High intratumoral accumulation of stealth liposomal doxorubicin in sarcomas - Rationale for combination with radiotherapy

Sarcomas are radioresistant tumors, the only curative therapy being radical surgical resection. Stealth(R) liposomal doxorubicin (Caelyx(R)) is a nove l drug formulation that allows prolonged circulation and high intratumoral concentration. This study investigates the concurrent use of radiotherapy w ith Caelyx(R) in a cohort of 7 patients with locally advanced or recurrent sarcoma. Radiotherapy was given as a standard fractionation regimen to a to tal dose of 70 Gy. Caelyx(R) was given as a 30-min infusion at a dose of 25 mg/m(2) every 2 weeks. Scintigraphic imaging with Caelyx-99mTc-DTPA showed an increased (2.8 +/- 0.9 times higher) intratumoral drug accumulation com pared to the surrounding healthy tissue. The regimen was well tolerated wit hout any severe hematological or systemic toxicity. 'In field' radiation to xicity was not increased. Complete response was observed in 4/7 cases. It i s concluded that combined chemo-radiotherapy with stealth(R) liposomal doxo rubicin for locally advanced sarcomas is feasible and promising, the benefi t expected from the unique ability of the stealth(R) liposomes to accumulat e selectively in the tumoral tissue.