Phase I/II trial of subcutaneous interleukin-2, granulocyte-macrophage colony-stimulating factor and interferon-α in patients with metastatic renal cell carcinoma.
OBJECTIVE
To determine, in a phase I/II trial, the maximum tolerated dose (MTD), clinical activity and safety of concurrent subcutaneous (s.c.) interleukin-2 (IL-2), interferon-α2b (IFN-α) and granulocyte-macrophage colony-stimulating factor (GM-CSF).


METHODS
Patients with metastatic renal cell carcinoma (RCC) received on a 3+3 trial design escalating doses of s.c. GM-CSF, IL-2 and IFN-α. Dose-limiting toxicities (DLTs) during the first 6-week cycle were used to determine the MTD. A phase II trial was then initiated to determine clinical activity.


RESULTS
A total of sixty patients were enrolled in the study (phase I = 31; phase II = 29). Two DLTs were observed (G3 nausea/vomiting and fatigue) and the MTD was determined to be GM-CSF 5.0 µg/kg/day, IL-2 9.0 mIU/m(2)/day and IFN-α 5.0 mU/m(2)/day. Patients received a median (range) of four (one to 11) cycles of therapy. G3 adverse events were reported in 10 of 31 (32%) patients. The overall response rate was 20% (one complete response and 11 partial responses), including patients who were rendered free of disease with surgery. The median progression-free survival and overall survival were 6.0 and 23.4 months, respectively.


CONCLUSIONS
Immunotherapy with concurrent s.c. GM-CSF, IL-2 and IFN-α is generally well tolerated. The overall response rate observed with this combination continues to show the efficacy of immunotherapy in a selected group of metastatic RCC patients.
Division of Solid Tumor Oncology, Cleveland Clinic Taussig Cancer Center and Glickman Urological and Kidney Institute, Cleveland, OH 44195, USA. garciaj4@ccf.org
Jorge A
JA
Garcia
Tarek
T
Mekhail
Paul
P
Elson
Laura
L
Wood
Ronald M
RM
Bukowski
Robert
R
Dreicer
Brian I
BI
Rini
D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000188:drug therapy* / Q000556:secondary; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000008:administration & dosage*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D007279:Injections, Subcutaneous; D016898:Interferon-alpha / Q000008:administration & dosage*; D007376:Interleukin-2 / Q000008:administration & dosage*; D007680:Kidney Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D014481:United States / Q000453:epidemiology
D007155:Immunologic Factors; D016898:Interferon-alpha; D007376:Interleukin-2; D016178:Granulocyte-Macrophage Colony-Stimulating Factor