TY - JOUR
T1 - Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma
AU - Worth, Laura L.
AU - Jaffe, Norman
AU - Benjamin, Robert S.
AU - Papadopoulos, Nicholas E.
AU - Patel, Shreyaskar
AU - Raymond, A. Kevin
AU - Jia, Shu Fang
AU - Rodriguez, Carlos
AU - Gano, Jacalyn
AU - Gianan, Mary Ann
AU - Kleinerman, Eugenie S.
PY - 1997/10
Y1 - 1997/10
N2 - A Phase II trial using interleukin 1α (IL-1α) and etoposide for patients with relapsed osteosarcoma (OS) was undertaken to assess the feasibility and tolerability of combination therapy with biotherapy and chemotherapy. Nine patients with histologically proven relapsed OS were treated with IL-1α immediately followed by etoposide daily for 5 days every 3 weeks. Surgical resection of lung metastasis or peripheral tumor was performed after two or three cycles. We observed three partial responses; disease was stable in another case. One case could not be evaluated. The side effects associated with combination therapy were as predicted from known side effects of the individual agents; however, more profound neutropenia was observed. Four patients exhibited clinical signs of capillary leak syndrome, i.e., hypotension, edema, and weight gain. The etiology of the capillary leak was unclear, because serum IL-1α, IL-2, tumor necrosis factor, and nitric oxide levels could not be used to predict which patients would develop capillary leak. Histological analysis of tumor specimens obtained after two or more courses of therapy showed changes consistent with a response to a biological response modifier: peripheral fibrosis surrounded the metastasis with infiltration of chronic and acute inflammatory cells. Because the response of relapsed OS to any type of salvage regimen has been poor, we interpret the clinical response of this therapy as good. However, the significant side effects associated with this therapy must also be taken into consideration before deciding to use this combination therapy. It is unfortunate that the study was stopped early due to halted production of IL- 1α. If this agent is again manufactured for clinical use, we conclude that additional evaluation in patients with relapsed OS is warranted.
AB - A Phase II trial using interleukin 1α (IL-1α) and etoposide for patients with relapsed osteosarcoma (OS) was undertaken to assess the feasibility and tolerability of combination therapy with biotherapy and chemotherapy. Nine patients with histologically proven relapsed OS were treated with IL-1α immediately followed by etoposide daily for 5 days every 3 weeks. Surgical resection of lung metastasis or peripheral tumor was performed after two or three cycles. We observed three partial responses; disease was stable in another case. One case could not be evaluated. The side effects associated with combination therapy were as predicted from known side effects of the individual agents; however, more profound neutropenia was observed. Four patients exhibited clinical signs of capillary leak syndrome, i.e., hypotension, edema, and weight gain. The etiology of the capillary leak was unclear, because serum IL-1α, IL-2, tumor necrosis factor, and nitric oxide levels could not be used to predict which patients would develop capillary leak. Histological analysis of tumor specimens obtained after two or more courses of therapy showed changes consistent with a response to a biological response modifier: peripheral fibrosis surrounded the metastasis with infiltration of chronic and acute inflammatory cells. Because the response of relapsed OS to any type of salvage regimen has been poor, we interpret the clinical response of this therapy as good. However, the significant side effects associated with this therapy must also be taken into consideration before deciding to use this combination therapy. It is unfortunate that the study was stopped early due to halted production of IL- 1α. If this agent is again manufactured for clinical use, we conclude that additional evaluation in patients with relapsed OS is warranted.
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M3 - Article
C2 - 9815556
AN - SCOPUS:0030844897
SN - 1078-0432
VL - 3
SP - 1721
EP - 1729
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 10
ER -