High intratumoural accumulation of stealth (R) liposomal doxorubicin (Caelyx (R)) in glioblastomas and in metastatic brain tumours

The blood-brain barrier is a major obstacle for the chemotherapeutic drugs to effectively reach primary or secondary brain tumours. Stealth(R) liposom al drugs are highly accumulated in tumoural tissues. In the present study w e investigated the relative accumulation of Tc-99m-DTPA radiolabelled steal th(R) liposomal doxorubicin (Caelyx(R)) in 10 patients with metastatic brai n tumours and five patients with brain glioblastoma undergoing radiotherapy . Patients with metastatic brain lesions were treated with 10 consecutive f ractions of radiotherapy (whole brain, 3 Gy/fraction, day 1 -12) followed b y a booster dose of 9 Gy (3 Gy/fraction; day 21-23). Caelyx(R), at a dose o f 25 mg mg(-2) was given on day 1 and on day 21. Radiolabelled Caelyx(R) ac cumulation was 13-19 times higher in the glioblastomas and 7-13 times highe r in the metastatic lesions, as compared to the normal brain. The drug accu mulation in the tumoural areas was 40-60% of the accumulation in the bone m arrow of the skull bones. The normal brain radioactivity was <4% of the bon e marrow, confirming an important shielding effect of the blood-brain barri er in the normal but not in the tumoural tissue. Four of 10 patients with m etastatic lesions showed a complete response in CT-scan performed 2 months following therapy. There was no severe toxicity related to radiotherapy or to chemotherapy noted. It is concluded that stealth(R) liposomal drugs sele ctively overcome the blood-brain barrier in the tumoural areas. The clinica l importance of this observation is now under investigation. (C) 2000 Cance r Research Campaign.