A phase I and pharmacological study of amrubicin and topotecan in patients of small-cell lung cancer with relapsed or extensive-disease small-cell lung cancer

Takuo Shibayama, Katsuyuki Hotta, Nagio Takigawa, Atsuhiko Tada, Hiroshi Ueoka, Shingo Harita, Katsuyuki Kiura, Masahiro Tabata, Yoshihiko Segawa, Naoyuki Nogami, Shoichi Kuyama, Tetsu Shinkai, Mitsune Tanimoto

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Cisplatin-based chemotherapy is considered to be a standard treatment in patients with relapsed or extensive-disease (ED) small-cell lung cancer (SCLC), the survival benefit remains modest. Relapsed or ED-SCLC patients were enrolled. Topotecan and amrubicin were administered on Days 1-5 and on Days 3-5, respectively. Nine patients received a total of 24 cycles. Since all three patients experienced dose-limiting toxicity (grade 4 neutropenia lasting for more than 4 days, grade 3 febrile neutropenia, and grade 4 thrombocytopenia) at the third dose level (topotecan: 0.75 mg/m2, amrubicin 40 mg/m2), the maximum tolerated dose was determined to be this dose level. Objective response was observed in six patients (67%). The maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) of amrubicin increased in a dose-dependent manner. Amrubicin did not influence the pharmacokinetics of topotecan. The Cmax and AUC of amrubicin were correlated with the duration of grade 4 neutropenia. The mean Cmax of topotecan on day 2 in responders (22.9 ± 3.6) was significantly higher than that in non-responders (10.9 ± 0.4). This phase I study showed the safety and activity of two-drug combination of amrubicin and topotecan in patients with relapsed or ED-SCLC.

Original languageEnglish
Pages (from-to)189-195
Number of pages7
JournalLung Cancer
Volume53
Issue number2
DOIs
Publication statusPublished - Aug 1 2006

Keywords

  • Amrubicin
  • Lung cancer
  • Pharmacokinetics
  • Phase I trial
  • Topotecan

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine
  • Cancer Research

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