title: Gemcitabine and pegylated liposomal doxorubicin alternating with cisplatin plus cyclophosphamide in platinum refractory/resistant, paclitaxel-pretreated, ovarian carcinoma.
abstract: OBJECTIVE
  This phase II study conducted to investigate the efficacy and toxicity of the combination of gemcitabine (GEM) and pegylated liposomal doxorubicin (LDOX) alternating with cisplatin (CDDP) and cyclophosphamide (CTX) in platinum-resistant/refractory, paclitaxel pretreated epithelial ovarian cancer (EOC).
  
  
  METHODS
  Forty-eight patients with CDDP-resistant/refractory and paclitaxel pretreated patients were treated with 8 cycles of GEM 800 mg/m2 days 1 and 8 and LDOX 30 mg/m2 day 1, alternating with CDDP 60 mg/m2 and CTX 600 mg/m2 every 3 weeks.
  
  
  RESULTS
  Objective responses were observed in 37.5% of patients (4 complete and 11 partial responses) with measurable disease (n=40). CA125 response occurred in 30 (71.4%) of patients with elevated CA125 (n=42). After a median follow-up of 23 months, the median progression-free survival (PFS) was 6.9 months (95% confidence interval, CI: 5.2-8.5), while the median overall survival (OS) was 18.2 months (95% CI: 12.7-23.6). A progression-free interval (PFI) of 0-3 months was associated with lower objective responses (10% versus 46.6%, p=0.06). Chemotherapy was well tolerated. The most frequent toxicities were myelosuppression, neurotoxicity, nephrotoxicity, nausea/vomiting, fatigue and palmar-plantar erythrodysesthesia (PPE). Overall 31 (65%) patients received G-CSF and 13 (27%) antibiotics because of neutropenia and/or febrile neutropenia.
  
  
  CONCLUSIONS
  This alternating combination chemotherapy is feasible for patients with platinum-resistant EOC and is associated with encouraging outcomes and a favorable toxicity profile.
authors.affiliation: 2nd Department of Internal Medicine, Propaedeutic, Oncology Section, University of Athens, Attikon University Hospital, Haidari, 1 Rimini, Athens, Greece. pectasid@otenet.gr
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Pectasides
authors.forename: Nicolaos
authors.initials: N
authors.lastname: Xiros
authors.forename: George
authors.initials: G
authors.lastname: Papaxoinis
authors.forename: Gerasimos
authors.initials: G
authors.lastname: Aravantinos
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sykiotis
authors.forename: Erini
authors.initials: E
authors.lastname: Pectasides
authors.forename: Amanda
authors.initials: A
authors.lastname: Psyrri
authors.forename: Anna
authors.initials: A
authors.lastname: Koumarianou
authors.forename: Asimina
authors.initials: A
authors.lastname: Gaglia
authors.forename: Panayiotis
authors.initials: P
authors.lastname: Gouveris
authors.forename: Theofanis
authors.initials: T
authors.lastname: Economopoulos
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects; D016190:Carboplatin / Q000494:pharmacology; D002945:Cisplatin / Q000008:administration & dosage / Q000009:adverse effects; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D017239:Paclitaxel / Q000008:administration & dosage; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects; D000093542:Gemcitabine
chemical_list: C506643:liposomal doxorubicin; D003841:Deoxycytidine; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D002945:Cisplatin; D000093542:Gemcitabine