A Phase Ib/II trial of granulocyte-macrophage−colony stimulating factor and interleukin-2 for renal cell carcinoma patients with pulmonary metastases : A case of fatal central nervous system thrombosis
✍ Scribed by Kirsten M. Hotton; Masoud Khorsand; Jacquelyn A. Hank; Mark Albertini; Kyung Mann Kim; George Wilding; M. Shahriar Salamat; Marilyn Larson; Paul Sondel; Joan H. Schiller
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 187 KB
- Volume
- 88
- Category
- Article
- ISSN
- 0008-543X
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✦ Synopsis
BACKGROUND.
Interleukin-2 (IL-2) and granulocyte-macrophageϪcolony 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 ϫ 10 6 IU/m 2 /day 96-hour continuous infusion IL-2 on Days 1Ϫ4, 8Ϫ11, and 15Ϫ18, and 1.25, 2.25, or 2.5 g/kg/day GM-CSF on Days 8Ϫ19.
RESULTS.
Sixteen patients were treated per protocol, 14 of whom could be evaluated for disease progression. None of these 14 patients had Ͼ50% 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.