PEG-hemoglobin: effects on tumor oxygenation and response to chemotherapy.
BACKGROUND
The study was undertaken to determine whether administration of PEG-hemoglobin could improve the oxygenation of a solid tumor prior to and after chemotherapy and to determine whether administration of PEG-hemoglobin could enhance the efficacy of chemotherapy in a solid tumor.


METHODS
Rats bearing the 13762 mammary carcinoma were untreated or treated with cyclophosphamide, melphalan, taxol or cisplatin. Tumor oxygenation was determined 24 hrs. after chemotherapy with or without administration of PEG-hemoglobin while the animals breathed air, 28% oxygen or carbogen. Mice bearing the EMT-6 murine mammary carcinoma were treated with single doses of chemotherapy with or without co-administration of PEG-hemoglobin and tumor cell and bone marrow CFU-GM survivals were determined. Other EMT-6 tumor-bearing mice were treated with multiple doses of chemotherapy with or without PEG-hemoglobin and tumor growth delay was determined.


RESULTS
Administration of PEG-hemoglobin was effective in decreasing hypoxia in the 13762 mammary carcinoma both prior to and after chemotherapy administration. Increasing the level of inspired oxygen further decreased the tumor hypoxia most effectively when the level of tumor cell killing by the chemotherapy was high. Administration of PEG-hemoglobin along with air breathing to mice bearing the EMT-6 tumor increased tumor cell killing by cyclophosphamide, BCNU, adriamycin and taxol without increasing toxicity to the bone marrow CFU-GM. PEG-Hemoglobin given prior to each dose of chemotherapy increased the tumor growth delay produced by cyclophosphamide, adriamycin, 5-fluorouracil, BCNU and taxol in a manner with increased level of inspired oxygen and with a concomitant decreased in lung metastases.


CONCLUSIONS
Further investigation of PEG-hemoglobin as an oxygen delivery agent in oncology is warranted.
Teicher
B A
BA
Dana-Farber Cancer Institute and Joint Center for Radiation Therapy, Boston, MA 02115, USA. beverly_teicher@dfci.harvard.edu
Ara
G
G
Herbst
R
R
Takeuchi
H
H
Keyes
S
S
Northey
D
D
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001802:Blood Substitutes / Q000494:pharmacology; D016190:Carboplatin / Q000494:pharmacology; D002277:Carcinoma / Q000188:drug therapy* / Q000378:metabolism; D003520:Cyclophosphamide / Q000494:pharmacology; D004334:Drug Administration Schedule; D005260:Female; D006454:Hemoglobins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000556:secondary; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D008558:Melphalan / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D010100:Oxygen / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D017239:Paclitaxel / Q000494:pharmacology; D011092:Polyethylene Glycols / Q000494:pharmacology*; D051381:Rats; D011916:Rats, Inbred F344
D000970:Antineoplastic Agents; D001802:Blood Substitutes; D006454:Hemoglobins; C050907:pyridoxalated-hemoglobin-polyethylene glycol conjugate; D011092:Polyethylene Glycols; D003520:Cyclophosphamide; D016190:Carboplatin; D017239:Paclitaxel; D008558:Melphalan; D010100:Oxygen