Lack of complications in long-term survivors after treatment with Fluosol and oxygen as an adjuvant to radiation therapy for high-grade brain tumors.

PURPOSE: A Phase I/II trial was initiated in 1987 to determine the toxicity/efficacy of the perfluorochemical emulsion Fluosol-DA 20% and 100% oxygen as an adjuvant to conventional radiation therapy for high-grade brain tumors. METHODS AND MATERIALS: Three grade 3 and 15 grade 4 patients received 1 Fluosol administration (8 mL/kg) per week with daily oxygen breathing prior to and during radiation therapy. Megavoltage radiation was delivered to the whole brain at 25 x 1.8 Gy, followed by 10 x 2 Gy to a boost volume, resulting in a total tumor bed dose of 65 Gy in 7 weeks. RESULTS: Of the 18 patients, 10 (nine grade 4, one grade 3) survived more than 1 year postsurgery, six (all grade 4) lived more than 2 years, four of these patients lived more than 3 years, and three patients are alive at times ranging from 250 to 276 weeks. The median survival of the Fluosol group was 75 weeks, not statistically different from 54 weeks for a historical, matched control group. However, a Gehan-Wilcoxon test applied to those patients that survived > 1 year revealed a significant difference (p = 0.0013) in favor of the Fluosol group. Periodic clinical evaluations showed no evidence of any functional or neurological defects that could be attributed to radiation therapy and/or Fluosol. Radiographic studies (computed tomography and magnetic resonance imaging) revealed no structural alterations outside the original tumor volume, and changes within the tumor region were easily assignable to expected effects of tumor, surgery, or radiation alone. CONCLUSION: These results indicate that, although Fluosol/oxygen added to conventional radiation therapy does not enhance survival of patients who succumb to their disease early, it does confer a significant benefit to patients that survive past 1 year. The minimal acute side effects and no long-term deleterious effects suggest that Fluosol/oxygen sensitizes only hypoxic cells, with no effect on well-oxygenated normal tissues within the brain. We have been impressed by the quality of life of the surviving patients following radiation therapy with adjuvant Fluosol+oxygen.