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Phase I study of S-1 plus paclitaxel combination therapy as a first-line treatment in elderly patients with advanced non-small cell lung cancer

  • PHASE I STUDIES
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Summary

This phase I study was aimed at determining the maximum tolerated dose (MTD) and recommended dose (RD) for oral S-1 plus paclitaxel combination therapy in elderly patients with non-small cell lung cancer (NSCLC). Chemotherapy-naïve patients (age, >70 years) with stage III/IV NSCLC were treated with paclitaxel intravenously at four dose levels (DLs), 60, 70, 80, and 90 mg/m2, on day 1 and 8, and with S-1 (80 mg/m2) orally on days 1–14 every 3 weeks. MTD was defined as the dose at which two of the initial three patients experienced dose-limiting toxicities (DLTs). Three patients were added when the initial three patients experienced DLTs. The dose administered in three of the six patients with DLTs met the definition of MTD. The RD was defined as a dose 1 DL below the MTD. Fifteen patients including six on DL 1 and three each on DLs 2, 3, and 4 were enrolled. One patient experienced a DLT (febrile neutropenia) at DL 1. The remaining DLTs were noted at DL 4 (in one patient each): febrile neutropenia, grade (G) 3 skin rash, G3 diarrhea, G3 stomatitis, and G3 international normalized ratio (INR) elevation. The MTD of paclitaxel was 90 mg/m2. The RD for both S-1 and paclitaxel was 80 mg/m2 (DL 3). The response rate was 45.5% (8 of 15 patients achieved a partial response). In conclusion, the RD of both S-1 and paclitaxel was 80 mg/m2 in the combination therapy for chemotherapy-naïve patients with advanced NSCLC.

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Acknowledgments

We thank the patients, their families, and all investigators involved in this study. We are also grateful to Tomoko Shoji for help with office work.

Funding

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

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Authors and Affiliations

  1. Department of Pulmonary Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, Kyoto, 602-8566, Japan

    Yusuke Chihara, Nobuyo Tamiya, Tatsuya Imabayashi, Yoshiko Kaneko, Tadaaki Yamada, Junji Uchino & Koichi Takayama

  2. Department of Pulmonary Medicine, Kyoto Chubu Medical Center, Kyoto, Japan

    Koji Date

  3. Department of Pulmonary Medicine, Kyoto Kuramaguchi Medical Center, Kyoto, Japan

    Yoshizumi Takemura

  4. Yakushiyama Hospital, Kyoto, Japan

    Yoshihito Kohno

  5. Department of Pulmonary Medicine, Nishijin Hospital, Kyoto, Japan

    Mikio Ueda

  6. Kyoto Kojo Hokenkai Clinic, Kyoto, Japan

    Taichiro Arimoto

  7. Department of Pulmonary Medicine, Showa General Hospital, Tokyo, Japan

    Yoshinobu Iwasaki

Authors
  1. Yusuke Chihara
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  2. Koji Date
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  3. Yoshizumi Takemura
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  4. Nobuyo Tamiya
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  5. Yoshihito Kohno
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  6. Tatsuya Imabayashi
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  7. Yoshiko Kaneko
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  8. Tadaaki Yamada
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  9. Mikio Ueda
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  10. Taichiro Arimoto
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  11. Junji Uchino
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  12. Yoshinobu Iwasaki
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  13. Koichi Takayama
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Corresponding author

Correspondence to Junji Uchino.

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Conflicts of interests

J Uchino reports grants from Eli Lilly Japan K.K., outside the submitted work. T Yamada reports grants from Nippon Boehringer Ingelheim Co., Ltd., and Ono Pharmaceutical Co., Ltd., outside the submitted work. K Takayama reports grants from Chugai-Roche Co., grants from Ono Pharmaceutical Co., personal fees from Astrazeneca Co., personal fees from Chugai-Roche Co., personal fees from MSD-Merck Co., personal fees from Eli Lilly Co., personal fees from Boehringer-Ingelheim Co., personal fees from Daiichi-Sankyo Co., outside the submitted work. The other authors have no conflict of interest to declare.

Ethical approval

All procedures performed in human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all participants included in the study.

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Chihara, Y., Date, K., Takemura, Y. et al. Phase I study of S-1 plus paclitaxel combination therapy as a first-line treatment in elderly patients with advanced non-small cell lung cancer. Invest New Drugs 37, 291–296 (2019). https://doi.org/10.1007/s10637-018-0656-z

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  • DOI: https://doi.org/10.1007/s10637-018-0656-z

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