Phase I study of troxacitabine administered by continuous infusion in subjects with advanced solid malignancies

A. Jimeno, W. A. Messersmith, C. K. Lee, W. W. Ma, D. Laheru, R. C. Donehower, S. D. Baker, M. Hidalgo

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


Background: Troxacitabine is a novel L-nucleoside analogue. Preclinical studies showed improved activity with infusions of at least 3 days compared with bolus regimens, especially at concentrations >20 ng/ml. This phase I study tested the feasibility of achieving a troxacitabine steady-state concentration of 20 ng/ml for at least 72 h in patients with solid tumors. Patients and methods: Patients with solid tumors received troxacitabine as a progressively longer infusion on days 1-4 of a 28-day cycle. The initial length of infusion and infusion rate were 48 h and 3 mg/m2/day. Results: Twenty-one patients were treated at infusion lengths that increased from 48 to 72 h and then 96 h. The infusion rate was decreased from 3 to 1.88 mg/m2day due to toxicity. Dose-limiting toxicities consisted of grade 4 neutropenia (three) and grade 3 constipation (one). The maximum tolerated dose of continuous infusion troxacitabine in patients with solid tumors is 7.5 mg/m2 administered over 96 h. This dose level resulted in steady-state drug concentration of at least 20 ng/ml for 72 h. Conclusions: Administration of troxacitabine by continuous infusion achieved the prospectively defined target plasma concentration. Pharmacokinetics (PK) modeling coupled with real-time PK assessment was an efficient approach to conduct hypothesis-driven phase I trials.

Original languageEnglish (US)
Pages (from-to)374-379
Number of pages6
JournalAnnals of Oncology
Issue number2
StatePublished - Feb 2008


  • Continuous infusion
  • PK modeling
  • Troxacitabine

ASJC Scopus subject areas

  • Hematology
  • Oncology


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