Changes of Vascular Pattern of Tumors and Surrounding Tissue During Different Phases of Metastatic Growth

Bassermann, R

doi:10.1007/978-3-642-82635-1_32

Cited by 11 publications

(5 citation statements)

References 4 publications

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“…Obviously, drug leakage from circulating liposomes is undesirable since it increases toxicity. Regarding drug release from the RES, the clinical conditions most likely to benefit from this approach are tumours diffusely infiltrating the liver parenchyma or sinusoids, spleen, and bone marrow, such as lymphomas and, in some instances, small cell lung carcinoma (MacSween et al, 1979;Bassermann, 1986). This is also supported by preclinical work demonstrating the pharmacologic and therapeutic advantages of L-ADM in lymphoma models infiltrating liver and spleen (Mayhew et al, 1983;Gabizon et al, 1983Gabizon et al, , 1985.…”

Section: Discussionmentioning

confidence: 97%

Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin

Gabizón

Chisin²,

Amselem³

et al. 1991

Br J Cancer

131

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Summary Pharmacokinetic and imaging studies in 19 patients receiving liposome-entrapped adriamycin (L-ADM) were carried out within the framework of a Phase I clinical trial (Gabizon et al., 1989a). The formulation of L-ADM tested consisted of 0.2 gM-extruded multilamellar vesicles composed of egg phosphatidylcholine, egg-derived phosphatidyl-glycerol (PG), cholesterol, and ADM intercalated in the fluid lipid bilayer. Plasma clearance of total drug extracted from the plasma after L-ADM infusion followed a biexponential curve with a pattern similar to that reported for free ADM. The plasma concentration of drug circulating in liposome-associated form was also measured in a subgroup of seven patients. Liposomeassociated drug was found to be rapidly cleared from plasma. Its ratio to nonliposome-associated drug appeared to correlate with liver reserve, with highest ratios in patients with normal liver function. Liposome clearance, as measured by the plasma concentration of PG in three patients was slower than the clearance of liposome-associated ADM, suggesting that liposomes lose part of their drug payload during circulation. To learn about the liposome organ distribution, imaging studies were carried out with "'Indium-deferoxamine labelled liposomes of the same composition. Liposomes were cleared predominantly by liver and spleen and to a lesser extent by bone marrow in seven out of nine patients. In two patients with active hepatitis and severe liver dysfunction, there was minimal liver uptake and increased spleen and bone marrow uptake. Except for one hepatoma patient, intrahepatic and extrahepatic tumours were not imaged by liposomes, suggesting that liposome uptake is restricted to cells of the reticulo-endothelial system (RES). These observations indicate that a major fraction of this L-ADM formulation is rapidly cleared by the RES, and that the mechanism of drug delivery is probably the combined result of slow release from the RES depot and drug leakage from circulating liposomes.Liposome-entrapped adriamycin (L-ADM) has been shown to have reduced toxicity and preserved or improved antitumour efficacy in experimental animal models (reviewed in Perez-Soler, 1989;Gabizon, 1989). Recently we have carried out a Phase I clinical study (Gabizon et al., 1989a) with a formulation of L-ADM in which the drug is incorporated in the fluid bilayer of the vesicles (Amselem et al., 1990a). The results have been consistent with the preclinical observations, namely the maximal tolerated dose (MTD) of L-ADM was increased in relation to the MTD of free drug administered at the conventional 3-weekly schedule. However the dose limiting toxicity for L-ADM was, as for free ADM, myelotoxicity. Thus, although the toxicities of free ADM and L-ADM differ quantitatively, they are qualitatively similar.In this report we summarise pharmacokinetic and imaging studies with L-ADM and radiolabelled liposomes of the same composition in the Phase I study patients and a small group of additional patients with similar eligibility criteria. The...

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Section: Discussionmentioning

confidence: 97%

Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin

Gabizón

Chisin²,

Amselem³

et al. 1991

Br J Cancer

131

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“…In the present study, a tendency toward better anti-tumor effects was observed for the TAP group compared to the TA group; however, this tendency failed to reach significance. In experimental models, the blood supply to liver tumors varied with tumor size: tumors greater than 1 cm in diameter derive most of their blood supply from the hepatic artery; tumors between 0.5 and 2 mm in diameter are mainly vascularized by the portal system; and tumors of approximately 5 mm in diameter obtain their blood supply from both hepatic and portal circulation (20,21). In our study, the hepatic artery was likely the dominant tumor feeder, as the median tumor size was 15.0 mm, and hepatic arteriograms showed tumor staining in all animals.…”

Section: Discussionmentioning

confidence: 99%

Single bolus regional chemotherapy with doxorubicin versus chemoembolization in a rabbit vx2 tumor model

Cho

Shin

Soo³

et al. 2010

Diagn Interv Radiol

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“…An early report of a small randomized trial75 of systemic versus intraportal 5‐FU stimulated extensive interest because of an increase in survival for the intraportal group. The benefit however, was seen only in patients with Dukes' B tumors 76…”

Section: Chemotherapymentioning

confidence: 99%

“…Differences in the incidence of hepatic metastases were not significant. Table 8,82 summarizes the randomized adjuvant portal vein trials.…”

Section: Chemotherapymentioning

confidence: 99%

Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma

Kemeny

Fata

1999

Journal of Hepato-Biliary-Pancreatic Surgery

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Hepatic metastases from colorectal carcinoma are common and may be resected for cure. The response of liver metastases to systemic chemotherapy is low. In contrast, hepatic arterial chemotherapy produces higher response rates than systemic chemotherapy, but randomized trials have not definitely proved a survival advantage because they allowed cross over. Most adjuvant portal vein chemotherapy studies have shown a survival advantage over the control group, but it is not clear whether this benefit is from the portal vein therapy or from immediate postoperative chemotherapy, since there is rarely a reduction in liver metastases. We describe the results of systemic, hepatic artery infusion, and portal therapy for patients with liver metastases of colorectal carcinoma.

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Changes of Vascular Pattern of Tumors and Surrounding Tissue During Different Phases of Metastatic Growth

Cited by 11 publications

References 4 publications

Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin

Pharmacokinetic and imaging studies in patients receiving a formulation of liposome-associated adriamycin

Single bolus regional chemotherapy with doxorubicin versus chemoembolization in a rabbit vx2 tumor model

Arterial, portal, or systemic chemotherapy for patients with hepatic metastasis of colorectal carcinoma

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