While some anticancer agents are available for treating some types of soft tissue sarcoma (such as first-line paclitaxel for angiosarcoma or pazopanib for non-adipocytic soft tissue sarcomas), doxorubicin hydrochloride remains a centerpiece for sarcoma treatment.1-4
Yet as a monotherapy, doxorubicin offers an objective response rate (ORR) of 15% (about the same as ifosfamide) and comes at a cost of significant toxicity risks for patients.5 At doses exceeding 75 mg/m2 per cycle, doxorubicin is associated with cardiotoxicities, myelosuppression and mucositis.
Aldoxorubicin is composed of doxorubicin attached to serum albumin, leaving it biologically inactive as it circulates through the patient’s body — until it arrives in tumor tissue, where the acidic microenvironment breaks the covalent bond with albumin.
Researchers believe that this yields higher localized doses of cytotoxic drug to tumor tissues, although observers caution that aldoxorubicin accumulation in sarcomas is not empirically confirmed.
Encouraging earlier clinical safety and efficacy clinical trial data suggest that aldoxorubicin is associated with improved antitumor efficacy and reduced cardiotoxicity risk, and that it might improve patient outcomes.6
Compared with doxorubicin, aldoxorubicin was associated with few cardiotoxic effects in a randomized international phase 2b clinical trial of 126 patients, published in 2015, even at a median dose equivalent to 1500 mg/m2 doxorubicin. Only 12% of patients saw a significant decline in left ventricular ejection fraction (LVEF decline of at least 10%), for example — less than half of the 29% rate for patients administered doxorubicin.6
In this study, aldoxorubicin was also associated with more than a doubling of both overall tumor response rate (ORR; 25% vs 0%) and patient progression-free survival (PFS; 5.6 vs 2.7 months; P = .02), compared with doxorubicin.
Phase 3 trial results were reported in June 2017 at the American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago, Illinois.
The study team randomly assigned 433 patients diagnosed with sarcoma in 79 countries to receive either aldoxorubicin (350 mg/m2 intravenously every 3 weeks) or up to 3 other treatments, including dacarbazine, pazopanib, ifosfamide, or docetaxel with or without gemcitabine.7 Patients were also administered granulocyte-colony stimulating factor (G-CSF).