Renal toxicity of interleukin-2 administration in patients with metastatic renal cell cancer: effect of pre-therapy nephrectomy.
Systemic administration of interleukin-2 and lymphokine-activated killer cells is a new approach to the immunotherapy of advanced cancer. Metastatic renal cell cancer is one of the histological types of tumors particularly susceptible to this treatment approach although renal toxicity often is a dose-limiting side effect. We compared the renal functional changes observed during interleukin-2 therapy in 52 consecutive patients with advanced renal cancer to that of 83 consecutive patients with metastatic nonrenal cancer. Of the 52 patients with renal cancer 41 had recently undergone nephrectomy. The over-all peak serum creatinine values and the percentage increase of serum creatinine over baseline for all patients studied were significantly higher in cycle 2 of interleukin-2 therapy than in cycle 1: 3.8 +/- 0.2 versus 2.6 +/- 0.1 mg. per dl. and 241.7 +/- 16.5 versus 140.3 +/- 11.0 per cent, respectively. In patients with pre-therapy serum creatinine values of 0.4 to 0.9 mg. per dl. there were no significant differences in the mean peak serum creatinine nor in the percentage increase over baseline between renal and nonrenal cancer patients during cycle 1. In cycle 2 of therapy these values were higher in the renal cancer group (3.6 +/- 0.8 versus 2.4 +/- 0.2 mg. per dl. and 310.4 +/- 103.5 versus 214 +/- 30.4 per cent, respectively) but they did not reach statistical significance (P2 = 0.08 and 0.25, respectively). Renal and nonrenal cancer patients with pre-therapy serum creatinine levels of 1.0 to 1.4 mg. per dl. achieved similar high values in cycle 2 of interleukin-2 therapy (3.9 +/- 0.3 versus 3.9 +/- 0.4 mg. per dl. and 222.7 +/- 23.2 versus 248.7 +/- 33.5 per cent, respectively), although the initial increase (cycle 1) was higher in the renal cancer patients (3.3 +/- 0.3 versus 2.4 +/- 0.2 mg. per dl. and 172.3 +/- 25.9 versus 116.1 +/- 18.0 per cent, respectively). Baseline serum creatinine greater than or equal to 1.5 mg. per dl. was associated with an over-all higher peak serum creatinine and higher percentage increase of serum creatinine over baseline than that below 1.5 mg. per dl. baseline: 4.4 mg.per dl. and 171.1 +/- 36.3 per cent in cycle 1 and 6.5 +/- 0.7 mg. per dl. and 296.1 +/- 44.0 per cent in cycle 2, respectively (p less than 0.01). There was no association between peak serum creatinine and interval from nephrectomy to interleukin-2 therapy.(ABSTRACT TRUNCATED AT 400 WORDS)
Belldegrun
A
A
Surgery Branch, National Cancer Institute, Bethesda, Maryland.
Webb
D E
DE
Austin
H A
HA
Steinberg
S M
SM
Linehan
W M
WM
Rosenberg
S A
SA
D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003404:Creatinine / Q000097:blood; D005260:Female; D006801:Humans; D007116:Immunization, Passive; D007376:Interleukin-2 / Q000009:adverse effects* / Q000627:therapeutic use; D007668:Kidney / Q000503:physiopathology*; D007680:Kidney Neoplasms / Q000628:therapy*; D007694:Killer Cells, Natural / Q000637:transplantation; D008222:Lymphokines / Q000276:immunology; D008297:Male; D009392:Nephrectomy; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012307:Risk Factors
D007376:Interleukin-2; D008222:Lymphokines; D011994:Recombinant Proteins; D003404:Creatinine