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Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet chemotherapy for advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations

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Abstract

Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), is an effective treatment for advanced non-small cell lung cancer (NSCLC) in patients with activating EGFR mutations. However, there have been little evidence-based studies of gefitinib in combination with platinum-doublet therapy in these patients. We performed a phase II trial to determine the efficacy and safety of triplet chemotherapy with gefitinib, carboplatin, and S-1 as a first-line treatment. This was a multicentre, single-arm, phase II trial of carboplatin, S-1, and gefitinib in advanced NSCLC patients with activating EGFR mutations. Patients received four courses of these drugs in 3–4 week cycles. In each cycle, carboplatin (area under curve = 5) was administered on day 1, S-1 (80 mg/m2) on days 1–14, and gefitinib (250 mg) every day. Subsequently, the same regimen without carboplatin was administered until disease progression or unacceptable toxicity occurred. The 1-year progression-free survival (PFS) was the primary endpoint, while response rate (RR), PFS, overall survival (OS), and safety were secondary endpoints. Thirty-five patients were enrolled into this study. The 1-year PFS was 74.3 % and the overall RR was 85.7 %. The median PFS for all patients was 17.6 months (95 % confidence interval 15.5–∞), but the median OS was not reached, because 28 patients were still alive after a median follow-up time of 21.4 months. Haematological adverse events (grade 3 or higher) included neutropaenia (17.1 %), thrombocytopenia (14.3 %), and anaemia (5.7 %), while non-haematological adverse events (grade 3 or higher) included elevated aminotransferase (20.0 %), diarrhoea (14.3 %), and febrile neutropaenia (2.9 %). No interstitial lung disease or treatment-related deaths occurred. Combination chemotherapy with carboplatin, S-1, and gefitinib is efficacious and well tolerated as a first-line treatment in advanced NSCLC patients with activating EGFR mutations.

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Acknowledgments

The authors thank all the participants of this study.

Conflict of interest

The authors have declared no conflicts of interest.

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Authors and Affiliations

  1. Department of Internal Medicine, Kinki-Chuo Chest Medical Center, Osaka, Japan

    Akihiro Tamiya, Nobuhiko Saijo, Takeshi Nakatani, Shojiro Minomo, Taisuke Tsuji, Naoko Takeuchi & Naoki Omachi

  2. Department of Thoracic Malignancy, Osaka Prefectural Hospital Organization, Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Osaka, Japan

    Motohiro Tamiya, Takayuki Shiroyama, Kanako Kurata, Hidekazu. Suzuki, Norio Okamoto & Tomonori Hirashima

  3. Department of Thoracic Oncology, Kinki-Chuo Chest Medical Center, 1180 Nagasone-cho, Kita-Ku, Sakai, Osaka, 591-8555, Japan

    Kyoichi Okishio & Shinji Atagi

Authors
  1. Akihiro Tamiya
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  2. Motohiro Tamiya
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  3. Takayuki Shiroyama
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  4. Nobuhiko Saijo
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  5. Takeshi Nakatani
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  6. Shojiro Minomo
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  7. Taisuke Tsuji
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  8. Naoko Takeuchi
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  9. Naoki Omachi
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  10. Kanako Kurata
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  11. Hidekazu. Suzuki
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  12. Norio Okamoto
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  13. Kyoichi Okishio
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  14. Tomonori Hirashima
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  15. Shinji Atagi
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Corresponding author

Correspondence to Shinji Atagi.

Additional information

This trial is registered with the University Hospital Medical Information Network Clinical Trials Registry (Trial Number UMIN 000005503).

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Tamiya, A., Tamiya, M., Shiroyama, T. et al. Phase II trial of carboplatin, S-1, and gefitinib as first-line triplet chemotherapy for advanced non-small cell lung cancer patients with activating epidermal growth factor receptor mutations. Med Oncol 32, 40 (2015). https://doi.org/10.1007/s12032-014-0474-x

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  • DOI: https://doi.org/10.1007/s12032-014-0474-x

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