ABSTRACT
TLC D-99 is doxorubicin encapsulated in liposomes by a pH driven remote loading process. In preclinical studies, it is essentially free of cardiac toxicity. Initial clinical evaluation of TLC D-99 on 2 schedules has been conducted at RPCI in patients with advanced cancer. Schedule A: a single dose every 3 weeks; Schedule B: daily for three days’ administration every 3 weeks. Doses of 20–90 mg/m2 were explored on Schedule A and 60 and 75 mg/m2 every 3 weeks on Schedule B. The dose limiting toxicity was myelosuppression, principally leucopenia. Non-hematologic toxicities were less than expected from an equivalent dose of free doxorubicin. Fever, chills and malaise, rarely seen with free doxorubicin, were frequent. Non-hematologic toxities were generally less on Schedule B than Schedule A. The recommended dose for phase II studies is 75 mg/m2 on either schedule. The study demonstrates the safety and reduced non-hematologic toxicities of a commercially produced liposomal doxorubicin.
