Aldoxorubicin (A) has demonstrated superior anti-tumor efficacy and lack of cumulative cardiac toxicity in multiple studies. A is doxorubicin (D) with a linker which rapidly binds in vivo to albumin after iv administration. We studied the combination of A administered on Day 1 with continuous infusion (CI) of ifosfamide/Mesna (I-M) days 1-14, in patients with sarcomas to evaluate efficacy and toxicity.
27 patients entered the study at one of 2 dose levels of A:170 or 250 mg/m2 (125 or 185 mg/m2 D equiv) administered on Day 1. I-M (1 g/m2 of each per day) was given up to 14 days as a CI via an out-patient portable pump. Chemotherapy cycles were repeated at 28 day interval. I-M was limited to a maximum of 6 cycles to avoid cumulative marrow toxicity, but A was continued in responding patients for clinical benefit. Subjects were followed for tumor response by CT scans and echocardiogram for cardiac toxicity every 8 weeks along with standard labs.
Of the 27 patients enrolled as of May 1, 2016, the results of 24 evaluable patients are presented here. Twenty of the 24 patients had soft tissue sarcoma, 2 had metastatic osteosarcoma and 2 had dedifferentiated chondrosarcoma. Eight of 24 patients (33%) had a partial response (PR), 15/24 (62%) had stable disease (SD) and only 1/24 (5%) had progressive disease with over all disease control rate of 95% (PR + SD). Eleven of 24 (46%) patients had received at least 6 cycles of A (cumulative D equivalent more than 1000 mg/m2). Four patients were considered surgically resectable after 6 cycles of chemotherapy with percent of tumor necrosis of 95% and 90% in one patient each and 80% in two patients. Median duration of PFS was 6+ (2-19+) months. The most prevalent toxicity was gr 3 or 4 neutropenia. Four patients had SAEs of febrile neutropenia. There was no clinical cardiac toxicity/ congestive heart failure. No patient had LVEF
The combination of A + I-M appears to be superior in anti-tumor efficacy to D/I-M with durable responses. A + I-M combination is quite tolerable with expected reversible hematologic toxicity. Of the 46% patients who received more than 1000 mg /m2 of D equivalent; no cardiac toxicity was observed.
Clinical trial identification
Legal entity responsible for the study
S.P. Chawla: Research support from CytRx Corporation. S. Chawla, K. Sung, S. Wieland, D. Levitt: Employee of CytRx Corporation. All other authors have declared no conflicts of interest.