Combination of nedaplatin and vindesine for treatment of relapsed or refratory non-small-cell lung cancer

Nagio Takigawa, Yoshihiko Segawa, Hiroshi Ueoka, Katsuyuki Kiura, Masahiro Tabata, Takuo Shibayama, Ichiro Takata, Hiroaki Miyamoto, Kenji Eguchi, Mine Harada

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14 Citations (Scopus)

Abstract

Purpose: A phase II study of nedaplatin and vindesine was conducted to evaluate their efficacy and safety for treatment of relapsed or refractory non-small-cell lung cancer (NSCLC). Methods: Between August 1996 and September 1998, 48 patients who had previously received chemotherapy, thoracic radiotherapy, and/or surgery were enrolled in the study. Patients were required to have an Eastern Cooperative Oncology Group performance status of 0 to 2 and an age between 20 and 79 years. Treatment consisted of nedaplatin (80 mg/m2, day 1) and vindesine (3 mg/m2, days 1 and 8) every 3 to 4 weeks. Results: Of 48 patients, 7 (14.6%) exhibited an objective response. Four (50%) of eight chemotherapy-naive patients had a partial response. However, of the 40 patients who had received prior chemotherapy, a partial response was observed in only 3 (7.5%). At a median follow-up time of 85.1 weeks, the median survival time was 43.6 weeks (95% confidence interval 34.4-52.7) for patients who had received chemotherapy, with a survival rate of 40% at 1 year. Grade 3 or 4 neutropenia occurred in 43 of 48 patients (90%), and neutropenic fever was observed in 3 of the 43 patients, one of whom died of sepsis. Pharmacokinetic and pharmacodynamic analyses of platinum were performed in 43 patients during the first cycle of chemotherapy. Percent reduction in absolute neutrophil count was correlated not only with the area under the plasma ultrafilterable platinum concentration versus time curve (r = 0.41; P = 0.007) but also with the duration of ultrafilterable platinum concentration above 1 μg/ml (r = 0.41, P = 0.007). Patients with progressive disease exhibited a shorter duration of ultrafilterable platinum concentration over 1 μg/ml (P = 0.046) than those with other responses. Conclusion: A combination of nedaplatin and vindesine was unsatisfactory as second-line chemotherapy for NSCLC, although the combination was well tolerated. The duration of ultrafilterable platinum concentration above 1 μg/ml was an important pharmacokinetic parameter for predicting both chemotherapy-induced neutropenia and treatment outcome.

Original languageEnglish
Pages (from-to)272-278
Number of pages7
JournalCancer Chemotherapy and Pharmacology
Volume46
Issue number4
DOIs
Publication statusPublished - 2000

Keywords

  • Nedaplatin
  • Non-small-cell lung cancer
  • Pharmacodynamics
  • Pharmacokinetics
  • Vindesine

ASJC Scopus subject areas

  • Oncology
  • Toxicology
  • Pharmacology
  • Cancer Research
  • Pharmacology (medical)

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