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Severity and predictive factors of adverse events in pemetrexed-containing chemotherapy for non-small cell lung cancer

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Abstract

Pemetrexed is a key anticancer agent for treatment of advanced non-small cell lung cancer (NSCLC). Pemetrexed is generally well tolerated, but individual-patient differences exist in severity of adverse events. Our study aimed to characterize the adverse events of pemetrexed that result in discontinuation of chemotherapy and to identify risk factors associated with those adverse events. We retrospectively studied the incidence of adverse events in 257 patients with NSCLC who received pemetrexed (P) with or without bevacizumab (B) and/or carboplatin (C): P, PB, CP, or CPB. Patients whose chemotherapy was discontinued were divided into two groups according to adverse events and disease progression. Grade 2/3 nausea, fatigue with P and PB, and rash with CP and CPB occurred more frequent in the adverse events group than in the disease progression group. Multivariate analysis indicated that grade 2/3 nausea [odds ratio (OR) 9.94; 95% confidence interval (CI) 1.46–67.37; p = 0.01] and fatigue (OR 10.62; CI 1.60–70.20; p = 0.01) with P or PB, and rash (OR 6.12; CI 1.34–27.88; p = 0.01) with CP or CPB, were independent risk factors for discontinuation of chemotherapy. Administration of dexamethasone at doses less than 4 mg after the day of pemetrexed administration was associated with nausea following P or PB (OR 11.08; 95% CI 1.02–119.95; p = 0.04). Grade 2/3 nausea and fatigue with P or PB, and rash with CP or CPB, were associated with discontinuation of chemotherapy.

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Acknowledgements

We would like to thank the participating patients for their contribution to this study.

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Authors and Affiliations

  1. Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine, Faculty of Medicine, Saga University, Saga, 849-8501, Japan

    Tsuyoshi Miyahara, Naoko Sueoka-Aragane, Kazutoshi Komiya, Tomomi Nakamura, Chiho Nakashima, Tomonori Abe & Shinya Kimura

  2. Department of Pharmacy, Saga-Ken Medical Centre Koseikan, Saga, Japan

    Tsuyoshi Miyahara & Hisashi Matsunaga

  3. Division of Respiratory Medicine, Saga-Ken Medical Centre Koseikan, Saga, Japan

    Kentaro Iwanaga

  4. Division of Medical Oncology, Saga-Ken Medical Centre Koseikan, Saga, Japan

    Norio Ureshino

Authors
  1. Tsuyoshi Miyahara
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  2. Naoko Sueoka-Aragane
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  3. Kentaro Iwanaga
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  5. Kazutoshi Komiya
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  8. Tomonori Abe
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Corresponding author

Correspondence to Naoko Sueoka-Aragane.

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Conflict of interest

S.K. and N.S.-A. have received research grants from SK, Eli Lilly, and Chugai Pharmaceutical for another research project.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. For this type of study, formal consent is not required.

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Miyahara, T., Sueoka-Aragane, N., Iwanaga, K. et al. Severity and predictive factors of adverse events in pemetrexed-containing chemotherapy for non-small cell lung cancer. Med Oncol 34, 195 (2017). https://doi.org/10.1007/s12032-017-1053-8

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  • DOI: https://doi.org/10.1007/s12032-017-1053-8

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