Phase II trial of branched peginterferon-alpha 2a (40 kDa) for patients with advanced renal cell carcinoma.
BACKGROUND
Peginterferon-alpha 2a (40 kDa), PEGASYS(TM) (PEG-IFN), is a modified form of recombinant human interferon (IFN)-alpha 2a with sustained absorption and prolonged half-life after subcutaneous administration. A phase II trial was conducted in previously untreated patients with advanced renal cell carcinoma (RCC) to assess efficacy, toxicity and pharmacokinetic profile.


METHODS
Forty previously untreated patients with advanced RCC were enrolled on this multicenter trial. The median age was 60 years and 63% had prior nephrectomy. PEG-IFN was administered at a dose of 450 micro g/week on a weekly basis by subcutaneous injection. Serial venous blood samples were drawn to assess concentrations of PEG-IFN.


RESULTS
Five (13%) patients achieved a major response (four partial and one complete). The median time to progression was 3.8 months, and 63% of patients were alive at 1 year. The toxicity profile was mostly mild to moderate in intensity. Toxicity higher than grade 2 included neutropenia (six patients), fatigue/asthenia (four patients), nausea/vomiting (three patients) and elevated hepatic transaminase concentrations (four patients). Serum drug levels were studied in all patients; mean C(max) at week 1 was 19 ng/ml, and levels were sustained at close to peak over 1 week. With chronic dosing, drug concentration was increased 3-fold, and steady state was achieved in 5-9 weeks.


CONCLUSIONS
The sustained maintenance of serum levels of PEG-IFN allows once-weekly dosing. The efficacy and tolerability profile was qualitatively similar to standard IFN-alpha, and adverse events were mostly mild to moderate in nature.
Motzer
R J
RJ
Memorial Sloan-Kettering Cancer Center, New York, NY 10021, USA. motzerr@mskcc.org
Rakhit
A
A
Thompson
J
J
Gurney
H
H
Selby
P
P
Figlin
R
R
Negrier
S
S
Ernst
S
S
Siebels
M
M
Ginsberg
M
M
Rittweger
K
K
Hooftman
L
L
D015088:2',5'-Oligoadenylate Synthetase / Q000097:blood; D000368:Aged; D001682:Biological Availability; D001707:Biopsy, Needle; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006207:Half-Life; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000493:pharmacokinetics* / Q000633:toxicity; D007677:Kidney Function Tests; D007680:Kidney Neoplasms / Q000097:blood* / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000473:pathology*; D009367:Neoplasm Staging; D019798:Neopterin / Q000097:blood; D009392:Nephrectomy / Q000379:methods; D011994:Recombinant Proteins; D018570:Risk Assessment; D015996:Survival Rate; D016896:Treatment Outcome
D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019798:Neopterin; D015088:2',5'-Oligoadenylate Synthetase