title: Clinical phase II study of pegylated liposomal doxorubicin as second-line treatment in disseminated melanoma.
abstract: BACKGROUND
  Stage IV melanoma has a poor prognosis with a median survival of 3-11 months from diagnosis of distant metastases. Response rates in first-line regimens range around 15-20%. Non-responders have a median survival around 6 months. Currently, no second-line treatment in advanced melanoma has been established.
  
  
  METHODS
  In a clinical phase II study we evaluated the efficacy of liposomal doxorubicin (Caelyx) in 30 patients (17 m, 13 f) with progressing metastatic melanoma who had failed a previous chemotherapy. Liposomal doxorubicin was given in an outpatient setting at a dose of 50 mg/m2 i.v. on d1, d22, d43 and d64, subsequently at 40 mg/m2 at d85 before first staging and in 4-week intervals thereafter. Treatment was very well tolerated with 100 cycles given in total. Response rate, survival time, time-to-progression and toxicity were assessed.
  
  
  RESULTS
  Erythrodysesthesia was the most severe toxicity in 6% at CTC grade 3. Liposomal doxorubicin was of limited clinical efficacy with 21 patients progressing within the first 12 weeks. However, 7 patients were treated 3-9 months and were stable for >90 days, achieving 5 SD, 1 PR and 1 CR. Median survival after initiation of second-line treatment was 214 days (95% CI: 151-304 days) with 7 patients surviving >300 and 5 patients >400 days.
  
  
  CONCLUSIONS
  Liposomal doxorubin as monotherapy is well tolerated but of limited clinical efficacy. Whether the survival benefit of a significant proportion of patients (20%) holds true in larger cohorts and whether the efficacy of liposomal doxorubicin can be improved by combinations without compromising the low toxicity profile needs further studies.
authors.affiliation: Skin Cancer Unit (German Cancer Research Center) at the Department of Dermatology, University Hospital Mannheim, Germany.
authors.forename: W
authors.initials: W
authors.lastname: Fink
authors.forename: C
authors.initials: C
authors.lastname: Zimpfer-Rechner
authors.forename: A
authors.initials: A
authors.lastname: Thoelke
authors.forename: R
authors.initials: R
authors.lastname: Figl
authors.forename: M
authors.initials: M
authors.lastname: Kaatz
authors.forename: S
authors.initials: S
authors.lastname: Ugurel
authors.forename: D
authors.initials: D
authors.lastname: Schadendorf
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D015897:Comorbidity; D004317:Doxorubicin / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D005260:Female; D005858:Germany / Q000453:epidemiology; D006402:Hematologic Diseases / Q000453:epidemiology; D006801:Humans; D008297:Male; D008545:Melanoma / Q000188:drug therapy* / Q000401:mortality* / Q000556:secondary; D008875:Middle Aged; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000401:mortality*; D010166:Palliative Care / Q000379:methods; D011092:Polyethylene Glycols; D018570:Risk Assessment / Q000379:methods*; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D011092:Polyethylene Glycols; D004317:Doxorubicin