Single-agent aldoxorubicin therapy showed a significantly higher progression-free survival (PFS) and tumor response rate compared with doxorubicin in patients with advanced soft-tissue sarcoma, according to a study published online ahead of print in JAMA Oncology.1 

Standard therapy for advanced soft-tissue sarcoma has remained mostly the same for decades. Aldoxorubicin, a prodrug of doxorubicin, has shown clinical activity against soft-tissue sarcoma in phase 1 studies.

Researchers in this international, multicenter, phase 2b randomized study sought to determine the efficacy and safety of aldoxorubicin vs doxorubicin in patients with advanced soft-tissue sarcoma.

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A total of 123 patients were randomly assigned 2:1 to receive aldoxorubicin 350 mg/m2 (dose equivalent to doxorubicin 260 mg/m2; n=83) or doxorubicin (75 mg/m2; n=40) administered once every 3 weeks for up to 6 cycles. Median patient age was 54.0 (21 to 77 years); 34% had leiomyosarcoma.

Results showed a significantly improved median PFS in the aldoxorubicin group (5.6 months [95% CI: 3.0 to 8.1]) vs the doxorubicin group (2.7 months [95% CI: 1.6 to 4.3]; P=0.02).

The rate of 6-month progression-free survival was also significantly higher in patients who received aldoxorubicin (46% and 23%, respectively; P=0.02). Median overall survival was 15.8 months (95% CI, 13.0 to not available) with aldoxorubicin and 14.3 months (95% CI, 8.6-20.6) with doxorubicin (P=0.21).

Overall tumor response rate (by Response Evaluation Criteria in Solid Tumors, version 1.1) by independent review was higher with aldoxorubicin than with doxorubicin (25% [20 patients, all partial response] vs 0%).

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In regard to safety, grade 3 or 4 neutropenia was more frequent with aldoxorubicin than with doxorubicin (24 [29%] vs 5 [12%]), but not grade 3 or 4 febrile neutropenia (12 [14%] vs 7 [18%]).

No acute cardiotoxic effects were observed with either treatment, although left ventricular ejection fraction less than 50% occurred in 3 of 40 patients receiving doxorubicin.

The researchers concluded that further investigation of aldoxorubicin is warranted in this patient population.


  1. Chawla SP, Papai Z,  Mukhametshina G, et al. First-line aldoxorubicin vs doxorubicin in metastatic or locally advanced unresectable soft-tissue sarcoma a phase 2b randomized clinical trial. [published online ahead of print September 17, 2015]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.3101