SUCCESSFUL TREATMENT OF RADIATION-INDUCED FIBROSIS USING LIPOSOMAL CU/ZN SUPEROXIDE-DISMUTASE - CLINICAL-TRIAL

Based on experimental and clinical evidence indicating that the anti-oxidant agent liposomal Cu/Zn superoxide dismutase (Lipsod) is an effective anti-inflammatory drug and possibly might be effective in reducing late radiation-induced tissue injury, a clinical trial using Lipsod to treat long-standing radiation-induced fibrosis (RIF) was begun at the Necker Hospital, Paris in May 1984. Thirty-four patients presenting 42 distinct palpable zones of RIF involving the skin and underlying tissues were treated from May 1984 to January 1986 and followed for an average of 5 years (range, 14-89 months). Lipsod was administered over 3 weeks in twice weekly i.m. injections of 5 mg for a total of 30 mg. Patients underwent two physical examinations by independent physicians at each check-up. Parameters noted included determination of the density of the palpated fibrotic block and the dimensions of the projected cutaneous surface. The extent of change in the fibrotic zone was expressed as the ratio of the sum of the dimensions (L + W) and the ratio of the uncorrected areas (L x W) of the projected cutaneous surface before and after treatment. Changes in density were noted and scored. All patients showed some clinical regression of fibrosis. In most patients, clinically assessable regression begun during the third week of treatment and was maximum by 2 months. The mean decreases in the linear dimensions (L + W) and in the area (L x W) of the projected cutaneous surface were 41 +/- 30% and 57 +/- 26%, respectively. Regression in the area of the cutaneous surface was scored satisfactory (34-66%) to excellent (67-100%) in 79% of the fibrotic zones. A complete response was observed in seven fibrotic zones (17%). Softening was significant to pronounced in 86% of the fibrotic zones. The stability of the response (actuarial method) was 95% at 3 years and 70% at 5 years. Treatment was well tolerated. To our knowledge, Lipsod is the first agent shown to be effective in reducing long-standing post-irradiation fibrosis under clinical conditions.