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Phase I study of weekly nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in elderly patients with unresectable locally advanced non-small cell lung cancer

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Summary

Few clinical studies have been designed for elderly patients with locally advanced non-small cell lung cancer (NSCLC). We conducted a phase I study to evaluate the tolerability of carboplatin/nab-paclitaxel and concurrent thoracic radiotherapy in elderly patients with locally advanced NSCLC. The eligibility criteria were: unresectable stage III NSCLC, performance status 0 or 1, and age ≥ 75 years. Eligible patients received 6 weeks of weekly carboplatin/nab-paclitaxel and concurrent thoracic radiotherapy with a total dose of 64 Gy in 32 fractions. Carboplatin was fixed to an area under the plasma concentration time curve (AUC) of 2 mg/mL/min, and the recommended dose of nab-paclitaxel was evaluated using a dose-escalation study (30 or 40 mg/m2). Tolerability at the recommended dose was evaluated in an expansion study. Nineteen patients were enrolled at four institutions, all of whom were eligible and assessable. The recommended nab-paclitaxel dose was set at 30 mg/m2 because two patients experienced dose-limiting toxicity at 40 mg/m2. The treatment completion rate of the 17 patients analyzed at the recommended dose was 100% (80% confidence interval (CI), 83.8–100%). The overall response rate was 76.5%, and the median progression free survival was 13.4 months (95% CI, 4.2–21.4 months). Common grade 3 and 4 toxicities included leukopenia (23.5%), neutropenia (17.6%), anemia (5.9%), and infection (5.9%). One treatment-related death due to pneumonitis was observed six months after the end of the study. In conclusion, carboplatin/nab-paclitaxel and concurrent thoracic radiotherapy show good tolerability and exhibit promising efficacy in elderly patients with locally advanced NSCLC. This trial was registered with the Japan Registry of Clinical Trials on March 11, 2019 (trial no. jRCTs042180077).

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Data availability

The remaining data that support the findings of this study are available from the corresponding author upon reasonable request. The data are not publicly available due to privacy or ethical restrictions.

Change history

  • 20 September 2021

    Springer Nature’s version of this paper was updated to include the supplementary materials.

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Acknowledgements

We thank all patients who participated in this study, their families, and caregivers.

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. Division of Thoracic Oncology, Shizuoka Cancer Center, Shizuoka, Japan

    Shota Omori & Toshiaki Takahashi

  2. Division of Radiation Therapy, Shizuoka Cancer Center, Shizuoka, Japan

    Hideyuki Harada

  3. Department of Biostatistics, Shizuoka Cancer Center, Shizuoka, Japan

    Keita Mori

  4. Department of Thoracic Medical Oncology, Oita Prefectural Hospital, Oita, Japan

    Yasushi Hisamatsu & Ryotaro Morinaga

  5. Department of Medical Oncology, Osaka City General Hospital, Osaka, Japan

    Yuko Tsuboguchi & Haruko Daga

  6. Department of Thoracic Oncology, Kansai Medical University Hospital, Osaka, Japan

    Hiroshige Yoshioka & Takayasu Kurata

Authors
  1. Shota Omori
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Contributions

Shota Omori: developing the study concept and design, recruitment of patients, writing the manuscript, responsibility for the integrity of the data and accuracy of the data analysis; Hideyuki Harada: developing the study concept and design, recruitment of patients, and reviewing the manuscript; Keita Mori (Primary biostatistician of the study): developing the study concept and design, statistical analysis, and reviewing the manuscript; Yasushi Hisamatsu: recruitment of patients and reviewing the manuscript; Yuko Tsuboguchi: recruitment of patients and reviewing the manuscript; Hiroshige Yoshioka: recruitment of patients and reviewing the manuscript; Ryotaro Morinaga: recruitment of patients and reviewing the manuscript; Haruko Daga: recruitment of patients and reviewing the manuscript; Takayasu Kurata: recruitment of patients and reviewing the manuscript; Toshiaki Takahashi (Corresponding Author): recruitment of patients, reviewing the manuscript, and supervising this clinical trial.

Corresponding author

Correspondence to Toshiaki Takahashi.

Ethics declarations

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional review board and the 1964 Helsinki declaration and its later amendments or with comparable ethical standards. This study was reviewed and approved by the certified review board of Shizuoka Cancer Center and registered with the Japan Registry of Clinical Trials on March 11, 2019 (trial no. jRCTs042180077).

Consent to participate

All patients provided written informed consent before enrollment.

Conflicts of interest

Shota Omori received honoraria from Taiho-Pharma, Chugai-Pharma, Daiichi-Sankyo, Amgen, AstraZeneca, Ono-Pharma, and Novartis outside the submitted work. Hideyuki Harada received honoraria from AstraZeneca, Chugai-Pharma, Daiichi-Sankyo, Novartis, Eli Lilly, Pfizer, and Brainlab outside the submitted work. Hiroshige Yoshioka received honoraria from Taiho-Pharma, Delta-Fly Pharma, Eli Lilly, Chugai-Pharma, AstraZeneca, Ono-Pharma, MSD, Novartis, Kyowa Hakko Kirin, Daiichi-Sankyo, Nippon Kayaku, Otsuka-Pharma, and Pfizer outside the submitted work. Haruko Daga received honoraria from Chugai-Pharma and Ono-Pharma and research funding from AstraZeneca, Chugai-Pharma, and Pfizer outside the submitted work. Takayasu Kurata received honoraria from AstraZeneca, Ono-Pharma, Bristol-Myers Squibb, Chugai-Pharma, Eli Lilly, and Boehringer Ingelheim, and MSD research funding from MSD, AstraZeneca, Eli Lilly, Takeda-Pharma, and Ono-Pharma outside the submitted work. Toshiaki Takahashi received honoraria from AstraZeneca, Boehringer Ingelheim, Chugai-Pharma, Eli Lilly, MSD, Ono-Pharma, Roche Diagnostics, and Pfizer, and research funding from AstraZeneca, Boehringer Ingelheim, Chugai-Pharma, Eli Lilly, Ono-Pharma, MSD, and Pfizer outside the submitted work. The other authors declare no conflicts of interest.

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Omori, S., Harada, H., Mori, K. et al. Phase I study of weekly nab-paclitaxel plus carboplatin and concurrent thoracic radiotherapy in elderly patients with unresectable locally advanced non-small cell lung cancer. Invest New Drugs 40, 106–114 (2022). https://doi.org/10.1007/s10637-021-01155-w

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