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A phase II study of carboplatin plus weekly paclitaxel with bevacizumab for elderly patients with non-squamous non-small-cell lung cancer (NEJ016)

  • PHASE II STUDIES
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Summary

Background The efficacy and safety of bevacizumab in elderly patients with non-small cell lung cancer remain controversial. This study focused on both selecting fit elderly patients and overcoming interpatient variability with respect to pharmacodynamics. Methods Elderly (age: ≥70 years) patients with advanced non-squamous non-small cell lung cancer were enrolled. Patients with uncontrolled congestive heart failure and uncontrolled diabetes were excluded. The treatment regimen comprised carboplatin at an area under the curve of 5 mg/ml/min on day 1, paclitaxel at 90 mg/m2 on days 1 and 8, and bevacizumab at 15 mg/kg on day 1 every 21 days for up to 4 cycles, followed by maintenance bevacizumab. Dose reduction due to side effects was performed, with a wide range of doses of paclitaxel from 23 mg/m2/week to 60 mg/m2/week. Results Of the 36 patients entered, 38.9% required a dose reduction or cancellation of paclitaxel administration on day 8, and 75% patients were able to complete 4 cycles of triplet therapy. The response rate, primary endpoint, was 69.4% (95% confidence interval [CI]: 51.9–83.7). The median progression free survival and overall survival were 8.4 months and 29.2 months, respectively. The most common adverse events included neutropenia, hypertension, anemia, and infection. Although Grade ≥ 3 adverse events were observed in 24 patients (66.7%), there were no deaths due to toxicity. Conclusion Carboplatin plus weekly paclitaxel with bevacizumab is a feasible, effective first-line regimen for elderly non-small cell lung cancer patients. (UMIN00006622).

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Acknowledgements

We thank the patients and their families for their support and participation in this study. We thank the data management staff of The Tokyo Cooperative Oncology Group (TCOG) data center, especially Hiromi Odagiri, and the data analysis staff of the Medical TOUKEI Corporation. The authors also thank Dr. Keiichi Nagao, Dr. Yushi Nakai, and Dr. Hiroshi Tanaka for their assistance as the Safety Monitoring Committee.

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Authors and Affiliations

  1. Department of Internal Medicine, Niigata Cancer Center Hospital, 2-15-3, Kawagishicho, Chuo-ku, Niigata, 951-8566, Japan

    Satoru Miura

  2. Department of Respiratory Medicine and Infectious Disease, Niigata University Medical and Dental Hospital, Niigata, Japan

    Satoru Miura, Hiroshi Kagamu & Hirohisa Yoshizawa

  3. Department of Respiratory Medicine, Miyagi Cancer Center, Natori, Japan

    Makoto Maemondo

  4. Department of Respiratory Medicine, Nagaoka Chuo General Hospital, Nagaoka, Japan

    Akira Iwashima

  5. Center for Respiratory Diseases, Japan Community Health Care Organization Hokkaido Hospital, Sapporo, Japan

    Toshiyuki Harada

  6. Department of Pulmonary Medicine, Sendai Kousei Hospital, Sendai, Japan

    Shunichi Sugawara

  7. Department of Respiratory Medicine, Saitama Medical University International Medical Center, Hidaka, Japan

    Kunihiko Kobayashi & Hiroshi Kagamu

  8. Department of Palliative Medicine, Tohoku University School of Medicine, Sendai, Japan

    Akira Inoue

  9. Department of Thoracic Surgery, Omagari Kosei Medical Center, Akita, Japan

    Taku Nakagawa

  10. Department of Medical Oncology, Graduate School of Medicine, Chiba University, Chiba, Japan

    Yuichi Takiguchi

  11. Department of Respiratory Medicine, Saka General Hospital, Shiogama, Japan

    Hiroshi Watanabe

  12. Department of Internal Medicine, Niigata Prefectural Central Hospital, Joetsu, Japan

    Takashi Ishida

  13. Department of Respiratory Medicine, Saiseikai Niigata Daini Hospital, Niigata, Japan

    Masaki Terada

  14. Department of Pulmonary Medicine and Oncology, Nippon Medical School, Graduate School of Medicine, Tokyo, Japan

    Akihiko Gemma

  15. Department of Respiratory Medicine, Niigata Medical Center Hospital, Niigata, Japan

    Hirohisa Yoshizawa

Authors
  1. Satoru Miura
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  2. Makoto Maemondo
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  3. Akira Iwashima
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  4. Toshiyuki Harada
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  14. Akihiko Gemma
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  15. Hirohisa Yoshizawa
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Corresponding author

Correspondence to Satoru Miura.

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Conflict of interest

Satoru Miura, Shunichi Sugawara, Kunihiko Kobayashi, Yuichi Takiguchi and Akihiko Gemma has received lecture fees from Chugai Pharmaceutical Co. Makoto Maemondo, Akira Inoue Yuichi Takiguchi has received lecture fees from Chugai and Bristol-Myers Squibb. All other authors declare that they have no conflict of interest.

Financial support

This study was supported by the North East Japan Study Group (NEJSG).

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 Helsinki declaration and its later amendments or comparable ethical standards. This study was approved by the institutional review boards of all participating sites.

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All study participants provided written informed consent prior to enrollment.

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Miura, S., Maemondo, M., Iwashima, A. et al. A phase II study of carboplatin plus weekly paclitaxel with bevacizumab for elderly patients with non-squamous non-small-cell lung cancer (NEJ016). Invest New Drugs 35, 227–234 (2017). https://doi.org/10.1007/s10637-017-0436-1

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  • DOI: https://doi.org/10.1007/s10637-017-0436-1

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