title: Liposomal pegylated doxorubicin versus low-dose recombinant interferon Alfa-2a in the treatment of advanced classic Kaposi's sarcoma; retrospective analysis of three German centers.
abstract: BACKGROUND
  Classic Kaposi's sarcoma (KS) is a rare neoplasm, predominantly occurring in older subjects of Eastern Europe or Mediterranean descent. While single lesions may be treated by simple excision, laser therapy, cryotherapy, or intralesional therapy, advanced or disseminated disease requires systemic treatment. Several studies reported the effectiveness of pegylated liposomal doxorubicin (PLD) and low-dose recombinant interferon alfa-2a (IFNalpha) in the treatment of AIDS-associated KS.
  
  
  OBJECTIVE
  The aim of this retrospective analysis of three German centers was to compare the effectiveness and tolerability of PLD with IFNalpha in patients with advanced classic KS.
  
  
  METHODS
  Retrospective analysis of 18 Caucasian patients who had been treated for histologically proven classic KS, with either with PLD or IFNalpha was performed. Twelve patients received 20 mg/m2 of PLD monthly, and the number of cycles was adapted to the clinical response. Dose reduction or increased cycle length was conducted if toxicity intervened. In 6 patients, 3 million U of IFNalpha was injected subcutaneously 3 times a week. IFNalpha -therapy was adapted according to the clinical response.
  
  
  RESULTS
  In the 12 KS patients treated with PLD, complete response (CR) was achieved in 8 (67 percent), major response (MR) in 3 (25 percent), and minor response (mR) in 1 (8 percent). Stable disease (SD) or progression of disease (PD) was not observed. An initial response was noted after 4-16 weeks of treatment (mean 8.6 weeks), the mean cumulative dose of PLD was 571.5 mg/m2 (range, 40 to 1496 mg/m2), and the mean follow-up was 13 months. Neutropenia (33 percent) related to PLD was the most common adverse event (4/12). Vomiting occurred in 3 (25 percent) patients; none of these were severe. Six patients were treated with IFNalpha. MR was achieved in 1 (17 percent), mR in 4 (67 percent) and SD in 1 of 6 patients (17 percent), neither had CR or PD. An initial response was observed after 8-17 weeks of treatment (mean 12.7 weeks). Fever occurred in 4 patients (67 percent). Flu-like symptoms in 3 patients (50 percent) related to IFNalpha were the most common adverse events. Mean follow-up was 6.3 months. The differences in response to treatment between PLD and IFNalpha, in general, were significant with p < 0.05 (T-test for independent samples). Comparing weeks to respond and treatment efficiency data were significant with p < 0.001 (Fisher's exact): response to PLD was up to one-third faster than IFNalpha. Calculating different stages of response (MR, CR, etc.), PLD also was clearly superior (p = 0.018) to IFNalpha (Fisher's exact).
  
  
  CONCLUSIONS
  This retrospective analysis of patients with classic KS confirms the efficacy and safety of PLD. The benefits of PLD, including the monthly application, the high response even after previous treatments have failed, and the low rate of side effects even in elderly individuals, outweigh the risks. PLD is superior to IFNalpha and should be considered as an promising option in the treatment of advanced classic KS.
authors.affiliation: Department of Dermatology, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Kreuter
authors.forename: Heinrich
authors.initials: H
authors.lastname: Rasokat
authors.forename: Mariam
authors.initials: M
authors.lastname: Klouche
authors.forename: Stefan
authors.initials: S
authors.lastname: Esser
authors.forename: Armin
authors.initials: A
authors.lastname: Bader
authors.forename: Thilo
authors.initials: T
authors.lastname: Gambichler
authors.forename: Peter
authors.initials: P
authors.lastname: Altmeyer
authors.forename: Norbert H
authors.initials: NH
authors.lastname: Brockmeyer
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000627:therapeutic use*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D005858:Germany; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012514:Sarcoma, Kaposi / Q000188:drug therapy* / Q000473:pathology
chemical_list: D000903:Antibiotics, Antineoplastic; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; C506643:liposomal doxorubicin; D011092:Polyethylene Glycols; D004317:Doxorubicin