Phase II study of recombinant interleukin 1alpha and etoposide in patients with relapsed osteosarcoma.
A Phase II trial using interleukin 1alpha (IL-1alpha) 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-1alpha 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-1alpha, 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-1alpha. If this agent is again manufactured for clinical use, we conclude that additional evaluation in patients with relapsed OS is warranted.
Worth
L L
LL
Departments of Pediatrics, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Jaffe
N
N
Benjamin
R S
RS
Papadopoulos
N E
NE
Patel
S
S
Raymond
A K
AK
Jia
S F
SF
Rodriguez
C
C
Gano
J
J
Gianan
M A
MA
Kleinerman
E S
ES
D000293:Adolescent; D000328:Adult; D000505:Alopecia / Q000139:chemically induced; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001855:Bone Marrow Diseases / Q000139:chemically induced; D001859:Bone Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000628:therapy*; D019559:Capillary Leak Syndrome / Q000139:chemically induced; D003131:Combined Modality Therapy; D016207:Cytokines / Q000097:blood; D004357:Drug Synergism; D005047:Etoposide / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D005240:Feasibility Studies; D005260:Female; D005266:Femoral Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000601:surgery / Q000628:therapy; D005334:Fever / Q000139:chemically induced; D005355:Fibrosis; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D007022:Hypotension / Q000139:chemically induced; D007155:Immunologic Factors / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D007375:Interleukin-1 / Q000009:adverse effects / Q000494:pharmacology / Q000600:supply & distribution / Q000627:therapeutic use*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy; D008297:Male; D009503:Neutropenia / Q000139:chemically induced; D012516:Osteosarcoma / Q000188:drug therapy / Q000473:pathology / Q000556:secondary / Q000601:surgery / Q000628:therapy*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000494:pharmacology / Q000600:supply & distribution / Q000627:therapeutic use; D012074:Remission Induction; D012120:Respiration Disorders / Q000139:chemically induced; D016879:Salvage Therapy; D016896:Treatment Outcome
D000972:Antineoplastic Agents, Phytogenic; D016207:Cytokines; D007155:Immunologic Factors; D007375:Interleukin-1; D011994:Recombinant Proteins; D005047:Etoposide