TY - JOUR
T1 - Systemic administration of doxorubicin-containing liposomes in cancer patients
T2 - a phase I study
AU - Gabizon, A.
AU - Peretz, T.
AU - Sulkes, A.
AU - Amselem, S.
AU - Ben-Yosef, R.
AU - Ben-Baruch, N.
AU - Catane, R.
AU - Biran, S.
AU - Barenholz, Y.
N1 - Funding Information:
Accepted 11 August 1989. Supported by: Liposome Technology Inc. (Menlo Park, California), Farmitalia-Carlo Erba (Milano, Italy), and the Robert &old Fund for Applied Science Uerusalem, Israel). Correspondence and reprint requests to: Dr Albert0 Gabizon, Department of Oncology, Hadassah Medical Center, P.O.B. 12000, .Jerusalem 91120. Israel.
PY - 1989/12
Y1 - 1989/12
N2 - A clinical study was designed to evaluate the tolerance of cancer patients to liposome-associated doxorubicin (L-DXR). The liposomes used contain phosphatidylglycerol, phosphatidylcholine, cholesterol, and DXR intercalated in the lipid bilayer, and have a mean size in the range of 0.3-0.5 μm. Thirty-two patients, most of them with primary or metastatic liver cancer refractory to conventional therapy, were entered into the study. A total of 69 courses of therapy was administered by intravenous infusion of a suspension of L-DXR (0.5-2.0 mg DXR/ml) in physiologic saline at an approximate rate of 2 ml/min given on a 3-week intermittent schedule. The L-DXR and phospholipid doses were escalated from 20 mg/m2 and 0.3 g/m2 to 120 mg/m2 and 3.2 g/m2 respectively. Treatment was generally well tolerated and acute toxic effects such as nausea and vomiting were mild and infrequent. Chills and fever (>38.0°C) were observed in three patients during infusion of L-DXR and in seven patients 6-12 h after the end of infusion. Median WBC nadir counts were 2700, 2300 and 700/μl at 85, 100 and 120 mg/m2 respectively. All three patients receiving 120 mg/m2 developed grade 4 leukopenia and fever requiring intravenous antibiotics, and, in two of them, severe stomatitis (grades 3 and 4) was observed. Significant hair loss was apparent in all patients receiving doses higher than 50 mg/m2. The maximal tolerated dose of L-DXR appears to be 120 mg/m2, with leukopenia and stomatitis being the dose-limiting factors. While the subacute toxicity of L-DXR appears to be qualitatively similar to that of free DXR, its tolerance exceeds the recommended dose of free DXR (75 mg/m2) in the standard 3-weekly schedule.
AB - A clinical study was designed to evaluate the tolerance of cancer patients to liposome-associated doxorubicin (L-DXR). The liposomes used contain phosphatidylglycerol, phosphatidylcholine, cholesterol, and DXR intercalated in the lipid bilayer, and have a mean size in the range of 0.3-0.5 μm. Thirty-two patients, most of them with primary or metastatic liver cancer refractory to conventional therapy, were entered into the study. A total of 69 courses of therapy was administered by intravenous infusion of a suspension of L-DXR (0.5-2.0 mg DXR/ml) in physiologic saline at an approximate rate of 2 ml/min given on a 3-week intermittent schedule. The L-DXR and phospholipid doses were escalated from 20 mg/m2 and 0.3 g/m2 to 120 mg/m2 and 3.2 g/m2 respectively. Treatment was generally well tolerated and acute toxic effects such as nausea and vomiting were mild and infrequent. Chills and fever (>38.0°C) were observed in three patients during infusion of L-DXR and in seven patients 6-12 h after the end of infusion. Median WBC nadir counts were 2700, 2300 and 700/μl at 85, 100 and 120 mg/m2 respectively. All three patients receiving 120 mg/m2 developed grade 4 leukopenia and fever requiring intravenous antibiotics, and, in two of them, severe stomatitis (grades 3 and 4) was observed. Significant hair loss was apparent in all patients receiving doses higher than 50 mg/m2. The maximal tolerated dose of L-DXR appears to be 120 mg/m2, with leukopenia and stomatitis being the dose-limiting factors. While the subacute toxicity of L-DXR appears to be qualitatively similar to that of free DXR, its tolerance exceeds the recommended dose of free DXR (75 mg/m2) in the standard 3-weekly schedule.
UR - http://www.scopus.com/inward/record.url?scp=0024852595&partnerID=8YFLogxK
U2 - 10.1016/0277-5379(89)90350-7
DO - 10.1016/0277-5379(89)90350-7
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AN - SCOPUS:0024852595
SN - 0277-5379
VL - 25
SP - 1795
EP - 1803
JO - European Journal of Cancer and Clinical Oncology
JF - European Journal of Cancer and Clinical Oncology
IS - 12
ER -