title: First-line chemotherapy with liposomal doxorubicin plus cisplatin for patients with advanced malignant pleural mesothelioma: phase II trial.
abstract: BACKGROUND
  Chemotherapy based on platinum is the standard treatment for unresectable malignant pleural mesothelioma (MPM). Liposomal doxorubicin (LD) consists of pegylated phospholipid vesicles that encapsulate doxorubicin-enhancing liposome deposition in the tumour. We evaluated the toxicity profile and anti-tumour activity of cisplatin plus LD in untreated patients with MPM, as well as (99m)Tc-LD distribution in MPM lesions after chemotherapy administration.
  
  
  METHODS
  A total of 38 patients with non-resectable MPM received LD 40 mg m(-2) and cisplatin 60 mg m(-2) every 21 days. Gamma camera images of (99m)Tc-LD were acquired to evaluate LD accumulation in measurable tumour tissue. The study was registered in Clinical Trials (NCT00886028).
  
  
  RESULTS
  In all, 72% of patients were stage III and 28% were stage IV. Eighty four percent and 16% have high and low risk acording EORTC respectively. The median time to progression was 4.6 months (95% confidence interval (95% CI: 3.4-5.9 months), and median overall survival (OS) was 19.6 months (15.2-37.2 months). Patients that responded to chemotherapy treatment had better survival than patients who did not. Functional physical scales, dysnea, cough, and chest/arm pain demonstrated improvement. The accumulation ratio of LD in tumour and soft tissues vs liver was 0.78±0.16 and 0.29±0.09, respectively. After 1 h of administration, LD uptake in tumour tissue was higher than in soft tissue (P< 0.001).
  
  
  CONCLUSIONS
  The combination of LD and cisplatin results in an active therapeutic regimen for unresectable MPM, with an acceptable toxicity profile and improvement in quality of life. (99m)Tc-LD showed higher levels of tumour uptake as compared with surrounding tissues.
authors.affiliation: Clinica de Tumores Torácicos, San Fernando #22, Colonia Sección XVI, Tlalpan, México City 14080, México. ogar@servidor.unam.mx
authors.forename: Ó
authors.initials: Ó
authors.lastname: Arrieta
authors.forename: L A
authors.initials: LA
authors.lastname: Medina
authors.forename: E
authors.initials: E
authors.lastname: Estrada-Lobato
authors.forename: N
authors.initials: N
authors.lastname: Hernández-Pedro
authors.forename: G
authors.initials: G
authors.lastname: Villanueva-Rodríguez
authors.forename: L
authors.initials: L
authors.lastname: Martínez-Barrera
authors.forename: E O
authors.initials: EO
authors.lastname: Macedo
authors.forename: V
authors.initials: V
authors.lastname: López-Rodríguez
authors.forename: D
authors.initials: D
authors.lastname: Motola-Kuba
authors.forename: J F
authors.initials: JF
authors.lastname: Corona-Cruz
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000493:pharmacokinetics / Q000627:therapeutic use*; D002945:Cisplatin / Q000008:administration & dosage; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008081:Liposomes; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011788:Quality of Life; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D008081:Liposomes; D004317:Doxorubicin; D002945:Cisplatin