title: Topotecan and pegylated liposomal doxorubicin combination as palliative treatment in patients with pretreated advanced malignant pleural mesothelioma.
abstract: BACKGROUND
  Malignant pleural mesothelioma (MPM) is an aggressive disease with poor or modest responses to chemotherapy and dismal prognosis. In most of the cases the scope of the treatment is only palliative. In the current study, the combination of i.v. topotecan and pegylated liposomal doxorubicin (PLD) in advanced multi-treated MPM was tested. Primary objective was palliation of the symptoms, with the secondary ones being the establishment of the regimen's safety and efficacy.
  
  
  METHODS
  Nine patients were enrolled (7 males/2 females, median age 57.5 years, ECOG performance status ≤ 2), having progressed after 2 or 3 lines of chemotherapy including pemetrexed and cisplatin. Main symptoms were dyspnea, cough, chest pain, fatigue, and anorexia. The treatment included topotecan 1.2 mg/m2 i.v. on Days 1 - 3 and PLD 40 mg/m2 on Day 4, every 28 days. The patients received 4 - 8 chemotherapy cycles (median 5.8).
  
  
  RESULTS
  In all cases, symptoms were significantly improved after the 2nd treatment cycle. Respiratory function tests showed considerable enhancement, while cough and pain were drastically reduced. All patients had objective clinical benefit, 1 patient achieving partial response and 8 stable disease. Median time to progression and overall survival was 7 and 9 months, respectively. The chosen dose of the topotecan/ PLD combination was well-tolerated with no Grade 3/4 toxicities. Quality of life, as it was evaluated by the QLQ-C30 and QLQLC13 questionnaires, had improved scores especially the ones referring symptomatology.
  
  
  CONCLUSIONS
  The current study shows a significant palliative effect of the topotecan/ PLD combination in pretreated patients with advanced MPM.
authors.affiliation: Department of Pharmcology, University of Athens, Athens, Greece. dtrafal@med.uoa.gr
authors.forename: Dimitrios T
authors.initials: DT
authors.lastname: Trafalis
authors.forename: Constantinos
authors.initials: C
authors.lastname: Alifieris
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Krikelis
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Tzogkas
authors.forename: George P
authors.initials: GP
authors.lastname: Stathopoulos
authors.forename: Athanassios E
authors.initials: AE
authors.lastname: Athanassiou
authors.forename: Nikolaos M
authors.initials: NM
authors.lastname: Sitaras
mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008654:Mesothelioma / Q000188:drug therapy* / Q000401:mortality; D008875:Middle Aged; D010166:Palliative Care; D010997:Pleural Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D019772:Topotecan / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D019772:Topotecan; D004317:Doxorubicin