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A phase II study of nanoparticle albumin-bound paclitaxel plus carboplatin as the first-line therapy in elderly patients with previously untreated advanced non-small cell lung cancer

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Abstract

Introduction

The objective of this clinical trial was to explore the efficacy and tolerability of first-line chemotherapy with nanoparticle albumin-bound paclitaxel (nab-paclitaxel), a novel agent that uses a drug delivery system, plus carboplatin, in elderly Japanese patients with advanced non-small cell lung cancer (NSCLC).

Patients and methods

In this phase II, single-arm, open-label, single-institutional study, we aimed to enroll 37 elderly patients, aged more than 70 years, with advanced NSCLC of performance status 0 or 1. The patients received each cycle of first-line therapy consisting of 100 mg/m2 nab-paclitaxel intravenously administered on days 1, 8, and 15 of each 21-day cycle, plus carboplatin area under curve 6 on day 1 of each 21-day cycle, for up to six cycles. The primary end point was determining the objective response rate, and secondary endpoints were progression-free survival, overall survival, and safety.

Results

The study was interrupted early because of two treatment-related deaths and 1 life-threatening severe adverse event; therefore, only 10 patients (median age, 77 years; range 71–82 years) were enrolled. The primary end point of the objective response was 50 % for the 10 patients analyzed. Progression-free survival was 4.48 months [95 % confidence interval (CI) 0.36–6.44], and overall survival was 7.89 months (95 % CI 0.36–26.88). Common treatment-related adverse events higher than grade 2 included decreased neutrophil counts, anemia, decreased albumin, anorexia, and peripheral neuropathy. Regarding severe adverse events, two patients had febrile neutropenia and lung infection. Two patients died, and one patient had febrile neutropenia with intubation during the first cycle. The Data and Safety Monitoring Committee therefore recommended interruption of patient enrollment.

Conclusion

Nab-paclitaxel plus carboplatin, without dose reduction, is indicated to be toxic and intolerable as first-line chemotherapy in elderly Japanese patients with advanced NSCLC. Care must be taken when extrapolating the results of a clinical trial into clinical practice, particularly when the resulting subgroup analysis is of elderly patients because this patient group is composed of a heterogeneous population.

Clinical trial registration

UMIN-CTR identifier: UMIN000010738.

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Acknowledgments

The authors thank Dr. Kan Kato (Tokyo Kensei Hospital) and Dr. Shingo Miyamoto (Japan Red Cross Medical Center) for management and recommending the present clinical trial as the Data and Safety Monitoring Committee. The authors would also like to thank Makoto Saito (the Senior Biostatistician in Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital) for statistical advice and Enago (https://www.enago.jp//) for the English language review.

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Authors and Affiliations

  1. Department of Thoracic Oncology and Respiratory Medicine, Tokyo Metropolitan Cancer and Infectious diseases Center Komagome Hospital, Honkomagome 3-18-22, Bunkyo, Tokyo, 113-8677, Japan

    Yusuke Okuma, Yukio Hosomi, Satoshi Takahashi, Yoshiro Nakahara, Kageaki Watanabe, Makoto Nagamata & Yusuke Takagi

  2. Division of Oncology, Research Center for Medical Sciences, The Jikei University School of Medicine, Minato, Tokyo, 105-8461, Japan

    Yusuke Okuma

  3. Department of Pulmonary Medicine and Oncology, Graduate School of Medicine, Nippon Medical School, Bunkyo, Tokyo, 113-8603, Japan

    Satoshi Takahashi

  4. Department of Respiratory Medicine, Kitasato University School of Medicine, Sagamihara, Kanagawa, 252-0375, Japan

    Yoshiro Nakahara

  5. MSD K.K., Chiyoda, Tokyo, 102-8667, Japan

    Yusuke Takagi

  6. Department of Respiratory Medicine, Fujieda Municipal General Hospital, Fujieda, Shizuoka, 426-8677, Japan

    Shinichiro Mikura

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  1. Yusuke Okuma
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Correspondence to Yusuke Okuma.

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Okuma, Y., Hosomi, Y., Takahashi, S. et al. A phase II study of nanoparticle albumin-bound paclitaxel plus carboplatin as the first-line therapy in elderly patients with previously untreated advanced non-small cell lung cancer. Cancer Chemother Pharmacol 78, 383–388 (2016). https://doi.org/10.1007/s00280-016-3092-9

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  • DOI: https://doi.org/10.1007/s00280-016-3092-9

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