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A Phase Ib/II trial of granulocyte‐macrophage−colony stimulating factor and interleukin‐2 for renal cell carcinoma patients with pulmonary metastases
Author(s) -
Hotton Kirsten M.,
Khorsand Masoud,
Hank Jacquelyn A.,
Albertini Mark,
Kim Kyung Mann,
Wilding George,
Salamat M. Shahriar,
Larson Marilyn,
Sondel Paul,
Schiller Joan H.
Publication year - 2000
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/(sici)1097-0142(20000415)88:8<1892::aid-cncr19>3.0.co;2-2
Subject(s) - medicine , granulocyte macrophage colony stimulating factor , renal cell carcinoma , granulocyte , cancer research , macrophage , oncology , cytokine , in vitro , biochemistry , biology
BACKGROUND Interleukin‐2 (IL‐2) and granulocyte‐macrophage−colony stimulating factor (GM‐CSF) are cytokines with nonoverlapping pleiotropic effects. In a prior Phase Ib study, this combination of agents exhibited antitumor effects in the lungs of four of eight patients with renal cell carcinoma and pulmonary metastases. We conducted this Phase Ib/II trial to determine the response rate of renal cell carcinoma patients with pulmonary metastases treated with continuous infusion IL‐2 plus GM‐CSF. METHODS Patients with renal cell carcinoma and pulmonary metastases were treated with 1.5, 2.25, or 4.5 × 10 6 IU/m 2 /day 96‐hour continuous infusion IL‐2 on Days 1−4, 8−11, and 15−18, and 1.25, 2.25, or 2.5 μg/kg/day GM‐CSF on Days 8−19. RESULTS Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had >50% shrinkage of either total tumor burden or pulmonary metastasis. One patient developed Grade 5 neurotoxicity. Autopsy revealed acute multifocal cerebral venous thrombosis as well as acute subdural and subarachnoid hemorrhage. CONCLUSIONS The combination of IL‐2 and GM‐CSF may be associated with marked morbidity and, as in one case in this study, mortality. No significant antitumor activity was appreciated. Thus, the combination of IL‐2 and GM‐CSF, when administered at this dose and according to this schedule, does not appear to be active in renal cell carcinoma and is associated with significant toxicities. Further studies using this combination of agents should only be undertaken with extreme caution and particular attention to neurotoxicity. Cancer 2000;88:1892–901. © 2000 American Cancer Society.