title: 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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Clinical Pharmacology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
authors.forename: Suzanne
authors.initials: S
authors.lastname: Leijen
authors.forename: Sjaak A
authors.initials: SA
authors.lastname: Burgers
authors.forename: Paul
authors.initials: P
authors.lastname: Baas
authors.forename: Dick
authors.initials: D
authors.lastname: Pluim
authors.forename: Matthijs
authors.initials: M
authors.lastname: Tibben
authors.forename: Erik
authors.initials: E
authors.lastname: van Werkhoven
authors.forename: Enzo
authors.initials: E
authors.lastname: Alessio
authors.forename: Gianni
authors.initials: G
authors.lastname: Sava
authors.forename: Jos H
authors.initials: JH
authors.lastname: Beijnen
authors.forename: Jan H M
authors.initials: JH
authors.lastname: Schellens
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives / Q000493:pharmacokinetics; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D012428:Ruthenium / Q000008:administration & dosage / Q000009:adverse effects / Q000097:blood / Q000493:pharmacokinetics; D017975:Ruthenium Compounds; D016896:Treatment Outcome; D000093542:Gemcitabine
chemical_list: D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D003841:Deoxycytidine; D012428:Ruthenium; D004121:Dimethyl Sulfoxide; D000093542:Gemcitabine