Phase i/ii study of fluosol®-DA and 100% oxygen as an adjuvant to radiation in the treatment of advanced squamous cell tumors of the head and neck

Lustig, Robert A.; McIntosh-Lowe, Norma; Rose, Christopher M.; Haas, J.; Krasnow, Steven H.; Spaulding, Monica B.; Prosnitz, Leonard R.

doi:10.1016/0360-3016(89)90967-x

Cited by 72 publications

(10 citation statements)

References 13 publications

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“…A very similar side effect profile was also observed when the now well-accepted injectable lipid emulsions for parent-era1 nutrition were first introduced [128]. Essentially the same untoward reactions were also reported for Fluosol in the phase 1/11 clinical studies designed to investigate its use as radiosensitizer in cancer therapy [129,130].…”

Section: Highly Concentrated Fluorocarbon Emulsionssupporting

confidence: 55%

Fluorocarbon‐Based in vivo Oxygen Transport and Delivery Systems

Riess

1991

Vox Sanguinis

132

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The approval of Fluosol, a fluorocarbon emulsion for oxygenating the myocardium during the transluminal coronary angioplasty procedure, is a landmark in the field of injectable oxygen carriers, the so-called blood substitutes. This review discusses the advances made since this first emulsion was initially developed about 12 years ago. Attention is focused on the progress achieved in the preparation and selection of new, better-defined and faster-excreted fluorocarbons, and better surfactants, improved emulsions, knowledge of structure/property relationships along with an improved understanding of the physiologic response to their administration. These advances have led to the development of a second generation of highly concentrated, fluid and stable injectable oxygen carriers suitable for a broad range of clinical applications. Prospects for further progress and future generations of emulsions are also outlined.

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Section: Highly Concentrated Fluorocarbon Emulsionssupporting

confidence: 55%

Fluorocarbon‐Based in vivo Oxygen Transport and Delivery Systems

Riess

1991

Vox Sanguinis

132

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“…Similarly, Figure 2b shows the relative change in median P02 after 5 min of exposure to HBO, HBC and bretylium/HBC. Henk, 1986;Lustig et al, 1989Lustig et al, , 1990Dische, 1991;Rockwell et al, 1991 (Rojas, 1991). Martin et al (1993) analysed the effect of crbogen breathing on tumour oxygenation with the pO2 histograph in head and neck cancer patients with metastases to cervical lymph nodes.…”

