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

Abstract

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.

• Authors: 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
• Journal: Investigational new drugs (Invest New Drugs) Vol. 33 Issue 1 Pg. 201-14 (Feb 2015) ISSN: 1573-0646 [Electronic] United States
• PMID: 25344453 (Publication Type: Clinical Trial, Phase I, Clinical Trial, Phase II, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Organometallic Compounds
• Ruthenium Compounds
• imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III)
• Deoxycytidine
• Ruthenium
• Dimethyl Sulfoxide
• Gemcitabine

Topics

• Adult
• Aged
• Antineoplastic Combined Chemotherapy Protocols (adverse effects, pharmacokinetics, therapeutic use)
• Carcinoma, Non-Small-Cell Lung (drug therapy, metabolism)
• Deoxycytidine (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Dimethyl Sulfoxide (administration & dosage, adverse effects, analogs & derivatives, pharmacokinetics)
• Female
• Humans
• Lung Neoplasms (drug therapy, metabolism)
• Male
• Maximum Tolerated Dose
• Middle Aged
• Organometallic Compounds (administration & dosage, adverse effects, pharmacokinetics)
• Ruthenium (administration & dosage, adverse effects, blood, pharmacokinetics)
• Ruthenium Compounds
• Treatment Outcome
• Gemcitabine