A pilot phase II trial of continuous-infusion interleukin-2 followed by lymphokine-activated killer cell therapy and bolus-infusion interleukin-2 in renal cancer.
Nine patients with metastatic renal cell carcinoma were entered into a pilot protocol including a 4-week regimen utilizing human recombinant interleukin-2 (IL-2) and in vitro lymphokine-activated killer (LAK) cells. The regimen included 2 weeks (4 days of treatment and 3 days of rest/week) of continuous-infusion (c.i.) IL-2 at 3 x 10(6) U/m2/day, followed by two leukaphereses. LAK cells were cultured in vitro for 48 to 72 h and administered as a single infusion, followed by 9 days of bolus i.v. injections of 10(6) U IL-2/m2/dose, given every 8 hours (t.i.d.). The average (+/- SD) number of LAK cells infused per patient was 7.2 x 10(10) (+/- 3.5 x 10(10)). One patient showed > 50% shrinkage of tumor (lung + renal bed recurrence). Toxicity was similar to that encountered in other studies using similar IL-2 doses and LAK cells and consisted of fever, hypotension, fluid retention, and reversible renal insufficiency. These results indicate that the 2 weeks of IL-2 c.i. provided conditions enabling the harvest of large quantities of mononuclear cells from the peripheral blood of patients; this could be useful for future trials requiring the use of in vitro activated lymphocytes. Nevertheless, these pilot data suggest that this regimen of prolonged t.i.d. IL-2 administration after the LAK infusion does not seem to generate any improvement in antitumor effects from those obtained using other LAK + IL-2 regimens.
Gambacorti-Passerini
C
C
Department of Human Oncology, University of Wisconsin, Madison.
Hank
J A
JA
Albertini
M R
MR
Borchert
A A
AA
Moore
K H
KH
Schiller
J H
JH
Bechhofer
R
R
Borden
E C
EC
Storer
B
B
Sondel
P M
PM
D000328:Adult; D002292:Carcinoma, Renal Cell / Q000628:therapy*; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D007680:Kidney Neoplasms / Q000628:therapy*; D015979:Killer Cells, Lymphokine-Activated; D007937:Leukapheresis; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use; D012074:Remission Induction
D007376:Interleukin-2; D011994:Recombinant Proteins