Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma

Laura L. Worth, Norman Jaffe, Robert S. Benjamin, Nicholas E. Papadopoulos, Shreyaskar Patel, A. Kevin Raymond, Shu Fang Jia, Carlos Rodriguez, Jacalyn Gano, Mary Ann Gianan, Eugenie S. Kleinerman

Research output: Contribution to journalArticle

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)1721-1729
Number of pages9
JournalClinical Cancer Research
Volume3
Issue number10
StatePublished - Oct 1997
Externally publishedYes

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Etoposide
Osteosarcoma
Interleukin-1
Capillary Leak Syndrome
Therapeutics
Neoplasm Metastasis
Biological Therapy
Immunologic Factors
Neutropenia
Hypotension
Weight Gain
Interleukin-2
Edema
Neoplasms
Nitric Oxide
Fibrosis
Tumor Necrosis Factor-alpha
Drug Therapy
Lung
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Worth, L. L., Jaffe, N., Benjamin, R. S., Papadopoulos, N. E., Patel, S., Raymond, A. K., ... Kleinerman, E. S. (1997). Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma. Clinical Cancer Research, 3(10), 1721-1729.

Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma. / Worth, Laura L.; Jaffe, Norman; Benjamin, Robert S.; Papadopoulos, Nicholas E.; Patel, Shreyaskar; Raymond, A. Kevin; Jia, Shu Fang; Rodriguez, Carlos; Gano, Jacalyn; Gianan, Mary Ann; Kleinerman, Eugenie S.

In: Clinical Cancer Research, Vol. 3, No. 10, 10.1997, p. 1721-1729.

Research output: Contribution to journalArticle

Worth, LL, Jaffe, N, Benjamin, RS, Papadopoulos, NE, Patel, S, Raymond, AK, Jia, SF, Rodriguez, C, Gano, J, Gianan, MA & Kleinerman, ES 1997, 'Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma', Clinical Cancer Research, vol. 3, no. 10, pp. 1721-1729.
Worth LL, Jaffe N, Benjamin RS, Papadopoulos NE, Patel S, Raymond AK et al. Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma. Clinical Cancer Research. 1997 Oct;3(10):1721-1729.
Worth, Laura L. ; Jaffe, Norman ; Benjamin, Robert S. ; Papadopoulos, Nicholas E. ; Patel, Shreyaskar ; Raymond, A. Kevin ; Jia, Shu Fang ; Rodriguez, Carlos ; Gano, Jacalyn ; Gianan, Mary Ann ; Kleinerman, Eugenie S. / Phase II study of recombinant interleukin 1α and etoposide in patients with relapsed osteosarcoma. In: Clinical Cancer Research. 1997 ; Vol. 3, No. 10. pp. 1721-1729.
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