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

Abstract

Fluosol®, a perfluorcarbon emulsion, has the ability to carry oxygen in solution. In conjunction with oxygen breathing and radiation, Fluosol® has been shown in animal models to enhance local tumor control. In September 1985, a Phase I/II Study was instituted to evaluate the effect of this adjuvant therapy with radiation in non small cell carcinoma of the luing. Fifty patients were enrolled in the study which was closed for accrual in November 1987. Five patients were withdrawn prior to the institution of radiation: one patient diagnosed with bone metastasis and four patients withdrawn due to mild to moderate reactions to Fluosole®. Of the 49 patients administered Fluosol®, 34 mild to moderate adverse reactions were noted in 22 patients to either the test dose/infusion (16 reactions including the withdrawn patients) or post infusion (18). Flushing, dyspnea and hypertension (test dose/infusion) and chills and/or fever (postinfusion) were the typical symptoms. Transient elevation of blood chemistries (SGOT, SGPT, alkaline phosphatase, BUN) were noted in some patients. Six patients had transient depression of WBC counts patients had transient depression of WBC counts (toxicity scores of 1 or 2) and two patients had transient depression of platelets (toxicity score of 1). None of these altered treatment. Forty-five patients received Fluosol® of which 34 completed the planned therapy. Six patients were diangosed with metastatic disease during therapy and three patients died of their disease during treatment. One patient was withdrawn due to ineligibility and one patient withdrawn due to moderate reactions to Fluosol® during the 3rd and 4th infusions. The total dose of Fluosol® was escalated from 42 mL/Kg to 49 mL/Kg in 5, 6, or 7 weekly infusions. Patients breathed 100% oxygen for a minimum of one-half hr prior to and during radiation treatment. Radiation therapy was administered at a daily thection of 165 to 200 cGy per fraction to a total dose of 5940 to 6800 cGy. Seventeen of 34 patients (50%) achieved a complete response to treatment Seventeen of 34 patients (50%) achieved a complete response to treatment and 11 patients (32%) had a partial response. Thirteen patients remeain alive (range of 12 to 20 months)_including 10 to 17 complete responders, 2 of 11 partial responders, and 1 treated with chemotherapy postradiation. The median absolute survival time of the patients completing therapy was 15.5 months and the 12 and 18 month absolute survival rats were 81% and 74%, respectively. The 45 patients starting protocol therapy had a median absolute survival of 9.2 months with a 12-months month and 18-month survival of 45% and 35%, respectively. Based on the results of this study further investigation of Fluosol® in the treatment of non small cell carcinoma of the of the lung is warranted.