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


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%).


CONCLUSIONS
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.
Thompson
J A
JA
Department of Medicine, University of Washington School of Medicine, Seattle.
Shulman
K L
KL
Benyunes
M C
MC
Lindgren
C G
CG
Collins
C
C
Lange
P H
PH
Bush
W H
WH
Benz
L A
LA
Fefer
A
A
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000000981:diagnostic imaging / Q000276:immunology / Q000556:secondary* / Q000628:therapy; D005260:Female; D006801:Humans; D016219:Immunotherapy, Adoptive / Q000009:adverse effects; D007262:Infusions, Intravenous; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000009:adverse effects; D007680:Kidney Neoplasms / Q000276:immunology / Q000473:pathology*; D015979:Killer Cells, Lymphokine-Activated; D008297:Male; D008875:Middle Aged; D011859:Radiography
D007376:Interleukin-2