High intratumoural accumulation of stealth® liposomal doxorubicin (Caelyx®) in glioblastomas and in metastatic brain tumours
AuthorKoukourakis, M. I.; Koukouraki, S.; Fezoulidis, I.; Kelekis, N.; Kyrias, G.; Archimandritis, S.; Karkavitsas, N.
The blood-brain barrier is a major obstacle for the chemotherapeutic drugs to effectively reach primary or secondary brain tumours, Stealth® liposomal drugs are highly accumulated in tumoural tissues. In the present study we investigated the relative accumulation of 99mTc-DTPA radiolabelled stealth® liposomal doxorubicin (Caelyx®) in 10 patients with metastatic brain tumours and five patients with brain glioblastoma undergoing radiotherapy. Patients with metastatic brain lesions were treated with 10 consecutive fractions of radiotherapy (whole brain, 3 Gy/fraction, day 1-12) followed by a booster dose of 9 Gy (3 Gy/fraction, day 21-23), Caelyx®, at a dose of 25 mg mg -2 was given on day 1 and on day 21. Radiolabelled Caelyx® accumulation was 13-19 times higher in the glioblastomas and 7-13 times higher in the metastatic lesions, as compared to the normal brain. The drug accumulation in the tumoural areas was 40-60% of the accumulation in the bone marrow of the skull bones. The normal brain radioactivity was <4% of the bone marrow, confirming an important shielding effect of the blood-brain barrier in the normal but not in the tumoural tissue. Four of 10 patients with metastatic 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® liposomal drugs selectively overcome the blood-brain barrier in the tumoural areas. The clinical importance of this observation is now under investigation. (C) 2000 Cancer Research Campaign.
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