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

Based on experimental and clinical evidence indicating that the anti-o xidant agent liposomal Cu/Zn superoxide dismutase (Lipsod) is an effec tive anti-inflammatory drug and possibly might be effective in reducin g late radiation-induced tissue injury, a clinical trial using Lipsod to treat long-standing radiation-induced fibrosis (RIF) was begun at t he Necker Hospital, Paris in May 1984. Thirty-four patients presenting 42 distinct palpable zones of RIF involving the skin and underlying t issues 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 physician s at each check-up. Parameters noted included determination of the den sity of the palpated fibrotic block and the dimensions of the projecte d cutaneous surface. The extent of change in the fibrotic zone was exp ressed 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 b efore and after treatment. Changes in density were noted and scored. A ll patients showed some clinical regression of fibrosis. In most patie nts, clinically assessable regression begun during the third week of t reatment 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 t he area of the cutaneous surface was scored satisfactory (34-66%) to e xcellent (67-100%) in 79% of the fibrotic zones. A complete response w as observed in seven fibrotic zones (17%). Softening was significant t o pronounced in 86% of the fibrotic zones. The stability of the respon se (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 u nder clinical conditions.