Valrubicin is a semisynthetic analog of the anthracycline doxorubicin, and is administered by infusion directly into the bladder. Valrubicin is an anthracycline that affects a variety of inter-related biological functions, most of which involve nucleic acid metabolism. It readily penetrates into cells, where after DNA intercalation, it inhibits the incorporation of nucleosides into nucleic acids, causes extensive chromosomal damage, and arrests cell cycle in G2. Although valrubicin does not bind strongly to DNA, a principal mechanism of its action, mediated by valrubicin metabolites, is interference with the normal DNA breaking-resealing action of DNA topoisomerase II. Valrubicin is FDA approved drug, sold under the trade name Valstar.

Aldoxorubicin (INNO-206) is a tumor-targeted doxorubicin conjugate developed by CytRx for treating relapsed and refractory sarcomas, especially L-sarcomas. Aldoxorubicin is a rationally-engineered cytotoxic which delivers a well-established anti-cancer agent, doxorubicin, into the tumor. Currently, in late-stage clinical trials, Aldoxorubicin appears to overcome the key limitations of doxorubicin, including cumulative dose restrictions. Aldoxorubicin utilizes an acid-sensitive linker that selectively binds to albumin, which may allow the cytotoxic payload to preferentially accumulate in the tumor and potentially spare the surrounding healthy tissue. This mechanism leverages the tumor's low pH environment and accompanying dependency upon circulating albumin to fuel growth, to enable the delivery of multifold times the standard dosing of doxorubicin. The preferential uptake of Aldoxorubicin by tumor tissue and the acid sensitive release of doxorubicin allow for Aldoxorubicin to be a very promising anticancer agent. In phase I and II trials, Aldoxorubicin demonstrates superior efficacy over doxorubicin. Although the studies were not powered for OS, Aldoxorubicin shows improved PFS and tumor response in comparison to doxorubicin. The safety profile was also comparable to that of doxorubicin. Similarly, results from the recent phase III study showed a benefit in PFS in the leiomyosarcoma subtypes.