Phase I trial of dose-intense liposome-encapsulated doxorubicin in patients with advanced sarcoma

To define the maximum-tolerated dose (MTD) of liposome-encapsulated doxorubicin (LED) when used every 2 weeks with granulocyte colony-stimulating factor (G-CSF) in patients with advanced soft tissue sarcoma.

Doxorubicin encapsulated in egg phosphatidylcholine/cholesterol liposomes was given to patients with sarcoma in a disease-specific phase I trial. The initial dose was 75 mg/m2 with G-CSF 5 micrograms/kg. The MTD was defined as the highest dose that could be given every 2 weeks.

Twenty-nine patients participated in this study. Major toxicities included myelosuppression, nausea and vomiting, fatigue, and mucositis. Eight patients were hospitalized for nadir fever. No cardiotoxicity was seen. The MTD was LED 105 mg/m2 with G-CSF 5 micrograms/kg. LED 120 mg/m2 resulted in tolerable, albeit prominent, acute toxicity, but did not permit recycling of therapy on day 15. Among 26 patients with soft tissue sarcoma, 23 had measurable disease, of whom three achieved a partial response (13%; 95% confidence interval, 2% to 34%).

LED can be administered every 2 weeks at a dose of 105 mg/m2 with G-CSF support, which provides a dose-intensity of 52.5 mg/m2/wk. To exceed this intensity, the dose of LED that would have to be administered every 3 weeks would be greater than 157.5 mg/m2. A formal phase II trial is needed to estimate better the true response rate.