(P 181) REAL-WORLD EXPERIENCE WITH LIPOSOMAL DOXORUBICIN IN METASTATIC AND LOCALLY ADVANCED SARCOMA

Objective: Doxorubicin is commonly used as first-line chemotherapy in metastatic sarcoma; pegylated liposomal doxorubicin (PLD) may be considered as a potentially better tolerated alternative to free doxorubicin, with less myelosuppression, alopecia, and cardiotoxicity. In this project, we examined the efficacy and toxicity associated with using PLD as treatment for metastatic and locally advanced soft tissue and bone sarcoma.

Methods: Medical records of metastatic and locally advanced sarcoma patients treated with single agent PLD were reviewed at a single institution. Retrospective analysis was conducted to measure overall survival, progression free survival, dosage, and complications. RECIST criteria were applied retrospectively to routine imaging studies to estimate response and disease progression endpoints.

Results: 58 subjects who completed the planned treatment and had imaging appropriate for response evaluation were included in the analysis. Mean age at time of initiating therapy was 64 years (range 33-84 years). Sarcoma subtypes included liposarcoma (28%), leiomyosarcoma (21%), undifferentiated sarcoma (16%), synovial sarcoma (5%), and other subtypes (30%). 22% of patients had previously been treated with doxorubicin, in the neo-adjuvant or adjuvant setting. Patients received an average of 5 cycles of PLD. Starting dosage was 50 mg/m² every 28 days, however, reductions in the starting dose were made in 38% of cases due to anticipated tolerance, and in 21% subsequently due to side effects such as cutaneous toxicity and fatigue. Of 110 sarcoma patients initially identified as been treated with PLD, 8 were excluded from analysis because treatment was discontinued early due to infusion reaction. There were no complete responses, 12% partial response, 31% stable disease, and 57% progressive disease. Six of 18 patients with SD had PFS greater than 180 days. Mean overall survival 452 days. Mean and median PFS was 180 days and 89 days, respectively. Sixty-seven percent of participants had at least one follow-up echocardiogram, and 15% of those had some evidence of cardiotoxicity, with an ejection fraction of < 50% or 10% decrease from baseline. Of the participants with changes in ejection fraction, 67% had received prior anthracycline therapy and 33% had received a total lifetime dose of doxorubicin exceeding the recommended 500 mg/m² limit.

Conclusion: PLD is an option for treatment of advanced sarcoma, with a 12% response rate and mean progression free survival of 180 days. PLD is generally well-tolerated in an older population, but there are potential toxicities that require attention, including cutaneous toxicity and infusion reactions. A notable portion of our sample had echocardiographic changes, with decreased ejection fraction, highlighting the fact that, while PLD may be less cardiotoxic than free doxorubicin, there is potential cardiac risk.