Phase I/II study of a 3 weekly oral taxane (DJ-927) in patients with recurrent, advanced non-small cell lung cancer

Abstract

Introduction:: A phase I/II study was performed to assess the efficacy and toxicity of a new oral taxane in patients with recurrent, advanced Non-small Cell Lung Cancer. Patients and methods:: Patients who were treated with one prior, taxane free chemotherapy regimen, were eligible for this study. A single oral dose of DJ-927 (27 mg/m) was given every 3 weeks. In case of good tolerance, one dose escalation to 35 mg/m was allowed. Response and toxicity were measured and plasma pharmacokinetic analysis was performed during the first course. Results:: From October 2004 to September 2005, 36 patients gave informed consent and 34 received medication. The mean age was 58 years (range, 33-75 years). The majority of patients were pretreated with a combination of cisplatin and gemcitabine. Median interval between end of first treatment and the registration of this study was 7 months (range, 0.8-22 months). Twelve patients died on study of which eight due to disease progression. In four patients with preexisting cardiac disease, toxicity led to cardiac worsening and subsequent death. Grade 3 and 4 toxicities according to the National Cancer Institute Common Toxicity Criteria were neutropenia in 18 patients (53%), anemia in six patients (18%), nausea and fatigue in two patients (6%), febrile neutropenia and neurotoxicity in one patient (3%). The overall response rate for all patients was 5.6% (Confidence Interval [CI] 0.7-18.7%). The percentage of patients with stabilization for >6 weeks was 47%. The median time to progression was 97 days (CI: 47-167 days) and the median survival time was 120 days (CI: 68-222 days) for the ITT group. Since only a minority of patients (3) tolerated the higher drug dose we omitted this dose level because of hematological toxicity. Pharmacokinetic analysis showed that the median area under the curve (t = 0-168 hours) was 1752 ± 1355 ngr/ml/h and the half-life was 167 ± 77 hours. Conclusion:: When administered once every 3 weeks, this oral taxane formulation of DJ-927 was well-absorbed with a long terminal half-life of 167 ± 77 hour. DJ-927 has antitumor activity against Non-small Cell Lung Cancer when given as second-line monotherapy (overall response rate in 5.6%; CI 0.7-18.7%). Ten patients experienced SD for more than 8 weeks. Different types of dose administration (metronomic dosing) or combination with other cytotoxic agents should be considered in future studies. Copyright © 2008 by the International Association for the Study of Lung.