EVALUATION OF HYPERBARIC-OXYGEN AS A CHEMOSENSITIZER IN THE TREATMENTOF EPITHELIAL OVARIAN-CANCER IN XENOGRAFTS IN MICE

Background. Resistance to chemotherapy is common in bulky hypoxic tumo rs such as epithelial ovarian cancer. Hyperbaric oxygen (HBO) oxygenat es hypoxic tissues and promotes neovascularization. These unique prope rties of HBO may help overcome chemotherapy resistance by increasing b oth tumor perfusion and cellular sensitivity. This study was undertake n to determine if HBO increases the response of epithelial ovarian can cer to cisplatin chemotherapy. Methods. In Phase I, 64 nu/nu mice were divided into four groups and subcutaneously inoculated with cells fro m the A2780 human epithelial ovarian cancer cell line. Group 1 served as controls. Group 2 received weekly intraperitoneal cisplatin (3.15 m g/kg). Group 3 was exposed to HBO (dives) at 2.4 atmospheres absolute pressure for 90 minutes, 7 days a week. Group 4 received both cisplati n and HBO. In Phase II, 72 mice were divided into two groups and simil arly inoculated. Both groups received weekly intraperitoneal cisplatin (2.5 mg/kg). Group 1 was not exposed to HBO. Group 2 was exposed to H BO for 5 days a week. Results. Dramatic tumor neovascularization was f ound in tumors of mice exposed to HBO (P = 0.0001). There was signific ant (P = 0.014) tumor growth retardation in Phase I for mice receiving both cisplatin and HBO compared with those treated with cisplatin alo ne. This significance was noted after lust two doses of cisplatin but subsequently lost due to reduced numbers of mice. In Phase II, neovasc ularization was detectable after 10 HBO treatments (2 weeks) and was m aximal after 15 treatments (3 weeks). Conclusions. Hyperbaric oxygen i ncreases vascularity in bulky tumors such as epithelial ovarian cancer . There appears to be a relationship between increased vascularity and enhanced response to chemotherapy that merits further investigation.