title: An escalating dose finding study of liposomal doxorubicin and vinorelbine for the treatment of refractory or resistant epithelial ovarian cancer.
abstract: BACKGROUND
  The aim of this study was to determine the maximum tolerated dose (MTD) of liposomal doxorubicin (LD)-vinorelbine (V) in patients with refractory or resistant ovarian cancer.
  
  
  METHODS
  Thirty patients were eligible. Seven levels were studied [LD 25-V20 (three patients enrolled); LD 30-V20 (three); LD 35-V20 (three); LD 20-V25 (three); LD 25-V25 (three); LD 30-V25 (10); LD 35-V25 (five)]. LD was given on day 1, while V was given on days 1 and 8 every 21 days. Cohorts of three patients were enrolled at each level, and another three patients were planned, if one dose-limiting toxicity (DLT) was registered.
  
  
  RESULTS
  DLT was observed in four patients: two febrile neutropenia, one grade 4 thrombocytopenia and one grade 3 palmar-plantar erythrodysesthesia (PPE) at level 7 (LD 35-V25). Thus, liposomal doxorubicin 30 mg/m(2) plus vinorelbine 25 mg/m(2) was the MTD. The most frequent toxicity was neutropenia. Fifteen patients (50%) experienced grade 3 neutropenia and 10 (33.3%) grade 4 neutropenia. Non-hematological toxicity was mild. Mucositis and PPE were the most frequent toxicities, but in most cases were grade 1. Out of 29 assessable patients, six (20.7%; 95% confidence interval 10%-39%) experienced an objective response, with one complete response.
  
  
  CONCLUSIONS
  In patients with refractory or resistant ovarian cancer, the recommended doses for the combination studied are liposomal doxorubicin 30 mg/m(2) (day 1) plus vinorelbine 25 mg/m(2) (day 1 and 8). Neutropenia is the most frequent toxicity, while non-hematological toxicity is mild. Substantial activity was recorded and a phase II study is justified.
authors.affiliation: Divisione di Oncologia Medica B, Istituto Nazionale Tumori, Napoli, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Tambaro
authors.forename: S
authors.initials: S
authors.lastname: Greggi
authors.forename: R V
authors.initials: RV
authors.lastname: Iaffaioli
authors.forename: A
authors.initials: A
authors.lastname: Rossi
authors.forename: C
authors.initials: C
authors.lastname: Pisano
authors.forename: L
authors.initials: L
authors.lastname: Manzione
authors.forename: E
authors.initials: E
authors.lastname: Ferrari
authors.forename: M
authors.initials: M
authors.lastname: Di Maio
authors.forename: F
authors.initials: F
authors.lastname: Iodice
authors.forename: G
authors.initials: G
authors.lastname: Casella
authors.forename: G
authors.initials: G
authors.lastname: Laurelli
authors.forename: S
authors.initials: S
authors.lastname: Pignata
mesh_terms: D000328:Adult; D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000473:pathology*; D005260:Female; D006801:Humans; D008081:Liposomes; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D014747:Vinblastine / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000077235:Vinorelbine
chemical_list: D000903:Antibiotics, Antineoplastic; D008081:Liposomes; D014747:Vinblastine; D004317:Doxorubicin; D000077235:Vinorelbine