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Phase I study of vinorelbine and irinotecan in previously untreated patients with advanced non-small cell lung cancer

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Abstract

Introduction

Vinorelbine alone and irinotecan alone have been shown to have efficacy against non-small cell lung cancer (NSCLC); each drug has different mechanisms of action. A phase I study using a combination of vinorelbine and irinotecan as first-line treatment for advanced NSCLC was done to determine the maximum tolerated dose (MTD) and the dose-limiting toxicity (DLT).

Methods

Previously untreated patients (≤75 years old) with Stage IIIB or IV NSCLC were enrolled. Based on a 4-week cycle, vinorelbine was given on days 1 and 8, and irinotecan was given on days 1, 8, and 15 intravenously. To prevent an injection site reaction to vinorelbine, the site was treated with topical clobetasol ointment, and the patients were given intravenous dexamethasone prior to vinorelbine treatment. DLT was defined as grade 4 neutropenia lasting ≥4 days or febrile neutropenia, grade 4 thrombocytopenia, ≥grade 3 non-hematological toxicities, or the need to cancel drug administration on both days 8 and 15.

Results

A total of 23 patients were enrolled. DLT was observed in 1 of 6 patients at level 3 (20 mg/m2 vinorelbine, 50 mg/m2 irinotecan), in 2 of 3 at level 4 (25 mg/m2, 50 mg/m2), and in 2 of 5 at modified level 4 (20, 60 mg/m2). Level 4 and modified level 4 were considered to be the MTD; dose level 3 was therefore recommended. DLTs included liver dysfunction, pneumonitis, colitis, and arrhythmia. Injection site reactions were mild. Hematological and non-hematological toxicities were mild and easily controlled.

Conclusion

Use of 20 mg/m2 vinorelbine on days 1 and 8 followed by 50 mg/m2 irinotecan on days 1, 8, and 15 every 4 weeks warrants a phase II study.

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Authors and Affiliations

  1. Department of Internal Medicine, Sasebo General Hospital, Nagasaki, Japan

    Nanae Tomonaga & Seiji Nagashima

  2. Second Department of Internal Medicine, Nagasaki University School of Medicine, 1-7-1 Sakamoto, Nagasaki, 852-8501, Japan

    Yoichi Nakamura, Hiroshi Soda, Hirofumi Nakano & Shigeru Kohno

  3. National Hospital Organization, Nagasaki Medical Center, Nagasaki, Japan

    Akitoshi Kinoshita

  4. Japanese Red-Cross Nagasaki Atomic Bomb Hospital, Nagasaki, Japan

    Masaaki Fukuda

  5. Division of Respiratory Diseases, Department of Medicine, Kawasaki Medical School, Okayama, Japan

    Minoru Fukuda & Mikio Oka

  6. Nagasaki Municipal Hospital, Nagasaki, Japan

    Hiroshi Takatani

  7. National Hospital Organization, Ureshino Medical Center, Saga, Japan

    Yoshifumi Soejima

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  1. Nanae Tomonaga
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  2. Yoichi Nakamura
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  3. Hiroshi Soda
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the Nagasaki Thoracic Oncology Group

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Correspondence to Yoichi Nakamura.

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Tomonaga, N., Nakamura, Y., Soda, H. et al. Phase I study of vinorelbine and irinotecan in previously untreated patients with advanced non-small cell lung cancer. Cancer Chemother Pharmacol 62, 43–49 (2008). https://doi.org/10.1007/s00280-007-0571-z

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  • DOI: https://doi.org/10.1007/s00280-007-0571-z

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