Outpatient subcutaneous interleukin-2 and interferon-alpha for metastatic renal cell cancer: five-year follow-up of the Cytokine Working Group Study.
OBJECTIVE
A phase II trial of outpatient subcutaneous (SC) interleukin-2 (rIL-2) plus interferon-alpha (IFN-alpha 2B) was performed in patients with metastatic renal cell cancer. A 5-year follow-up of that Cytokine Working Group study is presented.


METHODS
Forty-seven patients meeting eligibility criteria of previous Cytokine Working Group studies were treated on an outpatient basis with SC rIL-2 (Chiron, Emeryville, CA), 5 x 10(6) IU/m2/dose q 8 hr x 3, then daily, 5 days per week, and IFN-alpha 2B (Schering-Plough, Kenilworth, NJ), 5 x 10(6) IU/m2/dose three times weekly for 4 weeks. After a 2- to 4-week break, patients were scheduled to continue treatment for up to six cycles.


RESULTS
There were two complete and six partial responders (17% response rate, 95% CI: 8%-31%). Median duration of response was 12 months (range 1-49+ months), with complete responses of 15 and 49+ months. Responding sites of disease included lung, nodes, soft tissue, bone, and liver. Dose and schedule were adjusted to control toxicity at grade 2/3 levels, with 50% requiring dosage alterations. Grade 2/3 toxicity included fatigue, nausea/vomiting, diarrhea, anorexia, fluid overload, rash, CNS, injection site pain, chest pain/palpitations (including atrial fibrillation requiring treatment, two patients), and hypotension. Grade 4 toxicity included dehydration (seven patients), vomiting (one patient), and irreversible renal failure with crescentic glomerulonephritis requiring dialysis (one patient).


CONCLUSIONS
SC rIL-2 plus IFN-a2B is tolerated in the outpatient setting with frequent dose adjustments. The overall response rate of this regimen is similar to that seen with high-dose rIL-2 alone; however, the response duration appears to be shorter.
Dutcher
J P
JP
Albert Einstein Cancer Center/Montefiore Medical Center, Bronx, New York, USA.
Fisher
R I
RI
Weiss
G
G
Aronson
F
F
Margolin
K
K
Louie
A
A
Mier
J
J
Caliendo
G
G
Sosman
J A
JA
Eckardt
J R
JR
Ernest
M L
ML
Doroshow
J
J
Atkins
M
M
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use* / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007376:Interleukin-2 / Q000627:therapeutic use* / Q000633:toxicity; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000556:secondary; D008297:Male; D008875:Middle Aged; D011994:Recombinant Proteins / Q000627:therapeutic use / Q000633:toxicity; D016896:Treatment Outcome
D016207:Cytokines; D007376:Interleukin-2; D011994:Recombinant Proteins