PHASE-II STUDY OF RECOMBINANT INTERLEUKIN-1-ALPHA AND ETOPOSIDE IN PATIENTS WITH RELAPSED OSTEOSARCOMA

A Phase II trial using interleukin 1 alpha (IL-1 alpha) and etoposide for patients with relapsed osteosarcoma (OS) was undertaken to assess the feasibility and tolerability of combination therapy with biotherap y and chemotherapy, Nine patients with histologically proven relapsed OS were treated with IL-1 alpha immediately followed by etoposide dail y for 5 days every 3 weeks, Surgical resection of lung metastasis or p eripheral tumor was performed after two or three cycles, We observed t hree partial responses; disease was stable in another case, One case c ould not be evaluated, The side effects associated with combination th erapy were as predicted from known side effects of the individual agen ts; however, more profound neutropenia was observed, Four patients exh ibited clinical signs of capillary leak syndrome, i,e,, hypotension, e dema, and weight gain, The etiology of the capillary leak was unclear, because serum IL-1 alpha, IL-2, tumor necrosis factor, and nitric oxi de levels could not be used to predict which patients would develop ca pillary leak, Histological analysis of tumor specimens obtained after two or more courses of therapy showed changes consistent with a respon se to a biological response modifier: peripheral fibrosis surrounded t he metastasis with infiltration of chronic and acute inflammatory cell s, Because the response of relapsed OS to any type of salvage regimen has been poor, we interpret the clinical response of this therapy as g ood, However, the significant side effects associated with this therap y must also be taken into consideration before deciding to use this co mbination therapy, It is unfortunate that the study was stopped early due to halted production of IL-1 alpha, If this agent is again manufac tured for clinical use, we conclude that additional evaluation in pati ents with relapsed OS is warranted.