US-based biopharmaceutical firm CytRx has released positive top-line efficacy results from a Phase IIb clinical trial, which evaluated the efficacy and safety of aldoxorubicin compared with doxorubicin in patients with first-line metastatic, locally advanced or unresectable soft tissue sarcomas (STS).
The multicentre, randomised, open-label global trial was carried out at 31 centres and a total of 123 patients were examined, who were administered with either aldoxorubicin or doxorubicin in a 2:1 randomisation respectively.
In the trial, 83 patients with advanced soft tissue sarcomas were given a dosage of aldoxorubicin 350mg/m2 as a 30-minute intravenous infusion on day 1 of each cycle, while doxorubicin (75 mg/m2) was administered to 40 subjects as a five to 30 minute infusion on day one of each cycle.
A cycle of therapy was defined as a three-week (21-day) period and multiple cycles were administered until the patient was withdrawn from therapy or until a maximum of six cycles were administered.
In these patients, CT scans were obtained every six weeks to evaluate tumour response and progression, and adverse events were collected in a case report form.
The primary endpoint of the trial was progression-free survival (PFS) as determined by both investigators at study sites and by a blinded radiology review carried out at an independent central laboratory, while secondary endpoints were overall response rates and PFS at six months for each group, and overall survival will be reported when the clinical trial is complete.
The company said that aldoxorubicin combines the chemotherapeutic agent doxorubicin with a new linker-molecule that binds to albumin in the blood to allow for delivery of higher amounts of doxorubicin (three-and-a-half to four times) without the major dose-limiting toxicities seen with administration of doxorubicin alone.
In the trial aldoxorubicin showed 80%-100% improvement over doxorubicin in PFS as first-line therapy in advanced soft tissue sarcomas.
Sarcoma Oncology Center study principal investigator Sant Chawla said aldoxorubicin is the first and only single agent to surpass doxorubicin as a first-line treatment for soft tissue sarcomas.
"Previous results from this trial presented at the Connective Tissue Oncology Meeting in October indicated that subjects treated with aldoxorubicin demonstrated no significant cardiotoxicity, whereas doxorubicin shows cardiotoxicity at certain cumulative dose levels," Chawla said.
"No subjects left the study due to aldoxorubicin side effects. These findings together suggest that aldoxorubicin could become the treatment of choice for soft tissue sarcomas.
"Yet this drug's potential extends much further because doxorubicin in particular and anthracyclines in general are indicated as first- or second-line therapy for many other common cancers including breast, ovarian, small-cell lung, multiple myeloma, acute myelocytic leukemia and more."
In the trial aldoxorubicin was observed to be safe and well tolerated, while all adverse events in subjects treated with the drug were consistent with the known side effects of doxorubicin, and were resolved before the administration of the next dose and did not require treatment discontinuation.
Image: Labelled CT image of undifferentiated soft tissue sarcoma in left lung of young child, showing involvement of pericardium and chest wall, and mediastinal shift. Photo: courtesy of Wikimedia Commons.