Doxorubicin is a workhorse chemotherapy widely used across solid tumors and remains
the first-line standard for advanced soft-tissue sarcoma, but its use
is limited by irreversible, cumulative cardiotoxicity that can lead to heart failure.
Aldoxorubicin is designed to deliver tumor-targeted doxorubicin with improved cardiac
safety compared with conventional doxorubicin.
Aldoxorubicin is a covalent albumin-binding pro-drug of doxorubicin designed
to keep free doxorubicin levels low in systemic circulation while enabling
targeted release inside tumors.
Aldoxorubicin (aldox) covalently binds circulating albumin; albumin-bound
aldoxorubicin accumulates in tumors and is taken up by tumor cells, where
its acid-sensitive linker cleaves in the acidic tumor microenvironment and
in intracellular endosomal/lysosomal compartments to release doxorubicin (dox)
locally.
Gong J et al., Drug Des Devel Ther 2018
— Narrative review: across phase II/III trials aldoxorubicin extends PFS vs doxorubicin in first-line STS and maintains a markedly lower cardiotoxicity signal.
Eilber F et al., ASCO 2017 (Abstract 11051)
— Phase Ib: aldoxorubicin 250 mg/m² + continuous-infusion ifosfamide/mesna in 27 STS pts produced a 42 % partial-response rate, median PFS not yet reached and zero LVEF declines >20 % despite >700 mg/m² doxorubicin-equivalent exposure.
Reddy SB et al., ASCO 2017 (Abstract 11000)
— Phase III interim report: aldoxorubicin improved PFS in North-American and L-sarcoma subsets and cut LVEF < 50 % events to 2.8 % vs 12.8 % with doxorubicin.
Chawla SP et al., ASCO 2015 (Abstract 10546)
— Pooled safety (n = 142): cumulative doses up to 5.4 g/m² (≈12 × doxorubicin limit) showed 0 cases of clinical CHF and no patient’s LVEF fell below the institutional normal threshold.
Chawla SP et al., JAMA Oncol 2015
— Randomised phase IIb (n = 126) in relapsed STS: aldoxorubicin doubled median PFS (5.6 vs 2.7 mo) and tripled objective response (25 % vs 9 %) with no acute cardiotoxicity.
Chawla SP et al., Cancer 2015
— Phase 1b/2 (n = 25) set MTD at 350 mg/m²; in STS, ORR 38 % and median PFS 11.3 mo were achieved with negligible cardiac events.
Mita MM et al., Cancer Chemother Pharmacol 2015
— Full PK: albumin-bound t½ ≈ 21 h, Vd ≈ 4 L/m², clearance ≈ 0.14 L h⁻¹ m⁻²; free doxorubicin/doxorubicinol levels <1 % of total, rationalising the low cardiotoxic risk.
Mita AC et al., ASCO 2015 (Abstract e21526)
— Pilot in AIDS-related Kaposi’s sarcoma (n = 9): objective responses in two-thirds of pts and marked HHV-8 reduction; heart function preserved.
Levitt DJ et al., ASCO 2013 (Abstract 2550)
— Phase 1b combo aldoxorubicin 320 mg/m² + doxorubicin 35 mg/m²: tolerated up to 90 % of single-agent aldoxorubicin MTD; 1 PR and 6 SD (n = 10); no cardiac signal.
