Ll. Worth et al., PHASE-II STUDY OF RECOMBINANT INTERLEUKIN-1-ALPHA AND ETOPOSIDE IN PATIENTS WITH RELAPSED OSTEOSARCOMA, Clinical cancer research, 3(10), 1997, pp. 1721-1729
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.