Section: Treatment With Hyperbaric Carbogenmentioning

confidence: 99%

The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation

Brizel

Lin²,

Johnson³

et al. 1995

Br J Cancer

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S_mman Hyperbaric oxygen (HBO) has been proposed to reduce tumour hypoxia by increasing the amount of dissolved oxygen in the plasma. That this actually occurs has not been verified experimentally. This study was performed to explore changes in tumour oxygenation induced by treatment with normobaric and hyperbanrc oxygen and carbogen. R323OAc mammary adenocarcinomas were implanted into Fischer 344 rats. Arterial blood gases. blood pressure and heart rate were monitored. Tumour oxygenation was measured polarographically in five sets of animals. They received either normobaric 100% oxygen, hyperbaric (3 atmospheres, atm) 100% oxygen. normobaric carbogen or hyperbanrc (3 atm) carbogen (HBC) ± bretylium.HBO reduced the mean level of low pO, values (< 5 mmHg) from 0.49 to 0.07 (P = 0.0003) and increased the average median pO2 from 8 mmHg to 55 mmHg (P = 0.001). HBC reduced the level of low pO values from 0.82 to 0.51 (P = 0.002) and increased median pO from 2 mmHg to 6 mmHg (P = 0.05). Normobaric oxygen and carbogen did not change tumour oxygenation significantly. Sympathetic blockade with bretylium before HBC exposure improved oxygenation significantly more than HBC alone (low pO2 0.55-0.17, median pO2 4-17 mmHg). HBO and hyperbaric carbogen improved tumour oxygenation in this model, while normobaric oxygen or carbogen had no effect. Syvmpathetic-mediated vasoconstriction dunrng hyperbaric carbogen caused it to be less effective than HBO. This mechanism also appeared to operate during normobanrc carbogen breathing. (Brady et al.. 1981;Henk, 1986;Dische. 1991). During this penrod, several investigators measured tumour oxygenation with simple polarographic microelectrode systems. They showed that HBO improved tumour oxygenation in animals and humans (Jamieson and van den Brenk, 1963Brenk, , 1965.The effects of carbogen (95% oxygen 5% carbon dioxide) breathing were also studied. There were two reasons for using carbogen: the carbon dioxide component would help to maintain tumour blood flow by counteracting oxygeninduced vasoconstriction and also increase oxygen delivery by shifting the haemoglobin-oxygen dissociation curve to the right (Rojas. 1991). Some studies showed that carbogen breathing improved tumour oxygenation and blood flow while others did not (Kruuv et al.. 1967;Inch et al., 1970). These studies were primarily descriptive in nature and did not explore potential mechanisms that might explain the experimental data.A major limitation of the early polarographic measurement studies was the inability to sample more than a few points in any given tumour. The development of a computercontrolled polarographic device (pO2 histograph. Eppendorf. Hamburg, Germany) has led to a resurgence in the measurement of tumour oxygenation. Rapid in situ measurement of multiple points within a tumour is now possible.

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“…By improving tissue oxygenation, Fluosol-DA may also prove an adjuvant to radiotherapy. Clinical trials are in progress [27].…”

Section: Fluosol-damentioning

confidence: 99%

Red blood cell substitutes: current status

Jones¹

1995

British Journal of Anaesthesia

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There are two main indications for the transfusion of red cells: severe haemorrhage and chronic symptomatic anaemia for which no specific therapy exists. In both circumstances, the aim of red cell transfusion is to improve the oxygen supply to the tissues by raising the oxygen content of the blood, according to the equations: oxygen delivery = cardiac output x arterial oxygen content arterial oxygen content = haemoglobin concentration x % saturation x 1.34 [34] The transfusion of allogeneic blood (or plasma or red cells) involves many hoards (see table 1), some of which may be reduced or avoided. For example, the patient's own blood rather than allogeneic blood may be transfused: by 1990 more than 5% of units collected in the USA were of autologous blood [42]. In the United Kingdom, the National Transfusion Service is now, in some regions at least, prepared to organize preoperative donation of the patient's blood. Other forms of autologous transfusion, intraoperative haemodilution and red cell salvage, are already practised in the UK. Finally, a growing awareness of the compensatory mechanisms which, in anaemia, preserve oxygen delivery despite a lowered oxygen-carrying capacity, has prompted surgeons and anaesthetists to accept haemoglobin concentrations as low as 7 g dl~' in some patients. Compensatory mechanisms in anaemia Experiments in animals and healthy volunteers have shown that, in acute normovolaemic anaemia induced by withdrawing blood and replacing it with dextran 70, oxygen delivery is at its peak, not at the normal haemoglobin concentration of about 13gdl-', but at 10 g dl" 1 (see fig. 1). Two mechanisms, both induced by the lowered haemoglobin concentration, are believed to be responsible : an increase in cardiac output and a reduction in blood viscosity, which enhances peripheral flow [28]. More recently, attention has focused on the fact that, in acute normovolaemic anaemia at a haemoglobin concentration of 7 g dl" 1 , the same

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Phase i/ii study of fluosol®-DA and 100% oxygen as an adjuvant to radiation in the treatment of advanced squamous cell tumors of the head and neck

Cited by 72 publications

References 13 publications

Fluorocarbon‐Based in vivo Oxygen Transport and Delivery Systems

Fluorocarbon‐Based in vivo Oxygen Transport and Delivery Systems

The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation

Red blood cell substitutes: current status

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