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Thompson JA, Shulman KL, Benyunes MC, et al. Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma. J Clin Oncol. 1992;10(6):960-8doi: 10.1200/JCO.1992.10.6.960.
Thompson, J. A., Shulman, K. L., Benyunes, M. C., Lindgren, C. G., Collins, C., Lange, P. H., Bush, W. H., Benz, L. A., & Fefer, A. (1992). Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma. Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 10(6), 960-8. https://doi.org/10.1200/JCO.1992.10.6.960
Thompson, J A, et al. "Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma." Journal of clinical oncology : official journal of the American Society of Clinical Oncology vol. 10,6 (1992): 960-8. doi: https://doi.org/10.1200/JCO.1992.10.6.960
Thompson JA, Shulman KL, Benyunes MC, Lindgren CG, Collins C, Lange PH, Bush WH, Benz LA, Fefer A. Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma. J Clin Oncol. 1992 Jun;10(6):960-8. doi: 10.1200/JCO.1992.10.6.960. PMID: 1588376.
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J Clin Oncol. 1992 Jun;10(6):960-8. doi: 10.1200/JCO.1992.10.6.960.

Prolonged continuous intravenous infusion interleukin-2 and lymphokine-activated killer-cell therapy for metastatic renal cell carcinoma.

Journal of clinical oncology : official journal of the American Society of Clinical Oncology

J A Thompson, K L Shulman, M C Benyunes, C G Lindgren, C Collins, P H Lange, W H Bush, L A Benz, A Fefer

Affiliations

  1. Department of Medicine, University of Washington School of Medicine, Seattle.

PMID: 1588376 DOI: 10.1200/JCO.1992.10.6.960

Abstract

PURPOSE: Two consecutive protocols of continuous intravenous (CIV) infusion interleukin-2 (IL-2) and lymphokine-activated killer (LAK) cells were carried out in patients with metastatic renal cell carcinoma (RCC) to determine the response rate and toxicity.

PATIENTS AND METHODS: In both protocols, patients received induction IL-2 at 6 x 10(6) U/m2/d on days 1 to 5, and underwent leukapheresis on days 7 to 9 at the peak of rebound lymphocytosis. LAK cells were generated by a 5-day incubation with IL-2 at 1,000 U/mL, and were infused on days 12 to 14. For the first 20 patients (protocol A), maintenance IL-2 was administered at 6 x 10(6) U/m2/d on days 12 to 16. On the assumption that less IL-2 might be required to maintain rather than to induce LAK activity, and that a longer duration of maintenance IL-2 might enhance LAK survival and function in vivo, the protocol for the subsequent 22 patients (protocol B) was altered so that the maintenance phase consisted of a lower dose of IL-2 (2 x 10(6) U/m2/d) administered for a longer period of time (days 10 to 20).

RESULTS: In protocol A, there were two complete responses (CRs) and three partial responses (PRs), for a total response rate of 25%. One PR was surgically converted into a CR. The durations of the CRs are 36+, 18+, and 18+ months. Hypotension and capillary leak were most severe during maintenance, which limited the median duration of maintenance IL-2 to 4 days. In protocol B, no patient experienced severe hypotension, and the median duration of maintenance IL-2 was 9 days. Two patients exhibited a CR and seven a PR, for a total response rate of 41%. Two PRs were surgically converted to CRs. The durations of CR are 14+, 9+, 6+, and 5+ months. In both protocols, the CIV induction regimen resulted in marked rebound lymphocytosis (mean, 11,097/microL) and LAK-cell yield (mean, 18.1 x 10(10)). The cumulative response rate was 14 of 42 patients, or 33% (95% confidence interval, 19% to 47%).

CONCLUSION: These results demonstrate that both protocols of CIV IL-2 plus LAK cells have substantial antitumor activity, and that a longer maintenance phase of IL-2 at a lower dose is associated with significantly less toxicity without a loss of therapeutic efficacy.

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