, Taiho Pharm, Sun Pharm and Kyowa Kirin. D Watanabe has received honoraria for lectures from Chugai Pharm. D Hirate has received honoraria for lectures from Taiho Pharm, Daiichi Sankyo, Eli Lilly and Company, Pfizer Eisai, Takeda Pharm, Bristol Myers Squibb, EA Pharma, MSD Japan, Kyowa Kirin, Chugai Pharm, Yakult Honsha, Nippon Kayaku, Eisai, Meiji Seika Pharma, Merck Bio Pharma, AstraZeneca plc and Sun Pharma. Y Ando has received honoraria for lectures from Yakult Honsha, Taiho Pharm, Daiichi Sankyo, Pfizer Eisai. N Matsunami has received honoraria for lectures from Pfizer Eisai, Daiichi Sankyo and Eli Lilly and Company. N Matsuhashi has received both honoraria for lectures and grants made to institution from Taiho Pharm. J Nishimura has received honoraria for lectures from Taiho Pharm. N Inui has received honoraria for lectures from Taiho Pharm, AstraZeneca plc and Chugai Pharm. A Suzuki has received honoraria for lectures from Toa Eiyo, Asahi Kasei Pharma, Daiichi Sankyo, Pfizer Eisai, Nippon Shinyaku, Celltrion Healthcare Japan, Otsuka Pharm, Sandoz, Tsumura, Nipro, Taiho Pharm, Kyowa Kirin, Nippon Chemiphar, Japan Blood Products Organization, Takeda Pharm, and Nippon Boehringer Ingelheim and grants made to institution from Nippon Kayaku, Asahi Kasei Pharma, Chugai Pharm, Taiho Pharm, Daiichi Sankyo, Japan Blood Products Organization, Mochida Pharm, Sun Pharma and consulting fees from Nippon Kayaku. H Iihara has received honoraria for lectures from Taiho Pharm, Chugai Pharma, Yakult Honsha, Astellas Pharma, Eli Lilly and Company, Daiichi Sankyo, AstraZeneca plc, Nippon Kayaku, Ono Pharm, and Nippon Boehringer Ingelheim; and consulting fees from Pfizer Eisai and Taiho Pharm. The other authors have no conflicts of interest.

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Fujii, H., Tsuchiya, M., Watanabe, D. et al. The emerging emetogenicity of trifluridine/tipiracil (TAS‑102) from patient self-reporting: a multicenter, prospective, observational study. Support Care Cancer 32, 291 (2024). https://doi.org/10.1007/s00520-024-08498-z

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