A phase I study of subcutaneous recombinant interleukin-2 and interferon alfa-2a.
BACKGROUND
Both recombinant interferon alfa and interleukin-2 (IL-2) have been shown to have some activity as single agents in metastatic renal cell cancer (RCC), although their activity is minimal in more common solid tumors. Recent preclinical studies have suggested that the combination of these two agents is especially promising.


METHODS
Subcutaneous recombinant interferon alfa-2a and IL-2 were administered at one of five dose levels to 33 patients with refractory solid tumors, including 21 patients with RCC. A constant ratio of 5:1 of interferon alfa-2a to IL-2 was used. Interferon alfa-2a and IL-2 were administered three and five times weekly, respectively, for a total of 4 weeks, followed by a rest of 1-3 weeks between cycles.


RESULTS
The dose-limiting toxic effects included hypotension, nephrotoxicity, and fatigue. At the recommended Phase II dose of 7.5 million units (MU)/m2 of interferon alfa-2a and 1.5 MU/m2 of IL-2, 12 patients were treated. Ten of 12 completed the 4-week cycle without modification. Four patients at that dose level had Grade 3-4 toxic effects. Partial responses were observed in 4 of 16 assessable patients with RCC.


CONCLUSIONS
Subcutaneous interferon alfa-2a and IL-2 can be self-administered safely on an outpatient basis. At tolerable doses, responses can be achieved in metastatic RCC.
Ratain
M J
MJ
Department of Medicine, University Chicago Pritzker School of Medicine, Illinois.
Priest
E R
ER
Janisch
L
L
Vogelzang
N J
NJ
D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D007376:Interleukin-2 / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011994:Recombinant Proteins / Q000008:administration & dosage
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D007376:Interleukin-2; D011994:Recombinant Proteins