title: A pilot study on safety and pharmacokinetics of infliximab for the cancer anorexia/weight loss syndrome in non-small-cell lung cancer patients.
abstract: BACKGROUND
  Weight loss predicts a poor prognosis for patients with non-small-cell lung cancer. Tumor necrosis factor alpha (TNFalpha) is a mediator of this weight loss, yet no studies have tested infliximab, an IgG monoclonal antibody that blocks the binding of TNFalpha to its p55 and p75 receptors, for this indication. The safety and pharmacokinetics of infliximab in combination with docetaxel, a commonly used chemotherapy agent for non-small-cell lung cancer, were explored in this pilot study.
  
  
  RESULTS
  Four patients with metastatic non-small-cell lung cancer were treated initially with infliximab 5 mg/kg per day intravenously once a week on weeks 1, 3 and 5, and docetaxel 36 mg/m2 per day intravenously once a week on weeks 1, 2, 3, 4, 5 and 6 of an 8-week treatment cycle. Therapy was well tolerated with no grade 4 or 5 adverse events. Maximal serum concentrations of infliximab at 1, 3 and 5 weeks were (mean+/-SD) 108+/-11, 135+/-19, and 139+/-6 microg/ml, respectively, and appeared similar to historical concentrations from non-cancer patients not receiving concomitant chemotherapy (144+/-68 microg/ml). One patient manifested weight stability. One patient manifested a partial tumor response, one stable disease, and two disease progression. Median survival within the cohort was 203 days (range 111 to 324 days).
  
  
  CONCLUSIONS
  The above combination appears safe, and docetaxel does not appear to increase serum concentrations of infliximab. A larger study testing the role of this combination for weight loss in non-small-cell lung cancer patients is ongoing and utilizes the doses described above.
authors.affiliation: Division of Medical Oncology, Department of Oncology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905, USA. jatoi.aminah@mayo.edu
authors.forename: Aminah
authors.initials: A
authors.lastname: Jatoi
authors.forename: James R
authors.initials: JR
authors.lastname: Jett
authors.forename: Jeff
authors.initials: J
authors.lastname: Sloan
authors.forename: Paul
authors.initials: P
authors.lastname: Novotny
authors.forename: Joyce
authors.initials: J
authors.lastname: Ford
authors.forename: Uma
authors.initials: U
authors.lastname: Prabhakar
authors.forename: Charles L
authors.initials: CL
authors.lastname: Loprinzi
mesh_terms: D000368:Aged; D000855:Anorexia / Q000517:prevention & control*; D000911:Antibodies, Monoclonal / Q000493:pharmacokinetics*; D000972:Antineoplastic Agents, Phytogenic / Q000493:pharmacokinetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D000077143:Docetaxel; D005260:Female; D005765:Gastrointestinal Agents / Q000493:pharmacokinetics*; D006801:Humans; D000069285:Infliximab; D008175:Lung Neoplasms / Q000188:drug therapy*; D008297:Male; D010865:Pilot Projects; D043823:Taxoids / Q000493:pharmacokinetics*; D015431:Weight Loss / Q000187:drug effects*
chemical_list: D000911:Antibodies, Monoclonal; D000972:Antineoplastic Agents, Phytogenic; D005765:Gastrointestinal Agents; D043823:Taxoids; D000077143:Docetaxel; D000069285:Infliximab