title: Pegylated liposomal doxorubicin and cyclophosphamide in early recurrent ovarian carcinoma: phase I dose-finding study.
abstract: OBJECTIVE
  This single-arm phase I dose-escalation study determines the optimal dose of the non-platinum treatment pegylated liposomal doxorubicin (PLD) plus cyclophosphamide (CPM) every 4 weeks in early recurrent ovarian carcinoma.
  
  
  METHODS
  Twenty-one women with ovarian carcinoma relapsing within 12 months of first-line surgery and platinum-taxane chemotherapy received escalating doses of PLD (35-45 mg/m(2)) and CPM (500-600 mg/m(2)) every 4 weeks for at least two cycles. Primary objective was assessment of maximum-tolerated dose (MTD) over the first two cycles. Secondary objectives were to assess safety over 2 cycles, efficacy evaluated every two cycles (response evaluation criteria in solid tumours criteria) and overall survival (OS).
  
  
  RESULTS
  The PLD-CPM MTD was 40/600 mg/m(2) with 2/3 patients treated at 45/500 mg/m(2), showing DLTs with Grade 3/4 oesophagitis, thrombopenia/neutropenia, leucopoenia, and Grade 3 stomatitis/asthenia during the first cycle of treatment. Four severe toxicities were reported by three patients during the two first cycles, namely Grade 4 anaemia, and Grade 3 stomatitis. The most common treatment-related toxicities were anaemia (71.4 %), nausea (61.9 %), neutropenia (57.1 %), asthenia (52.4 %), leucopoenia (47.6 %), stomatitis (42.9 %), skin (28.6 %) and palmar-plantar-erythrodysesthesia (19 %). No treatment-related deaths were reported. The overall response rate (complete and partial) was 31 %, and median OS was 8.2 months [95 % CI (3.3-13.2)].
  
  
  CONCLUSIONS
  The combination of PLD and CPM is feasible and may be considered particularly in cases where platinum-based treatment is not suitable. The recommended doses for a phase II trial are PLD 40 mg/m(2) plus CPM 600 mg/m(2) every 4 weeks.
authors.affiliation: Department of Medical Oncology, Institut Bergonié, 229 Cours de l'Argonne, 33076, Bordeaux, France, a.floquet@bordeaux.unicancer.fr.
authors.forename: Anne
authors.initials: A
authors.lastname: Floquet
authors.forename: Adélaïde
authors.initials: A
authors.lastname: Doussau
authors.forename: Véronique
authors.initials: V
authors.lastname: Brouste
authors.forename: Laurent
authors.initials: L
authors.lastname: Cany
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Dutin
authors.forename: Simone
authors.initials: S
authors.lastname: Mathoulin-Pélissier
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D003520:Cyclophosphamide / Q000008:administration & dosage / Q000009:adverse effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy*; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000401:mortality; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000009:adverse effects
chemical_list: C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin; D003520:Cyclophosphamide