Fluosol® and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: Results of a phase I/II study

Lustig, Robert A.; Lowe, Norma; Prosnitz, Leonard R.; Spaulding, Monica B.; Cohen, Martin H.; Stitt, Judith A.; Brannon, Richard B.

doi:10.1016/0360-3016(90)90140-f

Cited by 29 publications

(6 citation statements)

References 15 publications

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“…These cells are resistant to radiation therapy and to certain anticancer drugs because O 2 participates in the reactions that produce DNA damage. Numerous experimental studies have established that PFC emulsions could deliver O 2 deep into tumor regions that would otherwise be hypoxic, thereby improving the response of tumor cells to radio and chemotherapy. ,,− Phase I/II clinical evaluation of Fluosol as an adjuvant to radiation in non-small-cell carcinoma in the lung demonstrated that large doses of PFC (∼10 g/kg in 5−7 weeks) could be administered without significant toxicity . Although these early clinical trials were considered encouraging, ,− further studies were not initiated.…”

Section: Further Potential Indications and Uses Of Fluorocarbon Emuls...mentioning

confidence: 99%

“…Numerous experimental studies have established that PFC emulsions could deliver O 2 deep into tumor regions that would otherwise be hypoxic, thereby improving the response of tumor cells to radio and chemotherapy. ,,− Phase I/II clinical evaluation of Fluosol as an adjuvant to radiation in non-small-cell carcinoma in the lung demonstrated that large doses of PFC (∼10 g/kg in 5−7 weeks) could be administered without significant toxicity . Although these early clinical trials were considered encouraging, ,− further studies were not initiated. Combination of a concentrated PFOB emulsion with hyperbaric (3 atm) O 2 selectively increased the radiation sensibility of tumors relative to normal tissues .…”

Section: Further Potential Indications and Uses Of Fluorocarbon Emuls...mentioning

confidence: 99%

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Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

2001

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Pharmaceutical Corporation in San Diego; however, the opinion expressed here are solely his and not necessarily those of the Corporation. Jean G. Riess received his chemical engineer and doctorat-e `s-sciences degrees (the latter with Professor Guy Ourisson in 1963) from the University of Strasbourg. He then spent two years with John Van Wazer at Monsanto in Saint-Louis, MO, learning some phosphorus and transitionmetal chemistry. In 1968 he became Professor at the University of Nice, France, where he founded, directed, and eventually became honorary director of the Unite ´de Chimie Mole ´culaire (associated with the Centre National de la Recherche Scientifique). His research successively involved phosphorus chemistry, transition-metal chemistry, organometallics, and eventually perfluorochemicals. His present interests are in fluorocarbons, fluorinated amphiphiles, and their colloid chemistry, including fluorocarbon emulsions for in vivo O 2 delivery, fluorinated self-assemblies, and drug delivery systems. Professor Riess has published about 360 papers and holds ca. 25 patents. He has served on numerous councils and committees and has chaired or co-chaired international conferences on phosphorus chemistry and blood substitutes. He has won awards from the French Academy of Sciences, French Chemical Society, Alexander von Humboldt Stifftung, City of Nice and Controlled Release Society, as well as Alliance's first Distinguished Contribution Award. He holds an honorary Research Associate position at the University of California at San Diego and sits on the Board of Directors of Alliance Pharmaceutical Corp.

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Section: Further Potential Indications and Uses Of Fluorocarbon Emuls...mentioning

confidence: 99%

Section: Further Potential Indications and Uses Of Fluorocarbon Emuls...mentioning

confidence: 99%

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

2001

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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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“…Teicher 25 ), and Fluosol-DA was tested for oxygenating tumors in combination with radiotherapy for carcinoma of the lung (e.g. Lustig et al 26 ). The perflubron-based oxygen carrier Oxygent TM (Alliance Pharmaceutical Corp., San Diego, USA) has been used as a blood substitute in over 1400 surgical patients in studies similar to those described by Spahn et al 27 , demonstrating a reduction in donor blood in a 492 patient Phase III trial 28 .…”

Section: Background: Pfc Liquid Ventilation and Blood Substitutesmentioning

confidence: 99%

Feasibility of lung cancer hyperthermia using breathable perfluorochemical (PFC) liquids. Part I: Convective hyperthermia

Sekins¹,

Leeper

Hoffman

et al. 2004

International Journal of Hyperthermia

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Clinical studies have shown that hyperthermia in combination with radiotherapy and/or chemotherapy may be effective in the treatment of advanced cancer. No method of lung hyperthermia, however, has been accepted as standard or superior. This investigation sought to demonstrate in animals the thermal and physiologic feasibility of lung hyperthermia induced using heated breathable perfluorochemical (PFC) liquids, a method termed liquid-filled lung convective hyperthermia (LCHT). The ability to use LCHT is rooted in the development of both PFC liquid ventilation, now in clinical development with the PFC perflubron (LiquiVent), and a PFC blood substitute also in late Phase III trials (Oxygent). As LCHT background, the PFC technologies and biology are first reviewed. The physical properties of a variety of PFCs were evaluated for LCHT and it was concluded that more than one liquid is suitable based on such properties. Using total liquid ventilation type devices, LCHT was shown to deliver successfully localized (lobar) lung heating in sheep, and bilateral whole lung heating and whole-body hyperthermia in rabbits, cats and lambs. During LCHT, lung parenchymal temperatures were uniform (<1 degree C) across heated regions. In addition, based on patterns relating lung tissue temperatures to inspiratory and expiratory PFC liquid temperatures in the endotracheal tube, LCHT may minimize invasive thermometry requirements in the lung. Based on acute experiments, it was concluded that LCHT appears feasible and may simplify lung hyperthermia. It was recommended that potentially synergistic combinations of LCHT with other whole-body hyperthermia or local heating modalities, and with chemotherapeutic lung drug delivery, also be explored in the future.

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Fluosol® and oxygen breathing as an adjuvant to radiation therapy in the treatment of locally advanced non-small cell carcinoma of the lung: Results of a phase I/II study

Cited by 29 publications

References 15 publications

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

Oxygen Carriers (“Blood Substitutes”)Raison d'Etre, Chemistry, and Some PhysiologyBlut ist ein ganz besondrer Saft

The mechanisms by which hyperbaric oxygen and carbogen improve tumour oxygenation

Feasibility of lung cancer hyperthermia using breathable perfluorochemical (PFC) liquids. Part I: Convective hyperthermia

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