Clinical Phase II Study of Pegylated Liposomal Doxorubicin as Second-Line Treatment in Disseminated Melanoma

Abstract

Background: Stage IV melanoma has a poor prognosis witha median survival of 3-11 months from diagnosis of distantmetastases. Response rates in first-line regimens rangearound 15-20%. Non-responders have a median survivalaround 6 months. Currently, no second-line treatment in advancedmelanoma has been established. Patients and Methods:In a clinical phase II study we evaluated the efficacy ofliposomal doxorubicin (Caelyx?) in 30 patients (17 m, 13 f)with progressing metastatic melanoma who had failed aprevious chemotherapy. Liposomal doxorubicin was givenin 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 beforefirst staging and in 4-week intervals thereafter. Treatmentwas very well tolerated with 100 cycles given in total. Responserate, survival time, time-to-progression and toxicitywere assessed. Results: Erythrodysesthesia was the mostsevere toxicity in 6% at CTC grade 3. Liposomal doxorubicinwas of limited clinical efficacy with 21 patients progressingwithin the first 12 weeks. However, 7 patients were treated3-9 months and were stable for >90 days, achieving 5 SD,1 PR and 1 CR. Median survival after initiation of second-linetreatment was 214 days (95% CI: 151-304 days) with 7 patientssurviving >300 and 5 patients >400 days. Conclusions:Liposomal doxorubin as monotherapy is well tolerated butof limited clinical efficacy. Whether the survival benefit of asignificant proportion of patients (20%) holds true in largercohorts and whether the efficacy of liposomal doxorubicincan be improved by combinations without compromisingthe low toxicity profile needs further studies.