A phase II study of a new formulation of nonpegylated liposomal doxorubicin (doxorubicin GP-pharm) as first-line treatment in patients with advanced soft-tissue sarcomas (STS) who are age 65 or older: A GEIS trial.

Abstract

10072 Background: Doxorubicin remains the standard of care for STS. Its use has been limited due to bone marrow and cardiac toxicity, specially in elderly patients (pts). Doxorubicin GP-Pharm (Sarcodoxome)(DX-GP) is a non-pegylated liposomal formulation containing lipochromane-6. Previous Phase I study suggested activity and a low cardiac toxicity (CTOS 2008) Methods: Multicenter multinational Phase II prospective trial in advanced or metastatic STS pts aged ≥64 yr, to asses efficacy and safety of DX-GP in first line setting. Eligibility: ECOG ≤ 2, measurable disease by RECIST and acceptable hematologic, liver, renal and cardiac function. DX-GP 80 mg/m2 was administered IV over 60 minutes on day 1 every 3 weeks for a maximum of 6 cycles. Troponin, BNP, ECG and MUGA were performed every 2 cycles to evaluate cardiac function. An amendment (2009) expanded inclusion criteria to pts over than 45 years (thus only 4 pts <65 years old have been recruited). Results: From February 2007 to January 2010, 37 pts (13 male and 24 female) were included (12 retroperitoneum/trunk, 8 extremities, 4 uterine, 4 visceral). Median age 74 years (51-87). Non-resectable locally advanced 9, metastatic 28 pts. Nr of cycles: 116, mean 3(1-6). Grade 3/4 toxicities: Neutropenia 23 (62%), Leukopenia 10 (27%), febrile neutropenia 6 (16%), thrombopenia 4 (10%), anemia 2(5%) pts. Non-hematological toxicities were grade 3 asthenia 4 (10%) pts and grade II stomatitis and alopecia among others. 2 pts presented cardiac toxicity grade 1 and grade 5 respectively. Non cumulative cardiac toxicity. One treatment-related death. Efficacy (PR or SD) was seen in 8/26 (30%) evaluable pts. Median PFS was 3 (CI95% 1.9-7.4) months. Median survival time 14.4 (CI95% 6.3-27.1) months. Conclusions: DX-GP is a new liposomal DX that shows acceptable toxicity profile and efficacy at 80 mg/m2 in elderly pts with STS. Studies are needed in younger pts.