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Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902

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Abstract

Purpose

This phase II study evaluated the response rate (RR) and safety of combination therapy with carboplatin (CBDCA) and pemetrexed (PEM) in Japanese patients with non-squamous non-small cell lung cancer (non-sq NSCLC). Further, the relationship between therapy efficacy/toxicity and genetic polymorphisms associated with PEM metabolism was analyzed.

Methods

Forty-one patients received CBDCA at a dose targeting an area under the concentration–time curve of 5 mg/mL × min and PEM of 500 mg/m2 on day 1 every 3 weeks. Single-nucleotide polymorphisms of the thymidylate synthase (TYMS) coding gene, the variable number of tandem repeat (VNTR) in the TYMS, and the methylenetetrahydrofolate reductase (MTHFR) coding gene were analyzed.

Results

The overall RR was 36.6 %. Median progression-free survival and median survival time were 4.7 months [95 % confidence interval (CI) 3.9–5.6 months] and 16.2 months (95 % CI 6.1–26.2 months), respectively. Epidermal growth factor receptor gene mutations were detected in 6 patients (14.6 %). The VNTR in the TYMS significantly correlated with anemia (p = 0.047) and thrombocytopenia (p = 0.038).

Conclusions

This combination therapy was effective and tolerable in patients with advanced non-sq NSCLC. The VNTR in the TYMS appears to be a predictive factor for anemia and thrombocytopenia in patients treated with this regimen.

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Acknowledgments

We thank all the patients who participated in this study and also thank all institutions for recruiting patients.

Conflict of interest

Satoshi Oizumi received an honorarium from AstraZeneca and a grant from Eli Lilly. Others had no conflict of interest to declare.

Author information

Authors and Affiliations

  1. Department of Pulmonary Medicine, Fukushima Medical University School of Medicine, 1 Hikarigaoka, Fukushima, 960-1295, Japan

    Kenya Kanazawa, Hiroshi Yokouchi, Xintao Wang, Takashi Ishida & Mitsuru Munakata

  2. Clinical Oncology Center, Fukushima Medical University Hospital, 1 Hikarigaoka, Fukushima, 960-1295, Japan

    Takashi Ishida

  3. Department of Respiratory Medicine, National Hospital Organization Asahikawa Medical Center, 7-4048 Hanasaki-cho, Asahikawa, Hokkaido, 070-8644, Japan

    Yuka Fujita & Satoru Fujiuchi

  4. Center for Respiratory Disease, Japan Community Health Care Organization Hokkaido Hospital, 1-8-3-18 Nakanoshima, Toyohira-ku, Sapporo, Hokkaido, 062-8618, Japan

    Toshiyuki Harada

  5. Department of Respiratory Medicine, National Hospital Organization Hokkaido Cancer Center, 3-54, Kikusui 4-jo 2-chome, Shiroishi-ku, Sapporo, Hokkaido, 003-0804, Japan

    Masao Harada

  6. First Department of Medicine, Hokkaido P. W. F. A. C. Obihiro-Kosei General Hospital, 1-West-8-South-6, Obihiro, Hokkaido, 080-0016, Japan

    Kei Takamura

  7. First Department of Medicine, Hokkaido University School of Medicine, Kita 8, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-0808, Japan

    Satoshi Oizumi & Masaharu Nishimura

  8. Department of Medical Oncology, Hokkaido University Graduate School of Medicine, Kita 8, Nishi 5, Kita-ku, Sapporo, Hokkaido, 060-0808, Japan

    Ichiro Kinoshita & Hirotoshi Dosaka-Akita

  9. Department of Pulmonary Medicine, Saiseikai Fukushima General Hospital, 4-15 Sakuragi-cho, Fukushima, 960-8133, Japan

    Yutaka Katsuura

  10. Department of Respiratory Medicine, Hokkaido P. W. F. A. C. Sapporo-Kosei General Hospital, 5, Kita 3-jo Higashi 8-chome, Chuo-ku, Sapporo, Hokkaido, 003-0804, Japan

    Osamu Honjo

  11. Department of Medical Oncology and Respiratory Medicine, KKR Sapporo Medical Center, 3-40, Hiragishi 1-jo 6-chome, Toyohira-ku, Sapporo, Hokkaido, 062-0931, Japan

    Tetsuya Kojima & Hiroshi Isobe

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  1. Kenya Kanazawa
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  2. Hiroshi Yokouchi
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  3. Xintao Wang
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  4. Takashi Ishida
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  7. Toshiyuki Harada
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  8. Masao Harada
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  14. Tetsuya Kojima
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  15. Hirotoshi Dosaka-Akita
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  18. Masaharu Nishimura
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Hokkaido Lung Cancer Clinical Study Group

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Correspondence to Kenya Kanazawa.

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Kanazawa, K., Yokouchi, H., Wang, X. et al. Phase II trial of carboplatin and pemetrexed as first-line chemotherapy for non-squamous non-small cell lung cancer, and correlation between the efficacy/toxicity and genetic polymorphisms associated with pemetrexed metabolism: Hokkaido Lung Cancer Clinical Study Group Trial (HOT) 0902. Cancer Chemother Pharmacol 74, 1149–1157 (2014). https://doi.org/10.1007/s00280-014-2589-3

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