期刊
BRITISH JOURNAL OF CANCER
卷 83, 期 10, 页码 1281-1286出版社
CHURCHILL LIVINGSTONE
DOI: 10.1054/bjoc.2000.1459
关键词
brain metastasis; glioblastoma; stealth liposomal doxorubicin; radiotherapy
类别
The blood-brain barrier is a major obstacle for the chemotherapeutic drugs to effectively reach primary or secondary brain tumours. Stealth(R) liposomal drugs are highly accumulated in tumoural tissues. In the present study we investigated the relative accumulation of Tc-99m-DTPA radiolabelled stealth(R) liposomal doxorubicin (Caelyx(R)) 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(R), at a dose of 25 mg mg(-2) was given on day 1 and on day 21. Radiolabelled Caelyx(R) 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(R) 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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