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/m(2) at day 1, 8 and 15, in combination with gemcitabine 1,000 mg/m(2) 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/m(2) 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.
