Cancer Chemotherapy and Pharmacology

, Volume 62, Issue 1, pp 43–49

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

  • Nanae Tomonaga
  • Yoichi Nakamura
  • Hiroshi Soda
  • Seiji Nagashima
  • Hirofumi Nakano
  • Akitoshi Kinoshita
  • Masaaki Fukuda
  • Minoru Fukuda
  • Hiroshi Takatani
  • Yoshifumi Soejima
  • Mikio Oka
  • Shigeru Kohno
  • the Nagasaki Thoracic Oncology Group
Original Article

DOI: 10.1007/s00280-007-0571-z

Cite this article as:
Tomonaga, N., Nakamura, Y., Soda, H. et al. Cancer Chemother Pharmacol (2008) 62: 43. doi:10.1007/s00280-007-0571-z
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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.

Keywords

Non-small cell lung cancer Chemotherapy Vinorelbine Irinotecan Phlebitis Clobetasol ointment 

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Nanae Tomonaga
    • 1
  • Yoichi Nakamura
    • 2
  • Hiroshi Soda
    • 2
  • Seiji Nagashima
    • 1
  • Hirofumi Nakano
    • 2
  • Akitoshi Kinoshita
    • 3
  • Masaaki Fukuda
    • 4
  • Minoru Fukuda
    • 5
  • Hiroshi Takatani
    • 6
  • Yoshifumi Soejima
    • 7
  • Mikio Oka
    • 5
  • Shigeru Kohno
    • 2
  • the Nagasaki Thoracic Oncology Group
  1. 1.Department of Internal MedicineSasebo General HospitalNagasakiJapan
  2. 2.Second Department of Internal MedicineNagasaki University School of MedicineNagasakiJapan
  3. 3.National Hospital Organization, Nagasaki Medical CenterNagasakiJapan
  4. 4.Japanese Red-Cross Nagasaki Atomic Bomb HospitalNagasakiJapan
  5. 5.Division of Respiratory Diseases, Department of MedicineKawasaki Medical SchoolOkayamaJapan
  6. 6.Nagasaki Municipal HospitalNagasakiJapan
  7. 7.National Hospital Organization, Ureshino Medical CenterSagaJapan