A phase 1B/2 study of aldoxorubicin in patients with soft tissue sarcoma

BACKGROUND Aldoxorubicin, a prodrug of doxorubicin, covalently binds to serum albumin, allowing for the administration of much higher doses of doxorubicin in a previous clinical study. The current phase 1B/2 study evaluated the safety of aldoxorubicin, including preliminary efficacy and safety of its maximum tolerated dose (MTD). METHODS Patients aged 18 to 70 years with recurrent/refractory malignant solid tumors received aldoxorubicin at a dose of 230 mg/m2, 350 mg/m2, or 450 mg/m2 (170 mg/m2, 260 mg/m2, or 335 mg/m2 doxorubicin equivalents, respectively) by intravenous infusion once every 21 days for up to 8 consecutive cycles. RESULTS A total of 25 patients were enrolled, including 17 patients (68%) with advanced soft tissue sarcoma (STS). The MTD of aldoxorubicin was 350 mg/m2; dose-limiting toxicities included grade 4 neutropenia and grade 3 febrile neutropenia (NCI CTCAE v4.0). Drug-related adverse events included myelosuppression, nausea, fatigue, alopecia, stomatitis, vomiting, and oropharyngeal pain. No clinically significant cardiac toxicities were reported. Seven patients (28%) had elevated serum troponin levels while taking part in the study, but these elevations were not clinically significant or associated with cardiac findings. A partial response was achieved in 20% of patients, and stable disease was reported in 40% of patients. The median progression-free survival was 4.80 months, and the median overall survival was 11.25 months. Among patients with STS who were treated at the MTD (13 patients), a partial response was achieved in 38% and stable disease in 46%; the median progression-free survival was 11.25 months and the median overall survival was 21.71 months. CONCLUSIONS Aldoxorubicin at a dose of 350 mg/m2 administered once every 21 days for up to 8 cycles was found to be acceptably safe and demonstrated preliminary efficacy in patients with advanced solid tumors, including STS. Further investigation of aldoxorubicin is ongoing. Cancer 2015;121:570–579. © 2014 American Cancer Society.