title: Inhaled lipid cisplatin (ILC) in the treatment of patients with relapsed/progressive osteosarcoma metastatic to the lung.
abstract: BACKGROUND
  Osteosarcoma treatment failure is most often from the inability to control metastatic disease in the lungs. Encapsulating cisplatin within lipid complexes and delivering the agent via inhalation targets lung metastases with minimal systemic exposure. An open-label, phase Ib/IIa study was performed to characterize the safety and efficacy of inhaled lipid cisplatin (ILC) in recurrent osteosarcoma patients who only had pulmonary metastases.
  
  
  METHODS
  ILC was administered via nebulizer every 2 weeks (=1 cycle). Response was evaluated radiographically every 2 cycles. Cisplatin levels were measured in patients. When possible, metastasectomy was undertaken in patients after 2 cycles.
  
  
  RESULTS
  Nineteen patients were treated. No patients experienced hematologic toxicity, nephrotoxicity or ototoxicity. Nausea/vomiting (≥grade 3) was attributed to study drug in one patient. Respiratory symptoms were observed in 13/19 patients with only one patient experiencing a ≥grade 3 respiratory symptom (not related to study drug). Systemic cisplatin exposure was minimal. Eleven patients had bulky disease, and all progressed prior to cycle 7. Eight patients had all lesions ≤2 cm. One patient had a sustained partial response. An additional two patients had stable disease after 2 cycles, underwent metastasectomy, and remained free from pulmonary recurrence 1 year after initiation of therapy.
  
  
  CONCLUSIONS
  ILC is well tolerated in heavily treated osteosarcoma patients and did not appear to have the typical toxicities associated with intravenous cisplatin. Three of eight patients with less bulky disease had sustained benefit. Further study of ILC is warranted.
authors.affiliation: Department of Pediatrics, Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA. choua@mskcc.org
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Chou
authors.forename: Renu
authors.initials: R
authors.lastname: Gupta
authors.forename: Moshe D
authors.initials: MD
authors.lastname: Bell
authors.forename: Kathleen O'Day
authors.initials: KO
authors.lastname: Riewe
authors.forename: Paul A
authors.initials: PA
authors.lastname: Meyers
authors.forename: Richard
authors.initials: R
authors.lastname: Gorlick
mesh_terms: D000280:Administration, Inhalation; D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002626:Chemistry, Pharmaceutical; D002945:Cisplatin / Q000008:administration & dosage* / Q000009:adverse effects; D005260:Female; D006801:Humans; D008055:Lipids / Q000008:administration & dosage; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary; D008297:Male; D012516:Osteosarcoma / Q000188:drug therapy* / Q000556:secondary; D055815:Young Adult
chemical_list: D000970:Antineoplastic Agents; D008055:Lipids; D002945:Cisplatin