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A phase II study of pemetrexed plus carboplatin followed by maintenance pemetrexed as first-line chemotherapy for elderly patients with advanced non-squamous non-small cell lung cancer

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Abstract

A phase I study recommended carboplatin (CBDCA, area under the curve = 5) plus pemetrexed (PEM, 500 mg/m2) for elderly patients (≥75-years old) with non-squamous non-small cell lung cancer (NSCLC). PEM maintenance therapy was well tolerated. We conducted a multicenter phase II trial to evaluate the efficacy and safety of this regimen in elderly patients with NSCLC. Four courses of CBDCA plus PEM, followed by PEM, were administered. The primary endpoint was the 1-year overall survival (OS) rate, and the secondary endpoints were OS, progression-free survival (PFS), response rate (RR), and safety. Thirty-four patients (median age, 77 years) were enrolled between June 2012 and May 2013. The median observation time was 22.7 months. The primary endpoint of the 1-year OS rate was 58.0 % (95 % confidence interval (CI) 42.9–78.4 %), and RR and disease control rate were 41.2 and 85.3 %, respectively. Fourteen patients had partial responses, 15 had stable disease, 4 had disease progression, and 1 was not evaluated. The maintenance therapy rate was 58.8 %. The median PFS was 5.7 months (95 % CI 3.9–8.9 months), and median OS was 20.5 months (95 % CI 10.0–infinity months). Grade ≥3 hematological adverse events included leucopenia (23.5 % of patients), neutropenia (55.9 %), anemia (35.3 %), and thrombocytopenia (20.6 %). Grade ≥3 non-hematological adverse events included febrile neutropenia (8.8 %), elevated aminotransferases (5.9 %), infection (23.5 %), and anorexia/fatigue (5.9 %). Four patients had interstitial lung diseases (ILD) and one died due to ILD. CBDCA plus PEM, followed by PEM, was effective and reasonably tolerated in chemotherapy-naïve elderly patients with non-squamous NSCLC.

Clinical Trial Registration This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (Trial Number UMIN 000004810).

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Acknowledgments

The authors wish to thank all the participating patients and all the cooperating colleges.

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Authors and Affiliations

  1. Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan

    Motohiro Tamiya & Tomonori Hirashima

  2. Department of Internal Medicine, National Hospital Organization Kinki-Chuo Chest Medical Center, 1180 Nakgasone-cho, Kita-ku, Sakai City, Osaka, 591-8555, Japan

    Akihiro Tamiya & Shinji Atagi

  3. Faculty of Medicine, Kinki University, Osaka, Japan

    Hiroyasu Kaneda & Kazuhiko Nakagawa

  4. National Cancer Center Hospital East, Chiba, Japan

    Kiyotaka Yoh & Koichi Goto

  5. Yokohama Municipal Citizen’s Hospital, Kanagawa, Japan

    Hiroaki Okamoto & Tsuneo Shimokawa

  6. Niigata Cancer Center Hospital, Niigata, Japan

    Tetsuya Abe & Hiroshi Tanaka

  7. Osaka City General Hospital, Osaka, Japan

    Haruko Daga & Koji Takeda

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  1. Motohiro Tamiya
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  2. Akihiro Tamiya
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  13. Tomonori Hirashima
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Correspondence to Akihiro Tamiya.

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Conflict of interest

Kiyotaka Yoh, Koji Takeda, and Shinji Atagi have received honoraria from Eli Lilly. Hiroaki Okamoto is currently receiving grants from Bristol Myers Squibb. Hirsoshi Tanaka, Kiyotaka Yoh, Kazuhiko Nakagawa, and Shinji Atagi are currently receiving grants from Eli Lilly. The remaining authors do not declare any conflicts of interest.

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Tamiya, M., Tamiya, A., Kaneda, H. et al. A phase II study of pemetrexed plus carboplatin followed by maintenance pemetrexed as first-line chemotherapy for elderly patients with advanced non-squamous non-small cell lung cancer. Med Oncol 33, 2 (2016). https://doi.org/10.1007/s12032-015-0715-7

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