Investigational New Drugs

, Volume 33, Issue 1, pp 201–214 | Cite as

Phase I/II study with ruthenium compound NAMI-A and gemcitabine in patients with non-small cell lung cancer after first line therapy

  • Suzanne Leijen
  • Sjaak A. Burgers
  • Paul Baas
  • Dick Pluim
  • Matthijs Tibben
  • Erik van Werkhoven
  • Enzo Alessio
  • Gianni Sava
  • Jos H. Beijnen
  • Jan H. M. Schellens
PHASE I STUDIES

Summary

Background This phase I/II study determined the maximal tolerable dose, dose limiting toxicities, antitumor activity, the pharmacokinetics and pharmacodynamics of ruthenium compound NAMI-A in combination with gemcitabine in Non-Small Cell Lung Cancer patients after first line treatment. Methods Initial dose escalation of NAMI-A was performed in a 28 day cycle: NAMI-A as a 3 h infusion through a port-a-cath at a starting dose of 300 mg/m2 at day 1, 8 and 15, in combination with gemcitabine 1,000 mg/m2 at days 2, 9 and 16. Subsequently, dose escalation of NAMI-A in a 21 day schedule was explored. At the maximal tolerable dose level of this schedule an expansion group was enrolled of which 15 patients were evaluable for response. Results Due to frequent neutropenic dose interruptions in the third week, the 28 day schedule was amended into a 21 day schedule. The maximal tolerable dose was 300 and 450 mg/m2 of NAMI-A (21 day schedule). Main adverse events consisted of neutropenia, anemia, elevated liver enzymes, transient creatinine elevation, nausea, vomiting, constipation, diarrhea, fatigue, and renal toxicity. Conclusion NAMI-A administered in combination with gemcitabine is only moderately tolerated and less active in NSCLC patients after first line treatment than gemcitabine alone.

Keywords

NAMI-A Ruthenium Phase I Phase II Clinical study Gemcitabine Non-small cell lung cancer 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Suzanne Leijen
    • 1
  • Sjaak A. Burgers
    • 2
  • Paul Baas
    • 2
    • 3
  • Dick Pluim
    • 1
  • Matthijs Tibben
    • 4
  • Erik van Werkhoven
    • 5
  • Enzo Alessio
    • 6
  • Gianni Sava
    • 7
    • 8
  • Jos H. Beijnen
    • 4
  • Jan H. M. Schellens
    • 1
    • 9
  1. 1.Department of Clinical Pharmacology, The Netherlands Cancer InstituteAmsterdamThe Netherlands
  2. 2.Department of Thoracic Oncology, The Netherlands Cancer InstituteAmsterdamThe Netherlands
  3. 3.Department of Thoracic Oncology, Amsterdam Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Pharmacy and Pharmacology, Slotervaart HospitalAmsterdamThe Netherlands
  5. 5.Biometrics Department, The Netherlands Cancer InstituteAmsterdamThe Netherlands
  6. 6.University of Trieste, Department of Chemical and Pharmaceutical SciencesTriesteItaly
  7. 7.Callerio Foundation OnlusTriesteItaly
  8. 8.Department of Life SciencesUniversity of TriesteTriesteItaly
  9. 9.Department of Pharmaceutical SciencesUtrecht UniversityUtrechtThe Netherlands

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