Relation between limb toxicity and treatment outcomes after isolated limb perfusion for recurrent melanoma

Background: The optimal toxic reaction of the normal tissues in perfused li mbs after isolated limb perfusion (ILP) is unknown. Theoretically, more sev ere limb toxicity could reflect a concomitant increased toxic effect to the tumor and improved outcomes; We determined whether there is a relation bet ween limb toxicity and treatment outcomes after ILP for recurrent limb mela noma. Study Design: Among 252 patients with recurrent melanoma of the limbs, trea tment outcomes in 192 patients (76%) with no or mild acute limb toxicity we re compared with those in 60 (24%) with more severe reactions. Multivariate analysis was used to identify prognostic factors for complete response, li mb recurrence-free interval, and survival. Results: Among 112 patients with measurable disease, 65 patients (58%) had a complete response and 27 (42%) experienced a relapse in the perfused limb . For complete response,uninvolved regional lymph nodes (p = 0.0025) and IL P using tumor necrosis factor-alpha (p = 0.0076) appeared to be favorable p rognostic factors in multivariate analysis. There was no evidence of a rela tion between limb toxicity acid complete response either in univariate (p = 0.16) or multivariate analysis (p = 0.46). For limb recurrent-free interva l, only the number of lesions was a significant prognostic factor (p = 0.04 7); limb toxicity was not (p = 0.095), In 140 patients with recurrent melan oma excised before or at the moment of ILP, independent prognostic factors fbr survival were gender, the number of positive nodes, and stage of diseas e. There was no relation between limb toxicity and survival in either univa riate (p = 0.53) or multivariate analysis (p = 0.94). Forty-eight (34%) of the 140 patients had a relapse in the perfused limb. No prognostic factors for limb recurrent-free interval could be identified; limb toxicity was not related to relapse time in univariate or multivariate analyses (p = 0.16 a nd p = 0.14, respectively). Conclusions: More severe acute limb toxicity is not associated with improve d outcomes. One should aim at grade II toxicity (slight erythema or edema, compatible with complete recovery) at the most to increase the therapeutic ratio of ILP. (J Am Coll Surg 1999;188:522-530. (C) 1999 by the American Co llege of Surgeons).