title: Phase II study of liposomal doxorubicin in refractory ovarian cancer: antitumor activity and toxicity modification by liposomal encapsulation.
abstract: OBJECTIVE
  A phase II study of liposomal doxorubicin was conducted in patients with ovarian cancer who failed to respond to platinum- and paclitaxel-based regimens. Liposomal doxorubicin was selected as a result of its superior activity against ovarian cancer xenografts relative to free doxorubicin and activity in refractory ovarian cancer patients that was noted during the phase I study.
  
  
  METHODS
  Thirty-five consecutive patients were accrued in two institutions (22 in one and 13 in the other). All had progressive disease after either cisplatin or carboplatin and paclitaxel, or at least one platinum-based and one paclitaxel-based regimen. Patients received intravenous (I.V.) liposomal doxorubicin 50 mg/m2 every 3 weeks with a dose reduction to 40 mg/m2 in the event of grade 3 or 4 toxicities, or a lengthening of the interval to 4 weeks (and occasionally to 5 weeks) with persistence of grade 1 or 2 toxicities beyond 3 weeks.
  
  
  RESULTS
  Nine clinical responses (one complete response [CR], eight partial responses [PRs]) were observed in 35 patients (25.7%), with seven of these having been confirmed by two consecutive computed tomographic (CT) measurements. The median progression-free survival was 5.7 months with an overall survival of 1.5 to 24+ months (median, 11 months). Although 13 patients experienced grade 3 or 4 nonhematologic skin and mucosal toxicities (either hand-foot syndrome or stomatitis), with dose modifications, the treatment was very well tolerated. Nausea that was clearly attributable to the drug, hair loss, extravasation necrosis, or decreases in ejection fraction did not occur.
  
  
  CONCLUSIONS
  Liposomal doxorubicin has substantial activity against ovarian cancer refractory to platinum and paclitaxel. The responses achieved with liposomal doxorubicin were durable and maintained with minimal toxicity. This liposomal formulation should be evaluated further in combination with other drugs in less refractory patients.
authors.affiliation: Department of Radiology, University of Southern California-Norris Comprehensive Cancer Center, Los Angeles, USA. franco.muggia@ccmail.med.nyu.edu
authors.forename: F M
authors.initials: FM
authors.lastname: Muggia
authors.forename: J D
authors.initials: JD
authors.lastname: Hainsworth
authors.forename: S
authors.initials: S
authors.lastname: Jeffers
authors.forename: P
authors.initials: P
authors.lastname: Miller
authors.forename: S
authors.initials: S
authors.lastname: Groshen
authors.forename: M
authors.initials: M
authors.lastname: Tan
authors.forename: L
authors.initials: L
authors.lastname: Roman
authors.forename: B
authors.initials: B
authors.lastname: Uziely
authors.forename: L
authors.initials: L
authors.lastname: Muderspach
authors.forename: A
authors.initials: A
authors.lastname: Garcia
authors.forename: A
authors.initials: A
authors.lastname: Burnett
authors.forename: F A
authors.initials: FA
authors.lastname: Greco
authors.forename: C P
authors.initials: CP
authors.lastname: Morrow
authors.forename: L J
authors.initials: LJ
authors.lastname: Paradiso
authors.forename: L J
authors.initials: LJ
authors.lastname: Liang
mesh_terms: D000368:Aged; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use; D018394:CA-125 Antigen / Q000097:blood; D002945:Cisplatin / Q000627:therapeutic use; D018572:Disease-Free Survival; D004317:Doxorubicin / Q000009:adverse effects / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D004337:Drug Carriers; D019008:Drug Resistance, Neoplasm; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D008081:Liposomes; D008875:Middle Aged; D009503:Neutropenia / Q000139:chemically induced; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000276:immunology; D017239:Paclitaxel / Q000627:therapeutic use; D014456:Ulcer / Q000139:chemically induced
chemical_list: D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D018394:CA-125 Antigen; D004337:Drug Carriers; D008081:Liposomes; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin